bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of the DNA repair gene O6-methylguanine—DNA methyltransferase by dexamethasone in glioblastomas
Authors: Ueda Shigeo , Mineta Toshihiro , Nakahara Yukiko , Okamoto Hiroaki , Shiraishi Tetsuya , Tabuchi Kazuo
Published: May 2009

Object.The DNA repair enzymeO6-methylguanine—DNA methyltransferase (MGMT) inhibits the cytotoxic effect of alkylating agents on tumor cells. The presence of two nonconsensus glucocorticoid-responsive elements in the humanMGMTpromoter region indicates the potential regulation of MGMT expression by glucocorticoid agents. This study was performed to elucidate whether dexamethasone affects the expression of MGMT in glioblastoma multiforme (GBM) cells, thereby limiting the benefit of chemotherapeutic alkylating agents.

Methods.Four GBM cell lines (A172, T98G, U138MG, and U87MG) were exposed to the alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) with or without dexamethasone. The expression levels ofMGMTwere correlated with the cytotoxic effects of ACNU in GBM cells. In the presence of ACNU alone, dexamethasone alone, and the combination of both agents, messenger RNA expression ofMGMTwas induced to varying degrees with the highest increases seen in the later conditions. This dexamethasone-dependent induction of theMGMTgene was even observed in U87MG cells in which the promoter is methylated, although the absolute expression ofMGMTmRNA was the lowest in that cell line. The induction ofMGMTby dexamethasone was associated with an increased resistance of these cells to ACNU.

Conclusions.These results indicate that dexamethasone-mediated upregulation ofMGMTlimits the efficiency of alkylating agents in the treatment of malignant gliomas.
Optimal blood glucose levels while using insulin to minimize the size of infarction in focal cerebral ischemia
Authors: Zhu Chang Z. , Auer Roland N.
Published: May 2009

Object. Insulin has been shown to ameliorate cerebral necrosis in global and, more recently, in focal cerebral ischemia. The goal of this study was to determine the relationship between this neuroprotective effect and blood sugar levels in a rat model of focal ischemia.

Methods. Thirty-four rats were subjected to 80 minutes of transient middle cerebral artery occlusion at a mean arterial blood pressure of 60 mm Hg and a temperature of 37°C. Insulin (3.5 IU/kg) was administered 1 hour before (12 rats) and 20 minutes after (12 rats) ischemia; 10 animals served as controls. A quantitative histopathological study conducted after 1 week of survival showed that insulin was not beneficial in reducing the size of the infarction or selective neuronal necrosis in the penumbra when administered before or after ischemia. In addition to infarction, six animals from the insulin-treated groups had bilateral selective neuronal necrosis in the hippocampus or the neocortex. A nonlinear regression analysis in which glucose levels were compared with both cortical necrosis and total infarction yielded a U-shaped curve with a nadir for cerebral necrosis that lay in the 6- to 7-mM blood glucose range. The increased brain damage induced by insulin occurred in animals with very low blood sugar values in the range of 2 to 3 mM.

Conclusions. These results in rats indicate that if insulin is used following ischemia, blood glucose levels should be maintained at approximately 6 to 7 mM. From these data one can infer that hypoglycemia of less than 3 mM should be avoided in situations of focal cerebral ischemia in which insulin is used. Additional animal studies and clinical trials in humans are needed to study the effects of insulin on ischemia.
Cerebral venous angioma of the pons complicated by nonhemorrhagic infarction
Authors: Peltier Johann , Toussaint Patrick , Desenclos Christine , Le Gars Daniel , Deramond Herve
Published: May 2009

✓ The authors emphasize an unusual complication of venous angiomas in the brain: venous infarction. The patient in this case is a 32-year-old man who presented with a clinical history of headache followed by a worsening of his neurological status. Neuroimaging studies demonstrated a brain infarct in the posterior fossa, which was related to thrombosis of the draining vein of a cerebral venous angioma. A conservative treatment approach without anticoagulation therapy was followed and the patient completely recovered. Nonhemorragic venous infarction caused by thrombosis of a venous angioma is exceptional and only nine previous cases have been reported in the literature.
Prophylactic administration of ceftriaxone for the prevention of meningitis after traumatic pneumocephalus: results of a clinical trial
Authors: Eftekhar Behzad , Ghodsi Mohammad , Nejat Farideh , Ketabchi Ebrahim , Esmaeeli Babak
Published: May 2009

Object. The purpose of this study was to compare the efficacy of the prophylactic use of ceftriaxone for the prevention of meningitis in patients with acute traumatic pneumocephalus.

Methods. In this prospective, single-institution, randomized clinical trial, 109 patients with mild head injury and traumatic pneumocephalus were randomly assigned to receive or not receive an antibiotic medication (ceftriaxone, 1 g given twice a day) until occurrence of meningitis or at least 5 days after trauma. The patients were followed up for 1 month posttrauma.

The 109 patients were divided into two groups: 53 were assigned to the prophylactic antibiotics therapy group and 56 to the control group. The overall rate of meningitis was 20.1% and the rates of meningitis in the two groups were not significantly different. The results were the same when adjusted for the patient's Glasgow Coma Scale score, sex, and age, as well as for an intradural location of air, air volume, presence of cerebrospinal fluid (CSF) rhinorrhea or CSF otorrhea, radiological sign of a skull base fracture, or intracranial hemorrhage.

Conclusions. The results of this study do not substantiate the efficacy of ceftriaxone used in the prevention of meningitis in patients with traumatic pneumocephalus after mild head injury or in any specific subgroup of these patients. Cerebrospinal fluid rhinorrhea and intracranial hemorrhage may be considered primary risk factors for the development of meningitis in patients with posttraumatic pneumocephalus and, in the absence of these symptoms, intradural location of air and air volume greater than 10 ml may be considered secondary risk factors. Further studies in this area are warranted.
Chorioretinal atrophy in a patient with moyamoya disease
Authors: Harissi-Dagher Mona , Sebag Mikael , Dagher Jehan H. , Moumdjian Robert
Published: May 2009

✓ Moyamoya disease is characterized by constrictions of segments of the internal carotid arteries (ICAs) and a resultant abnormal anastomotic network. In the literature, visual disturbances from cerebrovascular accidents in patients with moyamoya disease have been described, but very few reports of intraocular pathological conditions have been published. The authors describe a patient with moyamoya disease who presented with chorioretinal atrophy; an association between these two diseases has not previously been reported in the literature.

Findings of a clinical ophthalmological evaluation and angiographic series are presented. During the fundic examination, evidence of chorioretinal atrophy was found in this patient. Choroidal vascular insufficiency was revealed by intravenous fluorescein angiography and occlusion of the ICAs proximal to the origin of the posterior communicating arteries by selective carotid and vertebral arteriography. The vertebrobasilar system provided anastomotic connections via the posterior communicating arteries.

This is the first case report of chorioretinal atrophy associated with moyamoya disease. It is believed that the vasoocclusive effects of moyamoya disease may predispose the patient to atrophic changes in the peripheral retina. The development of an anastomotic network precludes the progression of this fundic anomaly.
A carcinoid tumor mimicking an isolated intracranial meningioma
Authors: Deshaies Eric M. , Adamo Matthew A. , Qian Jiang , DiRisio Darryl A.
Published: May 2009

✓ This 79-year-old woman presented with progressively worsening dementia, abulia, flat affect, urinary incontinence, and profuse watery diarrhea. Results of computerized tomography and magnetic resonance studies indicated an extraaxial, dural-based mass compressing the right frontal lobe and consistent with a convexity meningioma. A right frontal craniotomy was performed and the dural-based mass was resected. Histopathological features on immunostaining of the lesion were consistent with a carcinoid tumor (low-grade neuroendocrine carcinoma). Further evaluation revealed no primary carcinoid tumor in the foregut from which they typically originate. The authors concluded that this intracranial carcinoid tumor was the primary lesion despite its unusual location and that it should be included in the differential diagnosis of dural-based, extraaxial brain lesions.
Intracarotid Amytal memory test and hippocampal magnetic resonance imaging volumetry: validity of the Wada test as an indicator of hippocampal integrity among candidates for epilepsy surgery
Authors: Cohen-Gadol Aaron A. , Westerveld Michael , Alvarez-Carilles Juan , Spencer Dennis D.
Published: May 2009

Object. Intracarotid Amytal testing (the Wada test) has been used to lateralize language and identify patients who may be at risk for memory impairment after temporal lobectomy. The goal of this study was to determine the validity of the Wada test in the assessment of pathological conditions of the hippocampus among candidates for epilepsy surgery. The authors examined the correlation between the functional integrity of the hippocampus, measured using the Wada test, and quantitative measures of hippocampal pathology, determined by obtaining volumetric measurements of the hippocampus with the aid of magnetic resonance (MR) imaging.

Methods. The authors reviewed the relationship between memory scores on the Wada test and hippocampal volumes measured on preoperative MR images in 76 patients who underwent anteromedial temporal lobectomy and amygdalohippocampectomy for the treatment of medically refractory temporal lobe epilepsy. The data were analyzed with respect to their usefulness in lateralizing the seizure focus and predicting the long-term postoperative memory outcome.

Right and left hippocampal volume measurements did not correlate with one another (p > 0.1). Similarly, following a left carotid artery injection of Amytal the patients' right hemisphere memory was not significantly related to their left hemisphere memory on the Wada test (p > 0.1). On the other hand, the patients' right hemisphere memory significantly correlated with their right hippocampal volume (r = 0.51; p < 0.001) and their left hemisphere memory significantly correlated with their left hippocampal volume (r = 0.51; p < 0.001). Both right and left hemisphere memory scores correlated with the hippocampal volumetry ratio (r = 0.47 and r = 0.45, respectively; both p < 0.001). Lateralization of a seizure focus based on hippocampal volumetry results was significantly related to lateralization based on the results of the Wada test (r = 0.49; p < 0.01). The disparity between the Wada memory scores on ipsilateral and contralateral sides was significantly and inversely related to the change in verbal memory following temporal lobectomy (r = −0.28; p < 0.02). The preoperative hippocampal volumetry ratio also significantly and inversely correlated with the change in verbal memory after surgery (r = −0.31; p < 0.01).

Conclusions. The Wada memory test may be a valuable method of measuring the functional integrity of the hippocampus. The systematic study of MR imaging—acquired morphological data and Wada-acquired neuropsychological data may increase our understanding of the location of material-specific memory and the selection of eligible candidates for epilepsy surgery.
A patient-specific computer model to predict outcomes of the balloon occlusion test
Authors: Charbel Fady T. , Zhao Meide , Amin-Hanjani Sepideh , Hoffman William , Du Xinjian , Clark Marlyn E.
Published: May 2009

Object. Balloon occlusion tests (BOTs) are performed to identify patients who are at risk for ischemia and stroke following permanent internal carotid artery (ICA) occlusion. The object of this work was to determine whether patient-specific blood flow modeling can be used to identify patients in whom the BOT would not be tolerated.

Methods. The test was performed in 16 patients who underwent BOT with continuous neurological and electroencephalographic monitoring, followed by a hypotensive challenge. During hypotension a tracer was injected so that single-photon emission tomography (SPECT) scans could be obtained. Each individual brain circulation was modeled using information gained from phase-contrast magnetic resonance (MR) angiography and digital subtraction (DS) angiography, and the predicted effect of the BOT was evaluated.

Six patients did not tolerate the BOT; in these patients, decreases in middle cerebral artery (M1 segment) blood flow of 41 ± 27% (mean ± standard deviation), anterior cerebral artery (A3 segment) flow of 56 ± 33%, and posterior cerebral artery (P2 segment) flow of 4 ± 13% ipsilateral to the site of occlusion were found with modeling; these changes were significantly greater than the percentage of changes measured in the contralateral hemisphere (p < 0.05). Ten patients who tolerated the BOT well had calculated decreases in ipsilateral flows of only 9 ± 6% for the M1 segment, 12 ± 40% for the A3 segment, and 17 ± 21% for the P2 segment during BOT modeling.

Conclusions. A decrease in blood flow in both the ipsilateral M1 and A3 segments that was greater than 20%, calculated by flow modeling of the BOT, was 100% sensitive and 100% specific in identifying patients who could not tolerate the BOT. Blood flow modeling, coupled with DS angiography and noninvasive phase-contrast MR angiography measurements to make calculations patient specific, can be used to identify patients who have an elevated risk of ischemia during the BOT.
Role of apoptosis in intracranial aneurysm rupture
Authors: Pentimalli Luigi , Modesti Andrea , Vignati Andrea , Marchese Enrico , Albanese Alessio , Di Rocco Federico , Coletti Anna , Di Nardo Paolo , Fantini Cristina , Tirpakova Barbara , Maira Giulio
Published: May 2009

Object. Mechanisms involved in the rupture of intracranial aneurysms remain unclear, and the literature on apoptosis in these lesions is extremely limited. The hypothesis that apoptosis may reduce aneurysm wall resistance, thus contributing to its rupture, warrants investigation. The authors in this study focused on the comparative evaluation of apoptosis in ruptured and unruptured intracranial aneurysms. Peripheral arteries in patients harboring the aneurysms and in a group of controls were also analyzed.

Methods. Between September 1999 and February 2002, specimens from 27 intracranial aneurysms were studied. In 13 of these patients apoptosis was also evaluated in specimens of the middle meningeal artery (MMA) and the superficial temporal artery (STA). The terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling technique was used to study apoptosis via optical microscopy; electron microscopy evaluation was performed as well. Apoptotic cell levels were related to patient age and sex, aneurysm volume and shape, and surgical timing.

Significant differences in apoptosis were observed when comparing ruptured and unruptured aneurysms. High levels of apoptosis were found in 88% of ruptured aneurysms and in only 10% of unruptured lesions (p < 0.001). Elevated apoptosis levels were also detected in all MMA and STA specimens obtained in patients harboring ruptured aneurysms, whereas absent or very low apoptosis levels were observed in MMA and STA specimens from patients with unruptured aneurysms. A significant correlation between aneurysm shape and apoptosis was found.

Conclusions. In this series, aneurysm rupture appeared to be more related to elevated apoptosis levels than to the volume of the aneurysm sac. Data in this study could open the field to investigations clarifying the causes of aneurysm enlargement and rupture.
Immunohistochemical determination of the sympathetic pathway in the orbit via the cranial nerves in humans
Authors: Oikawa Susumu , Kawagishi Kyutaro , Yokouchi Kumiko , Fukushima Nanae , Moriizumi Tetsuji
Published: May 2009

Object. The present study was undertaken to elucidate the extent and precise distribution of the postganglionic sympathetic fibers in the cranial nerves projecting to the orbit and to reconstruct sympathetic routes in the orbit in humans. For this purpose, the authors made an immunohistochemical determination of the sympathetic fibers by using an antibody against norepinephrine-synthetic enzyme, tyrosine hydroxylase (TH).

Methods. Specimens containing the orbit and the cavernous sinus were obtained from formalin-fixed human cadavers. First, it was confirmed that the superior cervical ganglion contained strongly immunostained TH-positive neuronal cell bodies and fibers. After careful dissection of the cranial nerves projecting to the orbit, different segments of each cranial nerve were processed for immunohistochemical analysis for TH. All of the intraorbital cranial nerves contained TH-positive sympathetic fibers, although the amounts were very different in each cranial nerve. At the proximal site of the common tendinous ring, TH-positive fibers were found mainly in the abducent and trochlear nerves. At the distal site of this ring, TH-positive fibers were lost or markedly reduced in number in the abducent and trochlear nerves and were distributed mostly in the ophthalmic and oculomotor nerves. Among the cranial nerves projecting to the orbit, the ophthalmic nerve and its bifurcated nerves—frontal, lacrimal, and nasociliary—contained numerous TH-positive fibers.

Conclusions. The authors conclude that the postganglionic sympathetic fibers are distributed to all cranial nerves projecting to the orbit and that the ophthalmic nerve provides a major sympathetic route in the orbital cavity in humans.
Spontaneous regression of an aneurysm at a nonbranching site of the supraclinoid internal carotid artery
Authors: Ueta Takashi , Ichi Shunsuke , Ochi Takashi , Suzuki Ichiro
Published: May 2009

✓ The authors report on a patient who had presented with a subarachnoid hemorrhage whose bleeding source was not revealed on initial angiography, although subsequent studies disclosed a saccular aneurysm at a nonbranching site of the left internal carotid artery (ICA). The aneurysm could have been caused spontaneously or after blunt head trauma. The patient was supportively observed given the considerable risks associated with aggressive treatments. The present case represents the first involving spontaneous complete regression of an aneurysm at a nonbranching site of the supraclinoid ICA.
Preservation of hearing in patients undergoing microsurgery for vestibular schwannoma: degree of meatal filling
Authors: Mohr Gérard , Sade Burak , Dufour Jean-Jacques , Rappaport Jamie M.
Published: May 2009

Object. Preservation of hearing has become a standard goal in selected patients undergoing surgery for a vestibular schwannoma (VS). This study was aimed at analyzing the role played by filling of the internal auditory canal (IAC) as well as those played by preoperative hearing quality, and tumor size in the postoperative preservation of serviceable hearing (SH).

Methods. Three hundred eighty-six patients with VS were treated. Hearing preservation was attempted in 128 cases (33.2%) by using intraoperative monitoring and following a retrosigmoid approach. The maximal extrameatal size of the tumor, its extension within the IAC, and pre- and postoperative hearing quality, according to the Gardner—Robertson classification, were evaluated. Preservation of SH was achieved in 24.2% of the 128 patients. With respect to tumor size, SH was preserved in 39% of 77 patients harboring a tumor 15 mm wide or smaller and in 2% of 51 patients with lesions 16 mm wide or larger (p < 0.001). With regard to filling of the IAC, among 63 patients harboring a tumor 15 mm or smaller, in whom magnetic resonance images were available, SH was preserved in 52.8% of 36 patients with partial filling and in 25.9% of 27 patients with complete filling (p = 0.032). Concerning preoperative hearing quality, in the patients with tumors 15 mm or smaller, SH was preserved in 46.5% of 43 patients with Gardner—Robertson Class I hearing and 29.4% of 34 patients with Class II hearing (p = 0.126). Both tumor size and the extent of IAC filling proved statistically significant in a multivariable analysis (p < 0.001 and p = 0.026, respectively).

Conclusions. Incomplete filling of the IAC and a tumor size of 15 mm or smaller are independent favorable factors in SH preservation. Excellent preoperative hearing appears to have a positive impact but does not have statistical significance. Intraoperative monitoring is useful in guiding the dissection; however, the surgeon's knowledge of topographical landmarks and meticulous surgical technique remain the essential factors of success.
Meningiomas of the cerebellopontine angle with extension into the internal auditory canal
Authors: Roser Florian , Nakamura Makoto , Dormiani Mehdi , Matthies Cordula , Vorkapic Peter , Samii Madjid
Published: May 2009

Object. Only some meningiomas of the cerebellopontine angle (CPA) extend into the internal auditory canal (IAC) or arise from its dural lining. The authors investigated cases of CPA tumors in which the meningioma was inserted in the dura mater in or at the ICA or infiltrated a cranial nerve.

Methods. The authors reviewed patient charts including surgical and clinical records, intraoperative recordings of auditory evoked potentials, records of postoperative auditory examinations, and imaging studies.

In a series of 421 patients harboring CPA meningiomas, 72 patients in whom there was dural involvement of the IAC were investigated. Total tumor resection was achieved in 86.1%. In 34 patients, opening of the IAC was required for total tumor removal; this procedure did not influence the patient functional outcome. Among patients with secondary involvement of the IAC, anatomical preservation of the facial and cochlear nerves was obtained in 94%, whereas among patients in whom the lesion arose from the dura in or at the IAC these values were 80 and 75%, respectively. Functional preservation of the seventh and eighth cranial nerves in cases of tumor extension within the IAC was 86 and 77%, respectively, whereas in cases in which the IAC was involved it was only 60%. In four of five patients in whom the tumor had its origin in the dura mater within the IAC, the seventh or eighth cranial nerve had to be sacrificed to achieve tumor removal because of the lesion's infiltrative behavior. Facial nerve reconstruction by sural grafting was performed in the same operative procedure.

Conclusions. Meningiomas of the CPA involving the IAC require special surgical management. Dural involvement of the IAC requires opening by using a diamond drill, a procedure that does not influence cranial nerve outcome. The increased rate of cranial nerve morbidity is attributed to the infiltrative behavior of these meningiomas. If affected nerve segments have to be sacrificed, immediate reconstruction enables satisfactory long-term results.
Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size
Authors: Akagawa Hiroyuki , Kasuya Hidetoshi , Onda Hideaki , Yoneyama Taku , Sasahara Atsushi , Kim Chul-Jin , Lee Jung-Chung , Yang Tae-Ki , Hori Tomokatsu , Inoue Ituro
Published: May 2009

Object. Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations—Japanese and Korean.

Methods. The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with IAs and 214 Japanese and 191 Korean control volunteers. Differences in genotype frequencies among the various aneurysm sizes were evaluated using the Fisher exact test.

There was no significant difference in heterozygous (T/C) eNOS T-786C SNP between aneurysms 5 mm or smaller and those from 6 to 9 mm, and between lesions 5 mm or smaller and those 10 mm or larger in 336 Japanese patients harboring aneurysms—220 with ruptured and 116 with unruptured lesions—and in 191 Korean patients with ruptured aneurysms.

Conclusion. The eNOS T-786C SNP genotype does not influence the size of aneurysms.
Microsurgical anatomy of cerebral revascularization. Part II: Posterior circulation
Authors: Kawashima Masatou , Rhoton Albert L. , Tanriover Necmettin , Ulm Arthur J. , Yasuda Alexandre , Fujii Kiyotaka
Published: May 2009

Object. Revascularization is an important component of treatment for complex aneurysms, skull base tumors, and vertebrobasilar ischemia in the posterior circulation. In this study, the authors examined the microsurgical anatomy related to cerebral revascularization in the posterior circulation and demonstrate various procedures for bypass surgery.

Methods. The microsurgical anatomy of cerebral and cerebellar vessels as they relate to revascularization procedure and techniques, including extracranial-to-intracranial bypass grafting, arterial interposition grafting, and side-to-side anastomosis, were examined by performing stepwise dissections in 22 adult cadaveric specimens. The arteries and veins in the specimens were perfused with colored silicone.

Dominant cerebral and cerebellar revascularization procedures in the posterior circulations include superficial temporal artery (STA)—posterior cerebral artery (PCA), STA—superior cerebellar artery (SCA), occipital artery (OA)—anterior inferior cerebellar artery, OA—posterior inferior cerebellar artery (PICA), and PICA—PICA anastomoses. These procedures are effective in relatively small but critical areas including the brainstem and cerebellum. For revascularization of larger areas a saphenous vein graft is used to create a bypass between the PCA and the external carotid artery. Surgical procedures are generally difficult to perform in deep and narrow operative spaces near critical vital structures.

Conclusions. Although a clear guideline for cerebral revascularization procedures has not yet been established, it is important to understand various microsurgical techniques and their related anatomical structures. This will help surgeons consider surgical indications for treatment of patients with vertebrobasilar ischemia caused by aneurysms, tumors, or atherosclerotic diseases in the posterior circulation.
Cerebral vasospasm following intracranial hypotension caused by cerebrospinal fluid leak from an incidental lumbar durotomy
Authors: Chaves Claudia , Freidberg Stephen R. , Lee Grace , Zeris Vasilios , Ries Sarah , Chavali Ram
Published: May 2009

✓ The authors report on the unusual case of a patient with intracranial hypotension following an incidental durotomy complicated by an extensive but reversible cerebral vasospasm. Despite the dural tear repair and correction of the intracranial hypotension, the vasospasm ran its course. The precise mechanism of the cerebral vasospasm in this patient is unclear.
Discrepant findings for Wada test and functional magnetic resonance imaging with regard to language function: use of electrocortical stimulation mapping to confirm results
Authors: Kho Kuan H. , Leijten Frans S. S. , Rutten Geert-Jan , Vermeulen Jan , van Rijen Peter , Ramsey Nick F.
Published: May 2009

✓ The Wada test is still considered the gold standard for determining the language-dominant hemisphere prior to brain surgery. The authors report on a 34-year-old right-handed woman whose Wada test results indicated that the right hemisphere was dominant for language. In contrast, functional magnetic resonance (fMR) imaging was indicative of bilaterally represented language functions. Activation in the left hemisphere demonstrated on fMR imaging was most pronounced in the Broca area. Importantly, fMR imaging results in this area were confirmed on electrocortical stimulation mapping. These contradictory findings indicated that a right hemispherre dominance for language according to the Wada test should be questioned and verified using electrocortical stimulation. Nonetheless, the question remains whether involvement of these areas in the left frontal hemisphere is critical for language, as these were spared during surgery.
Risk factors for ischemic lesions following aneurysmal subarachnoid hemorrhage
Authors: Juvela Seppo , Siironen Jari , Varis Joona , Poussa Kristiina , Porras Matti
Published: May 2009

Object. The aim of this study was to test whether enoxaparin treatment (40 mg subcutaneously once daily) reduces the risk of cerebral infarction after subarachnoid hemorrhage (SAH) and to investigate predictive risk factors for permanent ischemic lesions visible on follow-up computerized tomography (CT) scans obtained 3 months after SAH.

Methods. After undergoing surgery for a ruptured aneurysm, 170 patients were randomized in a prospective, double-blind, placebo-controlled trial to test the effect of enoxaparin on the occurrence of ischemic lesions, which were demonstrated on follow-up CT scans available for 156 patients. The presence of lesions correlated highly with an impaired outcome, as assessed using both the Glasgow Outcome and modified Rankin Scales (p < 0.01). Lesions occurred in 101 (65%) of the 156 patients. In half of the patients (51 patients) no lesion was visible on the CT scan obtained on the 1st postoperative day in 51 patients. On univariate analysis, the presence of lesions at 3 months post-SAH was not associated with enoxaparin treatment but did correlate with several clinical, radiological, and prehemorrhage variables. Significant independent risk factors for lesions consisted of an impaired initial clinical condition (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.03–6.73), amount of subarachnoid blood (OR 6.51, 95% CI 2.27–18.65), nocturnal occurrence of SAH (that is, between 12:01 a.m. and 8:00 a.m.; OR 4.32, 95% CI 1.28–14.52), fixed symptoms of delayed ischemia (OR 5.21, 95% CI 1.02–26.49), duration of temporary artery occlusion during surgery (OR 1.66 per minute, 95% CI 1.20–2.31), and body mass index (OR 1.13/kg/m2, 95% CI 1.01–1.28).

Conclusions The presence of ischemic lesions can be predicted by the severity of bleeding, delayed cerebral ischemia, excess weight, duration of temporary artery occlusion, and occurrence of nocturnal aneurysm rupture.
Neurosurgical workforce trends in the United States
Authors: Gottfried Oren N. , Rovit Richard L. , Popp A. John , Kraus Kristin L. , Simon Arlene Stolper , Couldwell William T.
Published: May 2009

Object. The purpose of this study was to evaluate the US neurosurgery workforce by reviewing journal recruitment advertisements published during the past 10 years.

Methods. The number of available academic and private neurosurgical staff positions was determined based on recruitment advertisements in the Journal of Neurosurgery and Neurosurgery for the 10-year period from 1994 to 2003. Advertisements were evaluated for practice venue, subspecialization, and location. The numbers of active neurosurgeons and graduating residents also were reviewed.

The number of advertised neurosurgical positions increased from 141.6 ± 38.2 per year from 1994 through 1998 to 282.4 ± 13.6 per year from 1999 through 2003 (mean ± standard deviation, p < 0.05). The mean number of academic positions increased from 50.6 ± 11.1 to 95 ± 17.5 (p <0.05), and the mean number of private positions rose from 91 ± 30.4 to 187.4 ± 6.8 (p <0.05). Subspecialty positions represented a mean of only 15.6 ± 5% per year during the first time period and 18.8 ± 3% per year in the second period (p = 0.22), and therefore the majority of positions advertised continued to be those for generalists. The number of practicing neurosurgeons declined after 1998, and by 2002 it was less than it had been in 1991. The numbers of incoming and matriculating residents during the study period were static.

Conclusions. The number of recruitment advertisements for neurosurgeons during the last 5 years has increased significantly, concomitant with a severe decline in the number of active neurosurgeons and a static supply of residents.
Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line—derived neurotrophic factor
Authors: Slevin John T. , Gerhardt Greg A. , Smith Charles D. , Gash Don M. , Kryscio Richard , Young Byron
Published: May 2009

Object. Glial cell line-derived neurotrophic factor (GDNF) has demonstrated significant antiparkinsonian actions in several animal models and in a recent pilot study in England in which four of five patients received bilateral putaminal delivery. In the present study the authors report on a 6-month unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease (PD).

Methods. Patients with PD in a functionally defined on and off state were evaluated 1 week before and 1 and 4 weeks after intraputaminal catheter implantation in the side contralateral to the most affected side. Each patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 µg/day at successive 8-week intervals, followed by a 1-month wash-out period.

The Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off states significantly improved 34 and 33%, respectively, at 24 weeks compared with baseline scores (95% confidence interval [CI] 18–47% for off scores and 16–51% for on scores). In addition, UPDRS motor scores in both the on and off states significantly improved by 30% at 24 weeks compared with baseline scores (95% CI 15–48% for off scores and 5–61% for on scores). Improvements occurred bilaterally, as measured by balance and gait and increased speed of hand movements. All significant improvements of motor function continued through the wash-out period. The only observed side effects were transient Lhermitte symptoms in two patients.

Conclusions. Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion. Unilateral administration of the protein resulted in significant, sustained bilateral effects.
A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center
Authors: Kim Daniel H. , Murovic Judith A. , Tiel Robert L. , Moes Gregory , Kline David G.
Published: May 2009

Object. This is a retrospective review of 397 benign and malignant peripheral neural sheath tumors (PNSTs) that were surgically treated between 1969 and 1999 at the Louisiana State University Health Sciences Center (LSUHSC). The surgical techniques and adjunctive treatments are presented, the tumors are classified with respect to type and prevalence at each neuroanatomical location, and the management of malignant PNSTs is reviewed.

Methods. There were 361 benign PNSTs (91%). One hundred forty-one benign lesions were brachial plexus tumors: 54 schwannomas (38%) and 87 neurofibromas (62%), of which 55 (63%) were solitary neurofibromas and 32 (37%) were neurofibromatosis Type 1 (NF1)—associated neurofibromas. Among the brachial plexus lesions supraclavicular tumors predominated with 37 (69%) of 54 schwannomas; 34 (62%) of 55 solitary neurofibromas; and 19 (59%) of 32 NF1-associated neurofibromas. One hundred ten upper-extremity benign PNSTs consisted of 32 schwannomas (29%) and 78 neurofibromas (71%), of which 45 (58%) were sporadic neurofibromas and 33 (42%) were NF1-associated neurofibromas. Twenty-five benign PNSTs were removed from the pelvic plexus. Lower-extremity PNSTs included 32 schwannomas (38%) and 53 neurofibromas (62%), of which 31 were solitary neurofibromas and 22 were NF1-associated neurofibromas.

There were 36 malignant PNSTs: 28 neurogenic sarcomas and eight other sarcomas (fibro-, spindle cell, synovial, and perineurial sarcomas).

Conclusions. The majority of tumors were benign PNSTs from the brachial plexus region. Most of the benign PNSTs in all locations were neurofibromas, with sporadic neurofibromas predominating. Similar numbers of schwannomas were found in the upper and lower extremities, whereas neurofibromas were more prevalent in the upper extremities. Despite aggressive limb-ablation or limb-sparing surgery plus adjunctive therapy, malignant PNSTs continue to be associated with high morbidity and mortality rates.
Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13—PE38QQR for recurrent malignant glioma
Authors: Parney Ian F. , Kunwar Sandeep , McDermott Michael , Berger Mitchel , Prados Michael , Cha Soonmee , Croteau David , Puri Raj K. , Chang Susan M.
Published: May 2009

Object.Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13—PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncatedPseudomonasexotoxin. Serial neuroradiographic changes were assessed in this cohort of patients.

Methods.Patients were treated in two groups: Group 1 patients received IL13—PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13—PE38QQR, patients were followed up without instituting new antitumor therapy.

Conclusions.As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.
Posterior petrous meningiomas: 82 cases
Authors: Wu Zhe Bao , Yu Chun Jiang , Guan Shu Sen
Published: May 2009

Object. The aim of this study was to discuss posterior petrous meningiomas—their classification, clinical manifestations, surgical treatments, and patient outcomes.

Methods. A retrospective analysis was performed in 82 patients with posterior petrous meningiomas for microsurgery. According to the anatomical relationship with the posterior surface of the petrous bone and with special reference to the internal auditory canal (IAC), posterior petrous meningiomas were classified into three types: Type I, located laterally to the IAC (28 cases); Type II, located medially to the IAC, which might extend to the cavernous sinus and clivus (32 cases); and Type III, extensively attached to the posterior surface of the petrous bone, which might envelop the seventh and eighth cranial nerves (22 cases).

Sixty-eight (83%) of 82 cases involved total resection. The rate of anatomical preservation of facial nerve was 97.5%, whereas the functional preservation rate was 81%. The rate of hearing preservation was 67%. All Type I tumors were completely resected, and the rate of anatomical preservation of facial nerve was 100% and functional preservation was 93%. Regarding Type II lesions, 75% of 32 cases involved total resection; the rate of anatomical preservation of facial nerve was 97% and functional preservation was 75%. For Type III lesions, 73% of 22 cases were totally resected. The rate of anatomical preservation of facial nerve in patients with this tumor type was 95%, whereas functional preservation was 73%.

Conclusions. Clinical manifestations and surgical prognoses are different among the various types of posterior petrous meningiomas. It is more difficult for Types II and III tumors to be resected radically than Type I lesions, and postoperative functional outcomes are significantly worse accordingly. The primary principles in dealing with this disease entity include preservation of vital vascular and central nervous system structures and total resection of the tumor as much as possible.
Intraoperative power Doppler ultrasonography with a contrast-enhancing agent for intracranial tumors
Authors: Kanno Hiroshi , Ozawa Yukihiko , Sakata Katsumi , Sato Hidemitsu , Tanabe Yutaka , Shimizu Nobuyuki , Yamamoto Isao
Published: May 2009

Object. The goal of this study was to evaluate intraoperative power Doppler ultrasonography when used with a contrast-enhancing agent for operations on intracranial tumors.

Methods. Forty intracranial tumors were examined using power Doppler ultrasonography with a galactose micro-particle—based ultrasonographic contrast-enhancing agent during operations on the brain. The tumors included 37 intracranial neoplasms (14 gliomas, six meningiomas, three hemangioblastomas, two malignant lymphomas, three other primary neoplasms, nine metastatic tumors, and three nonneoplastic lesions). All patients also underwent computerized tomography and magnetic resonance imaging, and all but three of the patients underwent digital subtraction (DS) angiography. Before injection of the ultrasonographic contrast agent, intra- and peritumoral power Doppler flow signals were detected in 32 of the intracranial tumors. After the injection, the signals were enhanced in blood vessels around the tumors and in the tumor parenchyma in 36 tumors. The duration of contrast enhancement continued for 70 to 365 seconds (mean 251.8 ± 69 seconds) after the injection. Among the tumors, hemangioblastomas displayed particularly strong contrast enhancement. In these intracranial tumors, the echo signals obtained using contrast-enhanced power Doppler ultrasonography correlated with DS angiographic staining. Power Doppler ultrasonograms with the appropriate contrast agent provided better data on the precise real-time position of the tumors and their relationship to adjacent vessels than ultrasonograms obtained before the injection of the contrast agent.

Conclusions. Intraoperative power Doppler ultrasonography performed using a contrast-enhancing agent can facilitate intraoperative real-time navigation and assessment of the intratumoral vasculature and peritumoral vessels, particularly for tumors having abundant vessels such as hemangioblastomas.
Multimodal metabolic imaging of cerebral gliomas: positron emission tomography with [18F]fluoroethyl-l-tyrosine and magnetic resonance spectroscopy
Authors: Floeth Frank Willi , Pauleit Dirk , Wittsack Hans-Jörg , Langen Karl Josef , Reifenberger Guido , Hamacher Kurt , Messing-Jünger Martina , Zilles Karl , Weber Friedrich , Stummer Walter , Steiger Hans-Jakob , Woebker Gabriele , Müller Hans-Wilhelm , Coenen Heinz , Sabel Michael
Published: May 2009

Object. The purpose of this study was to determine the predictive value of [18F]fluoroethyl-l-tyrosine (FET)—positron emission tomography (PET) and magnetic resonance (MR) spectroscopy for tumor diagnosis in patients with suspected gliomas.

Methods. Both FET-PET and MR spectroscopy analyses were performed in 50 consecutive patients with newly diagnosed intracerebral lesions supposed to be diffuse gliomas on contrast-enhanced MR imaging. Lesion/brain ratios of FET uptake greater than 1.6 were considered positive, that is, indicative of tumor. Results of MR spectroscopy were considered positive when N-acetylaspartate (NAA) was decreased in conjunction with an absolute increase of choline (Cho) and an NAA/Cho ratio of 0.7 or less. An FET lesion/brain ratio, an NAA/Cho ratio, and signal abnormalities on MR images were compared with histological findings in neuronavigated biopsy specimens.

The FET lesion/brain ratio and the NAA/Cho ratio were identified as significant independent predictors for the histological identification of tumor tissue. The accuracy in distinguishing neoplastic from nonneoplastic tissue could be increased from 68% with the use of MR imaging alone to 97% with MR imaging in conjunction with FET-PET and MR spectroscopy. Sensitivity and specificity for tumor detection were 100 and 81% for MR spectroscopy and 88 and 88% for FET-PET, respectively. Results of histological studies did not reveal tumor tissue in any of the lesions that were negative on FET-PET and MR spectroscopy. In contrast, a tumor diagnosis was made in 97% of the lesions that were positive with both methods.

Conclusions. In patients with intracerebral lesions supposed to be diffuse gliomas on MR imaging, FET-PET and MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted biopsies.
Biological activity of adult cavernous malformations: a study of 56 patients
Authors: Sure Ulrich , Freman Sandra , Bozinov Oliver , Benes Ludwig , Siegel Adrian M. , Bertalanffy Helmut
Published: May 2009

Object.Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions.

Methods.The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and endoglin antibodies.

Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB-1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1α in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.

Conclusions.The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.