bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor efficacy improved by local delivery of species-specific endostatin
Authors: Huszthy Peter C. , Brekken Christian , Pedersen Tina B. , Thorsen Frits , Sakariassen Per Øystein , Skaftnesmo Kai Ove , Haraldseth Olav , Lønning Per Eystein , Bjerkvig Rolf , Enger Per Øyvind
Published: January 2008

Object

Conflicting results have been reported concerning the antitumor efficacy of the angiogenesis inhibitor endostatin. This may be due to differences in the biological distribution of endostatin between studies or to the varying biological efficacies of the different protein forms that were examined. To address this issue, the authors used a local delivery approach in which each tumor cell secreted endostatin, providing uniform endostatin levels throughout the tumors. This allowed a direct assessment of the biological efficacy of soluble endostatin in vivo.

Methods

The authors genetically engineered BT4C gliosarcoma cells so that they would stably express and secrete either the human or murine form of endostatin. Endostatin-producing cells or mock-infected cells were implanted intracerebrally in syngeneic BD-IX rats. The antitumor efficacy of endostatin was evaluated on the basis of survival data and tumor volume comparisons. In addition, microvascular parameters were assessed.

The authors confirmed the continuous release of endostatin by the BT4C cells. A magnetic resonance imaging–assisted comparison of tumor volumes revealed that local production of murine endostatin significantly inhibited tumor growth. Notably, 40% of the animals in this treatment group experienced long-term survival without histologically verifiable tumors 7 months after cell implantation. After local treatment with murine endostatin, tumor blood plasma volumes were reduced by 71%, microvessel density counts by 84%, and vascular area fractions by 75%. In contrast, human endostatin did not inhibit tumor growth significantly in this model. Centrally located regions of necrosis were present in tumors secreting both the human and the murine species-specific form of endostatin.

Conclusions

The results suggest that endostatin inhibits tumor angiogenesis in vivo in a species-specific manner.
Reduced expression of the transporter associated with antigen processing 1 molecule in malignant glioma cells, and its restoration by interferon-γ and -β
Authors: Satoh Eiji , Mabuchi Tadashi , Satoh Hiroki , Asahara Takayuki , Nukui Hideaki , Naganuma Hirofumi
Published: January 2008

Object

It remains unclear whether malignant glioma cells can deliver tumor antigens efficiently to major histocompatibility complex (MHC) Class I molecules. To elucidate the mechanism of antigen presentation in malignant gliomas, the authors examined the expression of the transporter associated with antigen processing 1 (TAP1), which transports antigens to MHC Class I molecules, and low-molecular-mass polypeptide 2 (LMP2), which is a subunit of a proteasome. They also analyzed the effects of interferon (IFN)-γ and IFN-β on the expression of these molecules.

Methods

Five glioma cells expressed undetectable or very low levels of TAP1 protein and did not express TAP1 messenger (m)RNA. Normal brain tissue and glioma tissue specimens also showed undetectable levels of TAP1 protein and the same levels of LMP2 protein as lymphoblastoid B cells. Treatments of the tumor cells with IFN-γ or -β enhanced the expression of both TAP1 protein and mRNA as well as the expression of MHC Class I molecules. The expression of LMP2 protein was not altered by the IFN treatments. The authors analyzed structural alterations in the TAP1 promoter region in eight malignant glioma cell lines. Single nucleotide polymorphism was found in 446 bp upstream of the translation start site of the TAP1 gene, and a point mutation was found in 34 bp upstream of the TAP1 gene.

Conclusions

Malignant glioma cells may be less immunogenic due to low levels of TAP1 expression. Upregulated expression of TAP1 and MHC Class I molecules by IFN-γ and -β may enhance antigen presentation in malignant glioma cells.
Episodic nocturnal wandering in a patient with epilepsy due to a right temporoinsular low-grade glioma: relief following resection
Authors: Duffau Hugues , Kujas Michèle , Taillandier Luc
Published: January 2008

✓ Although controversial, episodic nocturnal wandering (ENW) is thought to be a rare and atypical form of nocturnal epilepsy, originating in the frontal lobe and responsive to antiepileptic drugs (AEDs). The authors report the case of a patient harboring a right temporoinsular low-grade glioma, who presented with a 3-year history of agitated somnambulent episodes resistant to AEDs. Interestingly, the ENW totally resolved after tumor resection and the patient reported no recurrence during a follow-up period of 4.5 years. To the authors’ knowledge, this is the first report of ENW due to a glioma; the findings support the theory that ENW may represent an unusual type of lesional epilepsy that is surgically correctable. Moreover, a temporoinsular origin of ENW can now be considered.
The impact of genotype on outcome in oligodendroglioma: validation of the loss of chromosome arm 1p as an important factor in clinical decision making
Authors: Kanner Andrew A. , Staugaitis Susan M. , Castilla Elias A. , Chernova Olga , Prayson Richard A. , Vogelbaum Michael A. , Stevens Glen , Peereboom David , Suh John , Lee Shih-Yuan , Tubbs Raymond R. , Barnett Gene H.
Published: January 2008

Object

Oligodendrogliomas are rare primary brain tumors. They comprise approximately 5 to 33% of all glial tumors but differ from astrocytomas by being associated with a more favorable prognosis, making their correct identification important. Allelic loss of chromosome arms 1p and 19q is found in a substantial subpopulation of tumors with an oligodendroglioma phenotype. Anaplastic oligodendrogliomas with allelic loss of 1p have been associated with chemosensitivity and a longer patient survival period.

Methods

Oligodendroglial neoplasms were studied using fluorescence in situ hybridization of formalin-fixed, paraffin-embedded tissue specimens; reference and target probe sets were used to map the telomeric regions of 1p and 19q. The results were correlated with the clinical characteristics of patients treated at our institution between 1993 and 2003.

Data obtained in 96 patients were analyzed. This included 63 patients (65.6%) with World Health Organization (WHO) Grade II oligodendroglioma, 22 (23%) with Grade III oligodendroglioma, and 11 (11.4%) with mixed oligoastrocytoma. Analysis of 1p in patients with pure oligodendroglioma revealed a loss of 1p in 42 patients (49.4%). In 46 of these patients 19q was lost and in 70 (82.3%) there was concordance for combined loss or retention of both 1p and 19q (p < 0.0001). Patients with oligodendroglioma in whom a loss of 1p was present fared significantly better, and this outcome was unrelated to the treatment modality or WHO grade, compared with patients in whom 1p was intact (p < 0.05).

Conclusions

To the authors’ knowledge, this study includes the largest published series of WHO Grade II oligodendroglioma and 1p analysis. The results suggest that the association between long-term survival and 1p loss in oligodendroglioma is unrelated to treatment. The authors of further prospective studies may better determine the true value of the allelic loss of 1p and its implication for clinical decision making.
Intraorbital implantation of a stimulating electrode for an optic nerve visual prosthesis
Authors: Brelén Mårten E. , De Potter Patrick , Gersdorff Michel , Cosnard Guy , Veraart Claude , Delbeke Jean
Published: January 2008

✓Research into visual prosthetics is expected to revolutionize the treatment of blind patients with incurable outer retinal degenerative disease. Substantial evidence shows that useful visual sensations can be produced by controlled electrical stimulation of the optic nerve. To make the optic nerve visual prosthesis more acceptable, implantation techniques safer and less invasive than those previously used have been developed. A medial transconjunctival approach is now used to implant a stimulating electrode around the intraorbital section of the optic nerve. This new technique allows sufficient exposure of the nerve after detaching only one rectus muscle and performing a lateral canthotomy. Previously, an electrode was implanted in the intracranial part of the optic nerve, which required more invasive surgery. The new technique was first developed in cadavers and in patients undergoing eye enucleations. Finally, a 68- year-old blind man suffering from retinitis pigmentosa underwent long-term implantation. In this case report the authors describe the technique and outline some of the challenges involved.
Cranial surgery with an expanded compact intraoperative magnetic resonance imager
Authors: Schulder Michael , Salas Sussan , Brimacombe Michael , Fine Peter , Catrambone Jeffrey , Maniker Allen H. , Carmel Peter W.
Published: January 2008

✓In this article the authors report the implementation of an expanded compact intraoperative magnetic resonance (iMR) imager that is designed to overcome significant limitations of an earlier unit.

The PoleStar N20 iMR imager has a stronger magnetic field than its predecessor (0.15 tesla compared with 0.12 tesla), a wider gap between magnet poles, and an ergonomically improved gantry design. The additional time needed in the operating room (OR) for use of iMR imaging and the number of sessions per patient were recorded. Stereotactic accuracy of the integrated navigational tool was assessed using a water-covered phantom.

Of the 55 patients who have undergone surgery in the PoleStar N20 device, diagnoses included glioma in 13, meningioma in 12, pituitary adenoma in nine, other skull base lesions in seven, and miscellaneous other diagnoses. The extra time required for use of the system averaged 1.1 hours (range 0.5–2 hours). Imaging sessions averaged 2.3 per surgery (range one–six sessions).

Measurement of stereotactic accuracy revealed that T1-weighted images were the most accurate. Thinner slices yielded measurably greater accuracy, although this was of questionable clinical significance (all sequences ≤ 4 mm had a mean error of ≤ 1.8 mm). The position of the phantom in the center compared with the periphery of the magnetic field did not affect accuracy (mean error 0.9 mm for each).

The PoleStar N20 appears to make intraoperative neuroimaging with a low-field-strength magnet much more practical than it was with the first-generation device. Greater ease of positioning resulted in a decrease in added time in the OR and encouraged a larger number of imaging sessions.
Predominance of cellular edema in traumatic brain swelling in patients with severe head injuries
Authors: Marmarou Anthony , Signoretti Stefano , Fatouros Panos P. , Portella Gina , Aygok Gunes A. , Bullock M. Ross
Published: January 2008

Object

The edema associated with brain swelling after traumatic brain injury (TBI) has been thought to be vasogenic in origin, but the results of previous laboratory studies by the authors have shown that a cellular form of edema is mainly responsible for brain swelling after TBI. In this study the authors used magnetic resonance (MR) imaging techniques to identify the type of edema that occurs in patients with TBI.

Methods

Diffusion-weighted MR imaging was used to evaluate the apparent diffusion coefficient (ADC) in 44 patients with TBI (Glasgow Coma Scale Score < 8) and in eight healthy volunteers. Higher ADC values have been associated with vasogenic edema, and lower ADC values with a predominantly cellular form of edema. Regional measurements of ADC in patients with focal and diffuse injury were computed. The water content of brain tissue was also assessed in absolute terms by using MR imaging to measure the percentage of water per gram of tissue. Cerebral blood flow (CBF) was measured using stable Xe–computerized tomography (CT) studies to rule out ischemia as a cause of cellular edema.

The mean ADC value in the healthy volunteers was 0.82 ± 0.05 × 10−3 mm2/second. The ADC values in the patients with diffuse brain injury without swelling were close to the mean for the healthy volunteers. In contrast, the patients with brain swelling had increased brain water content and low ADC values (mean 0.74 ± 0.05 × 10−3 mm2/second). The ADC values correlated with CT classifications. In all patients with low ADC values, the CBF values were outside the range for ischemia.

Conclusions

The brain swelling observed in patients with TBI appears to be predominantly cellular, as signaled by low ADC values in brain tissue with high levels of water content.
Predictive value of initial computerized tomography scan, intracranial pressure, and state of autoregulation in patients with traumatic brain injury
Authors: Hiler Magdalena , Czosnyka Marek , Hutchinson Peter , Balestreri Marcella , Smielewski Peter , Matta Basil , Pickard John D.
Published: January 2008

Object

The authors explored the relationship between computerized tomography (CT) scan findings and intracranial pressure (ICP) measurements obtained in the first 24 hours of monitoring to identify parameters predicting outcome in patients with severe traumatic brain injury (TBI).

Methods

Intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure (CPP), and pressure reactivity index were measured continuously in 126 patients with severe TBI who were admitted to a neuroscience critical care unit. Mean values in the initial 24 hours of monitoring and in the total period of monitoring were compared with types of injury categorized on the basis of the initial CT scan according to the classification of Marshall, et al., and with Glasgow Outcome Scale scores.

The initial CT scan classification correlated significantly but weakly with ICP measured during the first 24 hours of monitoring (p = 0.036) but not with mean ICP over the total time of intensive care. Both midline shift and the ratio of frontal horn diameter to internal diameter correlated with ICP in the first 24 hours (p < 0.007) and with ICP over the total monitoring period (p < 0.03). Outcome score correlated with initial CT scan findings (p = 0.018), ICP over the total monitoring period (p < 0.0023), pressure reactivity over the total monitoring period (p < 0.0002), and pressure reactivity in the first 24 hours (p < 0.0001) but not with ICP in the first 24 hours. Patients with disturbed pressure reactivity in the first 24 hours after injury had a significantly higher mortality rate than patients with intact pressure reactivity (28.6% compared with 9.5%; p < 0.001).

Conclusions

Patients with severe TBI who have early loss of autoregulation have a worse prognosis. Mean ICP values in patients with diffuse TBI cannot be predicted by using the Marshall CT scan classification.
Bruns syndrome caused by intraventricular neurocysticercosis treated using flexible endoscopy
Authors: Torres-Corzo Jaime , Vecchia Roberto Rodriguez-Della , Rangel-Castilla Leonardo
Published: January 2008

Object

Neurocysticercosis is the most frequent cause of hydrocephalus in adults in regions where the disease is endemic, including Latin America. The prognosis for intraventricular neurocysticercosis is worse than that for the intraparenchymal form of the disease, making treatment especially important. Although active and viable intraventricular cysts produce no reaction in the host, they can cause noncommunicating hydrocephalus, whose onset is frequently abrupt. Sometimes the increasing intracranial pressure due to obstruction of the cerebral aqueduct (ball-valve mechanism) is intermittent, producing relapsing/remitting symptoms; this life-threatening phenomenon is called “Bruns syndrome.”

Methods

Between 1996 and 2004, among a group of 285 patients with neurocysticercosis and Bruns syndrome caused by cysticercal cysts of the third ventricle was diagnosed in seven patients by using magnetic resonance imaging. An endoscopic procedure with a flexible cerebral endoscope was performed, intact parasitic cysts were removed, and a complete exploration was undertaken to look for more cysticercal cysts in the whole ventricular system and the subarachnoid basal cisterns. There were no deaths or complications. All seven patients were asymptomatic during a follow-up period ranging from 1 to 5 years.

Conclusions

Flexible cerebral endoscopy allows one, in a minimally invasive manner, to approach the ventricular system and subarachnoid basal cisterns and to remove intraventricular neurocysticercal cysts. Flexible endoscopy is an alternative treatment for Bruns syndrome caused by neurocysticercosis of the third ventricle.
Superficial peroneal nerve syndrome: an unusual nerve entrapment
Authors: Yang Lynda J. S. , Gala Vishal C. , McGillicuddy John E.
Published: January 2008

✓Lower-extremity pain and paresthesia have multiple origins. Early recognition of the symptoms of peripheral nerve entrapment leads to timely treatment and avoids the cost of unnecessary studies. The authors report on a case of superficial peroneal nerve syndrome resulting from nerve herniation through a fascial defect, which was responsive to surgical treatment.

This 22-year-old man presented with pain and paresthesias over the lateral aspect of the right calf and the dorsum of the foot without motor weakness. Exercise led to the formation of a tender bulge approximately 12 cm above the lateral malleolus. Percussion of this site worsened his symptoms. Radiography and electromyography studies were nondiagnostic. The patient underwent surgical decompression that involved division of the fascia overlying the nerve and neurolysis of the superficial peroneal nerve. The operation resulted in symptom-free relief.

Superficial peroneal nerve syndrome is an entrapment neuropathy that results from mechanical compression of the nerve at or near the point where the nerve pierces the fascia to travel within the subcutaneous tissue. Surgical decompression of the mechanical entrapment usually provides relief from pain and paresthesia.
Intraneural perineurioma of the third cranial nerve: occurrence and identification
Authors: Almefty Rami , Webber Bruce L. , Arnautović Kenan I.
Published: January 2008

✓Intraneural perineurioma is a true but rare neoplasm that originates from perineurial cells and mainly affects peripheral nerves. It must be distinguished from other hypertrophic neuropathies that are either inflammatory or demonstrate an onion-bulb formation that originates from Schwann cells. Complying with this strict definition, only three additional cases of cranium-related perineurioma have been identified: two lesions arose extracranially and involved cranial nerves, and one occurred intracranially but did not involve a nerve.

The authors describe a 27-year-old woman who presented with left third cranial nerve palsy and was found to harbor a mass lesion in the superior orbital fissure and cavernous sinus. After subtotal resection had been performed, pathological studies confirmed the presence of perineurial tumor cells in a pseudo–onion bulb formation. The cells stained positively for epithelial membrane antigen but not for S100 protein, clearly distinguishing the disease from one that originates in Schwann cells.
Glioblastoma multiforme with diffusion-weighted magnetic resonance imaging characteristics mimicking primary brain lymphoma
Authors: Toh Cheng-Hong , Chen Yao-Liang , Hsieh Tsung-Che , Jung Shih-Ming , Wong Ho-Fai , Ng Shu-Hang
Published: January 2008

✓ The authors report on the first case of corpus callosum glioblastoma multiforme (GBM) with diffusion-weighted (DW) magnetic resonance (MR) imaging findings that mimicked those for lymphoma but with MR spectroscopy results absent of lymphoma characteristics. This 68-year-old man presented with rapid, progressive impairment in short-term memory as well as slow responses and a change in his personality within 3 weeks of admission. Results of cranial computed tomography revealed a slightly hyperdense corpus callosum tumor with bihemispheric involvement. Magnetic resonance images showed a homogeneous mass with strong enhancement. The mass showed water restriction on DW MR images and apparent diffusion coefficient (ADC) maps but no markedly elevated lipid resonance on MR spectroscopy. The patient underwent tumor resection. Results of pathological studies with immunohistochemical analysis confirmed that the lesion was GBM.

Diffusion-weighted MR imaging together with ADC mapping and MR spectroscopy was reported to be useful in differentiating GBM and primary brain lymphoma. The lymphomas were hyperintense to gray matter on DW MR images and isointense to hypointense on ADC maps because of water restriction. In contrast, the GBMs were hyperintense to gray matter on both DW MR images and ADC maps because of the T2 shine-through effect. On MR spectroscopy, lipid resonance was markedly elevated in lymphoma but only slightly elevated in GBM.
Surgical shunt infection: significant reduction when using intraventricular and systemic antibiotic agents
Authors: Ragel Brian T. , Browd Samuel R. , Schmidt Richard H.
Published: January 2008

Object

Infection represents the most common serious complication of shunt surgery, and typically its incidence ranges between 5 and 15%, despite the use of systemic antibiotic agents. Because systemic antibiotic medications generally penetrate the cerebrospinal fluid (CSF) poorly, the authors investigated, in a controlled study, whether the addition of intraventricular antibiotic treatment decreases the incidence of perioperative infection in adult patients.

Methods

Data pertaining to all CSF shunt procedures conducted at the authors’ institution during an 11-year period were reviewed. Perioperative infection was defined as culture-positive CSF and the clinical presence of infection-related symptoms occurring within 90 days of surgery. All patients underwent intraoperative systemic antistaphylococcal antibiotic therapy. Before May 16, 1999, the senior author (R.H.S.) also administered 4 mg of gentamicin intraventricularly at surgery (Group I); thereafter, 10 mg of vancomycin was additionally administered (Group II). Other neurosurgeons at this institution did not use intraventricular antibiotic therapy, and their patients served as additional controls in identical time periods (Groups III and IV).

A total of 802 shunt procedures were performed in 534 patients. Control infection rates were 5.4% (eight of 147) in Group I; 6.2% (nine of 145) in Group III; and 6.7% (18 of 267) in Group IV. With the combination of systemic antibiotic and intraventricular gentamicin and vancomycin (Group II), the infection rate fell significantly to 0.4% (one of 243). No complications were noted in association with intraventricular antibiotic administration.

Conclusions

The combination of intraventricular gentamicin and vancomycin with systemic antibiotic therapy significantly decreased the incidence of perioperative shunt infection. It is presumed that intraventricular antibiotic therapy extends prophylactic antibiotic coverage into the CSF and prevents bacterial seeding.
Tako-tsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage: an underappreciated ventricular dysfunction
Authors: Lee Vivien H. , Connolly Heidi M. , Fulgham Jimmy R. , Manno Edward M. , Brown Robert D. , Wijdicks Eelco F. M.
Published: January 2008

Object

Neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage (SAH) is associated with a wide spectrum of reversible left ventricular wall motion abnormalities and includes a subset of patients with a pattern of apical akinesia and concomitant sparing of basal segments called “tako-tsubo cardiomyopathy.”

Methods

After obtaining institutional review board approval, the authors retrospectively identified among all patients admitted to the Mayo Clinic’s Neurological Intensive Care Unit between January 1990 and January 2005 those with aneurysmal SAH who had met the echocardiographic criteria for tako-tsubo cardiomyopathy. Among 24 patients with SAH-induced reversible cardiac dysfunction, the authors identified eight with SAH-induced tako-tsubo cardiomyopathy. All eight patients were women with a mean age of 55.5 years (range 38.6–71.1). Seven patients presented with a poor-grade SAH, reflected by a Hunt and Hess grade of III or IV. Four patients underwent aneurysm clip application, and four underwent endovascular coil occlusion. The initial mean ejection fraction (EF) was 38% (range 25–55%), and the mean EF at recovery was 55% (range 40–68%). Cerebral vasospasm developed in six patients, but cerebral infarction developed in only three patients.

Conclusions

The authors describe the largest cohort with aneurysmal SAH–induced tako-tsubo cardiomyopathy. In the SAH population, tako-tsubo cardiomyopathy predominates in postmenopausal women and is often associated with pulmonary edema, prolonged intubation, and cerebral vasospasm. Additional studies are warranted to understand the complex mechanism involved in tako-tsubo cardiomyopathy and its intriguing relationship to neurogenic stunned myocardium.
Concurrent lymphocytic hypophysitis and pituitary adenoma
Authors: Moskowitz Shaye I. , Hamrahian Amir , Prayson Richard A. , Pineyro Mercedes , Lorenz Robert R. , Weil Robert J.
Published: January 2008

✓Lymphocytic hypophysitis (LyH) is an uncommon intrasellar lesion characterized by lymphocytic infiltration of the adenohypophysis. Evidence suggests that the cause is autoimmune, and the symptoms are usually related to either a mass effect or endocrine dysfunction. Lymphocytic hypophysitis has been described rarely in the setting of other simultaneous pathological processes that involve the pituitary and sella turcica, and is postulated to arise from an intrinsic inflammatory response.

The authors report the case of a 43-year-old woman who presented with a 2-month history of galactorrhea and pseudohyperprolactinemia secondary to a 10-mm lesion within an enlarged pituitary gland. She was nulliparous and had no contributory medical history. Serial neuroimaging performed over a 2-year period demonstrated lesion growth, and visual deficits had developed; together these warranted surgical intervention. A transsphenoidal resection was performed. Microscopic and immunohistopathological examinations revealed a nonsecreting pituitary adenoma with concurrent lymphocytic adenohypophysitis.

This is the first documented case of LyH in the setting of a null-cell pituitary adenoma. The authors review the related literature and outline potential mechanisms for the concurrent development of LyH and a pituitary adenoma.
The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms
Authors: Pannu Hariyadarshi , Kim Dong H. , Guo Dongchuan , King Terri M. , Van Ginhoven Grace , Chin Toinette , Chang Katherine , Qi Yuhua , Shete Sanjay , Milewicz Dianna M.
Published: January 2008

Object

Matrix metalloproteinases (MMPs) are a family of endopeptidases that mediate vascular remodeling by degrading extracellular matrix components, such as collagen and elastin. On the basis of accumulating evidence that implicates increased MMP-2 (gelatinase A) and MMP-9 (gelatinase B) amounts and activity in the pathogenesis of aneurysms, the authors investigated the genetic association between polymorphisms in MMP-2 and MMP-9 and sporadic intracranial aneurysms.

Methods

Eight polymorphisms located in MMP-2 and MMP-9 were genotyped, and the association of these variations with disease was assessed in a Caucasian population consisting of 125 patients with intracranial aneurysms and 234 ethnically matched healthy volunteers.

Polymorphisms in the MMP-2 gene and the haplotypes generated from these polymorphisms were not associated with the occurrence of intracranial aneurysms. However, a polymorphism located in the 3′ untranslated region of MMP-9 showed a significant association with disease in the study population, with individuals carrying the TT genotype at increased risk for developing intracranial aneurysms (odds ratio 1.91, p = 0.005). Haplotypes containing the T allele of this polymorphism also showed a comparable association with disease. Similar results were obtained in an analysis of these polymorphisms in a subgroup of patients who presented with ruptured aneurysms.

Conclusions

The study findings support a role for MMP-9, but not MMP-2, in the pathogenesis of intracranial aneurysms.
Focal disruption of the blood–brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery
Authors: Hynynen Kullervo , McDannold Nathan , Vykhodtseva Natalia , Raymond Scott , Weissleder Ralph , Jolesz Ferenc A. , Sheikov Nickolai
Published: January 2008

Object

The goal of this study was to explore the feasibility of using low-frequency magnetic resonance (MR) image–guided focused ultrasound as a noninvasive method for the temporary disruption of the blood–brain barrier (BBB) at targeted locations.

Methods

Rabbits were placed inside a clinical 1.5-tesla MR imaging unit, and sites in their brains were targeted for 20-second burst sonications (frequency 260 kHz). The peak pressure amplitude during the burst varied between 0.1 and 0.9 MPa. Each sonication was performed after an intravenous injection of an ultrasound contrast agent (Optison). The disruption of the BBB was evaluated with the aid of an injection of an MR imaging contrast agent (MAG-NEVIST). Additional tests involving the use of MION-47, a 20-nm magnetic nanoparticle contrast agent, were also performed. The animals were killed at different time points between 3 minutes and 5 weeks postsonication, after which light or electron microscopic evaluation was performed.

The threshold for BBB disruption was approximately 0.2 MPa. More than 80% of the brain sites sonicated showed BBB disruption when the pressure amplitude was 0.3 MPa; at 0.4 MPa, this percentage was greater than 90%. Tissue necrosis, ischemia, and apoptosis were not found in tissue in which the pressure amplitude was less than 0.4 MPa; however, in a few areas of brain tissue erythrocytes were identified outside blood vessels following exposures of 0.4 MPa or higher. Survival experiments did not show any long-term adverse events.

Conclusions

These results demonstrate that low-frequency ultrasound bursts can induce local, reversible disruption of the BBB without undesired long-term effects. This technique offers a potential noninvasive method for targeted drug delivery in the brain aided by a relatively simple low-frequency device.
Long-term response of pituitary carcinoma to temozolomide
Authors: Fadul Camilo E. , Kominsky Andrew L. , Meyer Louise P. , Kingman Linda S. , Kinlaw William B. , Rhodes C. Harker , Eskey Clifford J. , Simmons Nathan E.
Published: January 2008

✓Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma.

One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone–secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy.

Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.
Peroneal neuropathy following successful bariatric surgery
Authors: Elias W. Jeffrey , Pouratian Nader , Oskouian Rod J. , Schirmer Bruce , Burns Ted
Published: January 2008

✓Peroneal neuropathy has been observed in starvation, anorexia, and other situations of extreme weight loss. The authors report a case in which sequential bilateral peroneal neuropathies developed after successful bariatric surgery resulting in a weight loss of 114 lbs over 12 months. The diagnosis was confirmed using nerve conduction studies and electromyography. Clinical improvement occurred with decompressive surgery at the level of the knee.
Percutaneous transvenous embolization of a dural arteriovenous fistula through a mastoid emissary vein
Authors: Rivet Dennis J. , Goddard James K. , Rich Keith M. , Derdeyn Colin P.
Published: January 2008

✓ Definitive endovascular treatment of dural arteriovenous fistulas (DAVFs) requires obliteration of the site of the fistula: either the diseased dural sinus or the pial vein. Access to this site is often limited by occlusion of the sinus proximal and distal to the segment containing the fistula. The authors describe a technique in which the mastoid emissary vein is used to gain access to a Borden–Shucart Type II DAVF in the transverse–sigmoid sinus. Recognition of this route of access, if present, may facilitate endovascular treatment of these lesions. Access to the transverse sinus via this approach can be straightforward and may be underused.
Linear accelerator radiosurgery for vestibular schwannomas
Authors: Friedman William A. , Bradshaw Patrick , Myers Adam , Bova Frank J.
Published: January 2008

Object

Radiosurgery has become a popular treatment for small vestibular schwannomas (VSs). The aim of this study was to review an extensive, single-institution experience with linear accelerator (LINAC) radiosurgery for VSs.

Methods

Between July 1988 and August 2005, 390 patients with VSs were treated with LINAC–based radiosurgery at the authors’ institution. Patient and treatment variables were prospectively maintained in a computer database. Outcomes were tracked through periodic clinical examinations and annual scanning studies. Multivariate and actuarial statistics were used to analyze rates of local tumor control and complications, including facial and trigeminal neuropathies, after treatment.

One- and 2-year actuarial control rates were both 98%, and the 5-year actuarial control rate was 90%. Only four patients (1%) required surgery for tumor growth. Seventeen patients (4.4%) reported facial weakness and 14 patients (3.6%) reported facial numbness after radiosurgery. The risk of these complications rose with increasing tumor volume or increasing radiosurgical dose to the tumor periphery. Since 1994, when doses were deliberately lowered to 1250 cGy, only two patients (0.7%) have experienced facial weakness and two (0.7%) have experienced facial numbness.

Conclusions

Radiosurgery provides a safe and effective therapeutic alternative to surgery for small VSs.
Jugular tubercle: morphometric analysis and surgical significance
Authors: Mintelis Apostolos , Sameshima Tetsuro , Bulsara Ketan R. , Gray Linda , Friedman Allan H. , Fukushima Takanori
Published: January 2008

Object

Maximizing intradural exposure via the extreme lateral infrajugular transcondylar–transtubercular exposure (ELITE) approach depends on understanding the fundamental anatomy of the jugular tubercle (JT). Drilling the JT can maximize the extent of exposure achieved with the ELITE approach. Removing the JT is critical for optimizing access to the inferior and midclival areas, vertebrobasilar artery junction, and ventral pons and medulla.

Methods

In this cadaveric study, the individual structural variations in the JT were evaluated in 100 split occipital bones. The mean length of the JT was 1.65 ± 0.36 cm (range 1.2–3 cm); its mean width was 1.15 ± 0.16 cm (range 0.7–1.7 cm); and its mean thickness was 0.61 ± 0.15 cm (range 0.2–1 cm). The authors analyzed the difference in morphometric data with regard to right and left sides and found no statistically significant difference between the two sides. Furthermore, data from the morphometric study were compared with the results of 20 measurements obtained from three-dimensional computed tomography (3D CT) scans. Accordingly, the mean length of the JT was 1.35 ± 0.15 cm (range 1–2.8 cm); the mean width, 1.10 ± 0.12 cm (range 0.8–1.3 cm); and the mean thickness, 0.51 ± 0.18 cm (range 0.2–1 cm).

Conclusions

Morphometric data on the JT contribute significantly to the neurosurgeon’s task of skull base drilling. The 3D CT scans were useful in the preoperative planning.
Treatment of vertebral artery aneurysms with transposition of the posterior inferior cerebellar artery to the vertebral artery combined with parent artery occlusion
Authors: Ogasawara Kuniaki , Kubo Yoshitaka , Tomitsuka Nobuhiko , Sasoh Masayuki , Otawara Yasunari , Arai Hiroshi , Ogawa Akira
Published: January 2008

✓ The authors describe transposition of the posterior inferior cerebellar artery (PICA) to the vertebral artery (VA) combined with parent artery occlusion for the treatment of VA aneurysms in cases in which a clip could not be applied because of the origin of the ipsilateral PICA. The aneurysm is trapped through a lower lateral suboccipital craniectomy. The PICA is then cut just distal to the aneurysm, and the PICA and VA proximal to the aneurysm are anastomosed in an end-to-end or end-to-side fashion.

The surgical procedure was successfully performed in two patients, each of whom had hypoplastic occipital arteries (OAs). The PICA contralateral to the lesion was hypoplastic in one patient and distant to the ipsilateral PICA in the other patient. Mild transient dysphagia developed postoperatively in one patient due to glossopharyngeal and vagus nerve palsy, and the other patient had an uneventful postoperative course. In both patients, postoperative cerebral angiography demonstrated good patency of the transposed PICA. These results show that transposition of the PICA to the VA is a useful procedure for the reconstruction of the PICA when parent artery occlusion is necessary to exclude a VA aneurysm involving the origin of the PICA and when OA–PICA anastomosis or PICA–PICA anastomosis cannot be performed.
Neuroanatomy and cadaver dissection in Italy: history, medicolegal issues, and neurosurgical perspectives
Authors: Frati Paola , Frati Alessandro , Salvati Maurizio , Marinozzi Silvia , Frati Riccardo , Angeletti Luciana Rita , Piccirilli Manolo , Gaudio Eugenio , Delfini Roberto
Published: January 2008

✓ Despite the significant Italian tradition of important anatomical studies, an outdated law historically influenced by the Catholic church restricts the use of cadavers for teaching and scientific purposes. The object of the present paper was to trace the historical evolution of the Italian anatomical tradition, particularly neuroanatomical studies, in relation to the juridical regulations on the use of cadavers today. Special attention was paid to the opportunities offered to neurosurgery by using cadavers and to the scientific and social issues in neurosurgical training in the twenty-first century. Considering the new Common European Constitution, the authors advocate a political solution from the European community to improve the quality of training in the disciplines with a social impact such as neurosurgery.
Systemic metabolic effects of combined insulin-like growth factor–I and growth hormone therapy in patients who have sustained acute traumatic brain injury
Authors: Hatton Jimmi , Kryscio Richard , Ryan Melody , Ott Linda , Young Byron
Published: January 2008

Object

Hypermetabolism, hypercatabolism, refractory nitrogen wasting, hyperglycemia, and immunosuppression accompany traumatic brain injury (TBI). Pituitary dysfunction occurs, affecting growth hormone (GH) and plasma insulin-like growth factor–I (IGF-I) concentrations. The authors evaluated whether combination IGF-I/GH therapy improved metabolic and nutritional parameters after moderate to severe TBI.

Methods

The authors conducted a prospective, randomized, double-blind study comparing combination IGF-I/GH therapy and a placebo treatment. Ninety-seven patients with TBI were enrolled in the study within 72 hours of injury and were assigned to receive either combination IGF-I/GH therapy or placebo. All patients received concomitant nutritional support. Insulin-like growth factor–I was administered by continuous intravenous infusion (0.01 mg/kg/hr), and GH (0.05 mg/kg/day) was administered subcutaneously. Placebo control group patients received normal saline solution in place of both agents. Nutritional and metabolic monitoring continued throughout the 14-day treatment period.

The two groups did not differ in energy expenditure, nutrient intake, or use of insulin treatment. The mean daily serum glucose concentration was higher in the treatment group (123 ± 24 mg/dl) than in the control group (104 ± 11 mg/dl) (p < 0.03). A positive nitrogen balance was achieved within the first 24 hours in the treatment group and remained positive in that group throughout the treatment period (p < 0.05). This pattern was not observed in the control group. Plasma IGF-I concentrations were above 350 ng/ml in the treatment group throughout the study period. Overall, the mean plasma IGF-I concentrations were 1003 ± 480.6 ng/ml in the treatment group and 192 ± 46.2 ng/ml in the control group (p < 0.01).

Conclusions

The combination of IGF-I and GH produced sustained improvement in metabolic and nutritional endpoints after moderate to severe acute TBI.
Minimally invasive implantation of the peritoneal catheter in ventriculoperitoneal shunt placement for hydrocephalus: analysis of data in 151 consecutive adult patients
Authors: Bani Alan , Telker Dieter , Hassler Werner , Grundlach Matthias
Published: January 2008

Object

The authors report on their experience with laparoscopy-guided implantation of a peritoneal catheter in ventriculoperitoneal shunt placement procedures in adults.

Methods

In performing the conventional method of shunt placement in 2001, 8% of the cases resulted in malposition and dislocation of the distal catheter; therefore, the authors together with personnel from the Department of General Surgery decided to utilize an interdisciplinary approach involving laparoscopy-guided implantation of the catheter. Between October 2001 and January 2005, 202 ventriculoperitoneal shunt placement procedures were conducted in adult patients for hydrocephalus of various origins.

In 152 patients, laparoscopy-guided implantation of the distal catheter was performed. In all except one of these patients, implantation was successful. Laparoscopy and the cranial part of the surgery were performed simultaneously. There was an 8% rate of malposition of the distal catheter in the nonlaparoscopy group. In contrast, there was no dislocation or malposition of the distal catheter in the laparoscopy group. Two cases (1.3%) of shunt infection occurred in the laparoscopy group.

Conclusions

Laparoscopic implantation of a distal catheter is a simple, minimally invasive, and easy procedure to perform and allows exact localization of the peritoneal catheter and confirmation of its patency.
Long-term electrical stimulation–induced inhibition of partial epilepsy
Authors: Elisevich Kost , Jenrow Ken , Schuh Lori , Smith Brien
Published: January 2008

✓The aim of this study was to determine the effects of long-term continuous cerebrocortical electrical stimulation in the treatment of partial epilepsy. The authors review the case of a 44-year-old man with medically intractable postencephalitic localization-related epilepsy with ictal onset in the primary motor cortex. For 5 years he was treated using patterned subthreshold electrical stimulation of the ictal site. This therapy has successfully eliminated the jacksonian march of cortical excitability and secondary generalization and reduced seizure frequency and intensity with an immediate postictal return of motor function. Over time, the seizure frequency subsided by more than 90%, with the patient showing no adverse features resulting from focal stimulation.

The results in this case support the hypothesis that effective and safe long-term modulation of focal epilepsy is possible with focal cerebrocortical electrical stimulation.
Midterm outcomes of paclitaxel-eluting stents for the treatment of intracranial posterior circulation stenoses
Authors: Steinfort Brendan , Ng Perry P. , Faulder Kenneth , Harrington Timothy , Grinnell Verity , Sorby William , Morgan Michael K.
Published: January 2008

Object

Symptomatic intracranial vertebral and basilar artery atherosclerotic stenoses carry a high risk of stroke and permanent disability if refractory to maximal medical therapy. The authors conducted a study to determine the technical feasibility and midterm clinical and angiographic outcomes in patients in whom paclitaxel-eluting stents were placed for the treatment of symptomatic intracranial posterior circulation stenoses.

Methods

A retrospective review of medical records and imaging studies was performed for 13 consecutive patients in whom paclitaxel-coated stents were used to treat symptomatic posterior circulation intracranial stenoses between 2002 and 2005. Clinical follow-up data were supplemented by telephone interviews.

The technical success rate for stent placement was 100%. One patient (8%) suffered a periprocedural stroke. Twelve patients (92%) underwent clinical follow up for a minimum of 3 months postsurgery, and 11 (92%) of these patients remained asymptomatic after a mean period of 10.9 months. Nine patients (69%) underwent catheter angiographic follow up, and no patient had significant in-stent recurrence of stenosis after a mean period of 5.4 months.

Conclusions

Treatment of intracranial posterior circulation stenoses with drug-eluting stents is technically feasible, and the rate of clinically significant periprocedural complications is low. Rates of stenosis recurrence are reduced compared with those of bare-metal stents in the midterm. Midterm clinical outcome is excellent; no symptom recurrence was observed in this patient cohort.