廣瀬 雄一

Management of gliomas depends on histological diagnosis; there are, however, limitations to the systems presently used. Tumors in the same entity can have different clinical courses, especially when they are diagnosed as WHO grade II-III. Previous studies revealed that genetic subgrouping of gliomas provides useful information that could help establishment of treatment procedures on the basis of the genetic background of the tumors. Recently, the authors analyzed the chromosomal copy number aberrations (CNAs) of adult supratentorial gliomas by comparative genomic hybridization using microdissected tissue sections. The tumors were classified into subgroups according to chromosomal CNAs. WHO grade II-III gliomas contained a variety of genetic subgroups that correlated well with the clinical course. Of these, long progression-free survival was observed for tumors with +7q and those with -1p/19q, low-grade tumors of 2 major lineages, and, in our preliminary data, both were closely correlated with mutation of IDH1. Furthermore, in contrast with +7q tumors, the great majority of +7 or +7/-10q groups had wildtype IDH1. Genetic studies suggest that cytogenetic characterization may provide an additional classification system for gliomas, and new criteria could help to establish rational and objective means for analysis of treatment procedures.

Stereotactic biopsy has been validated for tissue sampling of deep-seated lesions that cannot be easily resected via open craniotomy. However, some inherent problems including the inability to directly observe the lesion and difficulty in confirming hemostasis limit its usefulness. To overcome these issues, we used the endoscope in brain tumor biopsy, for not only intraventricular tumors but also intraparenchymal tumors. The rigid scope was used in association with a surgical navigation system for intraparenchymal lesions via a transcortical route. There were no useful anatomical landmarks when the trajectory to the lesions was decided; therefore, surgical navigation system was required for the transcortical procedures. The endoscopic procedure described here was attempted in 21 cases of intraparenchymal lesions between January 2007 and February 2012. A definitive diagnosis was obtained in all cases, and genetic analysis was performed when required. Serious postsurgical hemorrhage or neurological deficits were not observed in any cases. Endoscopic surgery provides a clear view of the target and makes it easier to differentiate tumor tissue from normal brain tissue. Moreover, the endoscope helped to confirm hemostasis during the procedure. Thus, endoscopic biopsy has the potential to contribute toward safe and reliable diagnosis of brain tumors.

Chronic subdural haematoma (CSDH) is an uncommon but potentially serious complication of clipping unruptured cerebral aneurysms. We conducted a study to identify the patients who are at risk of developing postoperative CSDH. The data from 713 consecutive patients who underwent clipping of unruptured anterior circulation aneurysms were reviewed, and risk factors correlated with CSDH were identified by multivariate regression analysis of demographic variables. Fifteen patients (2.1%) developed CSDH after the surgery. Advanced age (odds ratio [OR] 1.151, 95% confidence interval [CI] 1.051-1.261) and male gender (OR 3.167, 95% CI 1.028-9.751) were correlated with CSDH. Subsequently, all 713 patients were quadrichotomized on the basis of gender and age, with 70 years as the cut-off value for age. The frequency of CSDH in men <70 years of age was 1.3% and that in men 70 years of age was 15.1%, with risk of CSDH was significantly higher in the older men (OR 13.39; 95% CI: 3.42-52.44). The frequency of CSDH in women <70 years of age was 0.6% and that in women >= 70 years of age was 3.7%. As in men, the risk of CSDH was significantly higher in the older women (OR 6.69, 95% CI 1.10-40.73). The interval between the aneurysm clipping and CSDH development was 0.5-6 months, suggesting that clinical observation should be continued up to 6 months after surgery. Although prognosis for patients with a. postoperative CSDH complication is generally favourable, the risk of CSDH should be taken into account when considering elective clipping of unruptured aneurysms in patients >= 70 years of age. (C) 2012 Elsevier Ltd. All rights reserved.

A rare case of ancient schwannoma originating from subfrontal region is reported. A 39-year-old woman underwent a medical checkup of the brain and her magnetic resonance imaging revealed a well-circumscribed mass with cystic change in the left subfrontal region. H-1 magnetic resonance spectroscopy, positron emission tomography, and perfusion computed tomography failed to reveal any malignant findings. Total removal of the tumor by subfrontal approach was performed. Pathologic evaluation revealed strongly suggestive findings of ancient schwannoma, a rare variant of schwannoma. Subfrontal schwannoma is uncommon; especially, that with ancient change is further rare, and, herein, its neuroradiologic and histologic features are discussed.

Seizures occurring after clipping of unruptured cerebral aneurysms have rarely been documented in the literature. The objective of this retrospective study is to clarify whether the frequency of early seizures, i.e., seizures occurring within 14 days of surgery, is influenced by patient- or aneurysm-specific characteristics. Data on 1,000 consecutive patients who underwent clipping of unruptured anterior circulation aneurysms were reviewed. They consisted of 387 men and 613 women with mean age of 59.8 ± 9.7 years. Fifty-one patients (5.1 %) developed early seizures. Interestingly, the frequency was similar to that occurring after clipping of unruptured posterior circulation aneurysms (n = 20, 5.0 %). Multivariate regression analysis revealed that younger age was correlated with early seizures (odds ratio (OR) 0.902 95 % confidence interval (CI) 0.891-0.989). However, other variables, including aneurysm size and operation length, were not correlated. Although patients with history of epilepsy exhibited relatively high frequency of early seizures, the difference was not statistically significant. The frequency was unaffected by location or multiplicity of aneurysms. Thirty-one patients (61 %) developed seizures within 24 h of clipping. Regarding seizure types, 34 (67 %) developed generalized seizures and the other 17 (33 %) experienced partial seizures. Patients with generalized seizures were significantly more likely to harbor an iatrogenic brain lesion than those with partial seizures (47 vs. 18 % OR 4.148 95 % CI 1.005-17.113). Among 40 patients with follow-up period &gt 12 months, seizures were temporary without recurrence in 38 (95 %). Although early seizures are mostly benign, a small possibility of them becoming a permanent morbidity needs to be explained to patients undergoing elective clipping. © 2013 Springer-Verlag Berlin Heidelberg.

Cancers metastatic to the skull or dura may cause subdural hematoma (SDH). However, the frequency is low, and the presence of underlying cancers has almost always been known in such situations. We report a case of skull angiosarcoma manifesting as SDH, posing a diagnostic challenge to physicians. A 75-year-old man visited our clinic with sensorimotor disturbance of gradual onset approximately 1 month after a minor head trauma. He was diagnosed with SDH after imaging studies, and underwent surgery to evacuate the hematoma. Because the hematoma was organized, surgery was switched from burr-hole drainage to craniotomy. The bone flap as well as the dura over the hematoma had grossly normal appearance, and only the hematoma itself was submitted for histological examination. Although postoperative recovery was uneventful, the patient experienced recurrence of the SDH 2 months after surgery. At the second surgery, the bone flap and dura were intermingled with tumor tissue, and histological examination revealed that an epithelioid angiosarcoma originating from the skull was responsible for the SDH. Timely diagnosis of angiosarcoma manifesting as SDH is difficult because of its rarity. In retrospect, however, the diagnosis might have been established earlier if the bone flap and/or the dura had been biopsied at the time of the first surgery. The present case gives us a lesson that SDH may be an unusual manifestation of malignant tumors of skull or dural origin, and histological examination of not only hematoma capsule but also of the surrounding tissues may provide important diagnostic clues. © 2012 Springer Science+Business Media, LLC.

Patients with aneurysmal subarachnoid hemorrhage (SAH) are frequently complicated by acute cardiac dysfunctions, including cardiac wall motion abnormality (WMA). Massive release of catecholamine into the systemic circulation after aneurysmal rupture is believed to result in WMA, and poor-grade SAH seems to be the most important risk factor. However, plasma catecholamine levels have rarely been measured in SAH patients with WMA, and previous studies indicated that the elevated levels might not necessarily predict WMA. The objective of this study is (1) to evaluate relationship between WMA and plasma catecholamine levels in poor-grade SAH patients in the acute phase and (2) to clarify clinical characteristics of SAH patients with WMA. Among 142 poor-grade (World Federation of Neurosurgical Societies grades IV and V) SAH patients, 48 underwent both transthoracic ultrasound and measurement of plasma catecholamine levels within 24 h of SAH onset. They were divided into WMA+ (n = 23) and WMA- (n = 25) groups, and intergroup comparison was made on demographics, plasma catecholamine levels, and outcomes. Plasma norepinephrine levels were significantly higher in WMA+ group than in WMA- group (2,098.4 +/- 1,773.4 vs. 962.9 +/- 838.9 pg/mL, p = 0.02), and the former showed significantly worse outcomes 90 days after admission. There were no intergroup differences in the plasma levels of epinephrine. Plasma norepinephrine levels were inversely correlated with left ventricular ejection fraction. Multivariate logistic regression analysis revealed that increased plasma norepinephrine levels were predictive of WMA, although age, female sex, and grade V SAH were not. This retrospective study highlights the role of norepinephrine in pathogenesis of SAH-induced WMA.

BACKGROUND: For cardiac arrest (CA) victims, brain computed tomography (CT) may serve as a prognosticator. Loss of gray-white matter discrimination (GWMD) and sulcal edema/effacement are reliable CT signs of hypoxia, and a time window may exist for development of these signs. Most data are derived from CA victims of cardiac etiology, however, and CT signs have rarely been evaluated in victims of CA secondary to subarachnoid hemorrhage (SAH). METHODS: A retrospective study was conducted to clarify the incidence, temporal profile, and prognostic significance of early CT signs in resuscitated SAH-CA patients. RESULTS: During a 6-year period, 35 SAH-CA patients were identified. CT signs were observed in 94 %: loss of GWMD was observed in 94 %, whereas sulcal edema/effacement was observed in 77 %. In 29 patients, the interval between CA and the return of spontaneous circulation (ROSC) was estimated. CT signs developed almost invariably when the CA-ROSC interval exceeded 10 min. Loss of GWMD always preceded sulcal edema/effacement. None of the 35 patients achieved long-term survival, regardless of the presence of the CT signs. CONCLUSION: CT signs may develop earlier in patients with SAH-CA than CA of cardiac origin. Because of a poor prognosis, early CT signs are not useful prognosticators in that population.

The outcomes of patients with traumatic cardiac arrest (TCA) have been dismal. However, imaging modalities are improving rapidly and are expected to play a role in treatment of patients with TCA. In this retrospective study, whether obtaining computed tomography (CT) immediately after resuscitation had any clinical value was evaluated. Among 145 patients with TCA admitted to our institution during 4 years, hemodynamically stable return of spontaneous circulation (ROSC) was achieved in 38 (26%). Brain and cervical spine CT was obtained prospectively, and the frequency and type of traumatic brain injury (TBI)/upper cervical spine injury (UCSI) were investigated. CT was performed uneventfully in all patients with an average door-to-CT time of 51.5 ± 18.6 min. Twenty (53%) had CT evidence of TBI. However, no patients underwent brain surgery because of lack of return of brainstem functions. Among the 18 patients without TBI, CT signs of hypoxia were present in 15 patients (39%), and CT was considered intact in 3 patients (8%). None of the 35 patients with abnormal CT findings survived, and the presence of such findings predicted fatality with high sensitivity and specificity. While 13 of the 38 patients (34%) had CT evidence of UCSI, concomitant TBI and USCI were uncommon. None of the 13 patients with UCSI underwent spine surgery because of lack of return of brainstem functions, and the presence of USCI might also be associated with fatality. Although obtaining CT was useful in the prognostication of TCA patients with ROSC, it did not have much impact in therapeutic decision making. © 2013 by The Japan Neurosurgical Society.

Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH. Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly. Seven patients (11 %) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE- group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE- group (324.6 +/- 172.8 vs 163.1 +/- 257.2 pg/ml, p = 0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6 +/- 2034.5 vs 847.9 +/- 535.6 pg/ml, p < 0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95 % CI, 1.002-1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R = 0.48, p < 0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000 pg/ml, with an area under the curve value of 0.85. Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.

Aim: Ground-level fall is the most common cause of traumatic intracranial hemorrhage (TICH) in the elderly, and is a major cause of morbidity and mortality in that population. A retrospective study was carried out to evaluate whether the use of warfarin/low-dose aspirin (LDA) is predictive of unfavorable outcomes in geriatric patients who sustain a fall-induced TICH. Methods: Charts of 76 geriatric patients (=65 years-of-age) with fall-induced TICH were reviewed. The number of patients taking warfarin and LDA was 12 and 21, respectively, whereas the other 43 took neither medication (non-user group). The frequency of patients with unfavorable outcomes (Glasgow Outcome Scale score of 13) at discharge was calculated. Furthermore, variables predictive of unfavorable outcomes were identified by logistic regression analysis. Results: The frequency of patients with unfavorable outcomes was 75% in the warfarin group, 33% in the LDA group and 27% in the non-user group, respectively. The risk of having unfavorable outcomes was significantly higher in the warfarin group compared with the LDA group (P = 0.03) and non-user group (P < 0.01). Logistic regression analysis showed that variables predictive of unfavorable outcomes were: age, initial Glasgow Coma Scale score = 13 and presence of midline shift = 5 mm. Conclusion: The use of warfarin, but not of LDA, might be associated with unfavorable outcomes in elderly with fall-induced TICH. The risk of TICH should be communicated properly to elderly taking warfarin. The information might be important not only to trauma surgeons who take care of injured elderly, but also to geriatric physicians who prescribe warfarin/LDA to them. Geriatr Gerontol Int 2012; 12: 667-672.

Aim: Ground-level fall is the most common cause of traumatic intracranial hemorrhage (TICH) in the elderly, and is a major cause of morbidity and mortality in that population. A retrospective study was carried out to evaluate whether the use of warfarin/low-dose aspirin (LDA) is predictive of unfavorable outcomes in geriatric patients who sustain a fall-induced TICH. Methods: Charts of 76 geriatric patients (=65 years-of-age) with fall-induced TICH were reviewed. The number of patients taking warfarin and LDA was 12 and 21, respectively, whereas the other 43 took neither medication (non-user group). The frequency of patients with unfavorable outcomes (Glasgow Outcome Scale score of 13) at discharge was calculated. Furthermore, variables predictive of unfavorable outcomes were identified by logistic regression analysis. Results: The frequency of patients with unfavorable outcomes was 75% in the warfarin group, 33% in the LDA group and 27% in the non-user group, respectively. The risk of having unfavorable outcomes was significantly higher in the warfarin group compared with the LDA group (P = 0.03) and non-user group (P < 0.01). Logistic regression analysis showed that variables predictive of unfavorable outcomes were: age, initial Glasgow Coma Scale score = 13 and presence of midline shift = 5 mm. Conclusion: The use of warfarin, but not of LDA, might be associated with unfavorable outcomes in elderly with fall-induced TICH. The risk of TICH should be communicated properly to elderly taking warfarin. The information might be important not only to trauma surgeons who take care of injured elderly, but also to geriatric physicians who prescribe warfarin/LDA to them. Geriatr Gerontol Int 2012; 12: 667-672.

A 71-year-old woman presented with a rare case of geriatric ependymoma originating from the fourth ventricle manifesting as progressive gait and memory disturbance. Imaging studies revealed an extraaxial mass in the fourth ventricle protruding into the right cerebellomedullary cistern, with concomitant obstructive hydrocephalus. Surgery achieved subtotal removal since the tumor tightly adhered to the right vestibular area of the fourth ventricular floor. The histological diagnosis was ependymoma, which was also confirmed by comparative genetic hybridization. Although she developed severe laryngeal edema and worsening of the hydrocephalus postoperatively which required additional treatment, she recovered with residual mild gait disturbance, and was transferred to a rehabilitation facility. Fourth ventricle ependymoma in the elderly is rare. Comparative genetic hybridization may be important in the diagnosis of geriatric ependymoma and in the choice for adjuvant therapy as well as in estimating the prognosis for patients with rare types of ependymoma.

Background and Purpose-The majority of patients with ventricular wall motion abnormality (WMA) associated with subarachnoid hemorrhage (SAH) are postmenopausal women. In addition to elevated catecholamine, the role of estrogen in the pathogenesis of WMA has recently been implicated. The objective of this study is to clarify the interrelation among catecholamine, estrogen, and WMA in patients with SAH. Methods-A retrospective analysis was performed on the medical records of 77 patients with SAH (23 men, 54 women) whose plasma levels of epinephrine, norepinephrine, and estradiol had been measured and echocardiograms had been obtained within 48 hours of SAH onset. Results-Twenty-four patients (31%) were found to sustain WMA on admission. Multivariate regression analysis revealed that decreased estradiol (P=0.018; OR, 0.902) and elevated norepinephrine levels (P=0.027; OR, 1.002) were associated with WMA. After quadrichotomization of 77 patients based on sex/WMA, plasma norepinephrine levels were markedly elevated in men with WMA, whereas estradiol levels were markedly decreased in women with WMA. Plasma norepinephrine and estradiol levels were not correlated. Fifty-four female patients with SAH were further quadrichotomized based on norepinephrine/estradiol levels with a threshold value of 1375 pg/mL for norepinephrine and 11 pg/mL for estradiol. The incidence of WMA in the high-norepinephrine/low-estradiol group was significantly higher than the low-norepinephrine/high-estradiol group. Conclusions-To our knowledge, this is the first study to evaluate the interrelation among catecholamine, estrogen, and SAH-induced WMA. Lack of estradiol in postmenopausal women may predispose them to develop WMA after poor-grade SAH. However, the precise role of multiple sex hormones in SAH-induced WMA should be evaluated in future prospective studies. (Stroke. 2012;43:1897-1903.)

Interventional neuroradiological treatments were practiced for the first time in 1974 when Sebinenko blocked the blood flow of a cerebral artery using a balloon catheter. This method was then expanded to aneurysm treatment but was not adopted worldwide until sufficient tools were developed for that purpose. The use of digital subtraction angiography (DSA) spread quickly worldwide after that the first stable aneurysm embolization was presented in 1991 by Guglielmi et al. The embolization was achieved by using electricity for delivering a coil inside the aneurysm. Generalized use of 3D DSA is the consequence of the remarkable improvements in accuracy done in recent years. Such technology increased safety during endovascular treatments. Therefore, interventional radiology used is not only for cerebral aneurysm treatments but also for various endovascular tools research and development, such as the creation of new treatment techniques for stenosis in carotid arteries, acute strokes and cerebral arteriovenous malformation. In this chapter, we will explain conventional and endovascular treatments for cerebrovascular diseases such as cerebral aneurysms, carotid artery stenosis, acute stroke and cerebral hemorrhage. Additionally, we will present how recently, from other minimally invasive treatments, the use of endoscopes has been adopted for neurosurgery. © 2012 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

Development of adjacent segment degeneration following anterior cervical decompression and fusion (ACDF) is still controversial, as adjacent-level kinematics is poorly understood. This study reports preliminary data from a high-accuracy 3D analysis technique developed for in vivo cervical kinematics. From nine cervical spondylosis patients, four underwent single-level ACDF, and five underwent two-level ACDF using cylindrical titanium cage implant(s). Pre- and post-surgical CT scans were taken in flexion, neutral and extended positions, allowing us to compute segmental ranges of motion for rotation and translation, and 3D disc-height distributions. Differences in segmental motions and disc-height between fused and adjacent levels were analyzed with a Wilcoxon signed-rank test. Results are presented as mean +/- A SEM. The flexion/extension angular-ROM at the fusion level decreased after surgery (7.46 +/- A 1.17A degrees vs. 3.14 +/- A 0.56A degrees, p < 0.003). The flexion/extension angular-ROM at one caudal adjacent level to the fusion level (3.97 +/- A 1.29A degrees) tended to be greater post-operatively (6.11 +/- A 1.44A degrees, p = 0.074). Translation in the anterior-posterior direction during flexion/extension at the fusion level decreased after surgery (1.22 +/- A 0.20 mm vs. 0.32 +/- A 0.11 mm, p < 0.01). No differences were found in adjacent-level disc heights between both study time-points. This study showed increased segmental motion in flexion/extension angular-ROM at one level adjacent to ACDF. However, increases in the rotational angular-ROM were not statistically significant when cranial/caudal adjacent levels were analyzed separately. This preliminary study highlighted the capabilities of a 3D-kinematic analysis method to detect subtle changes in kinematics and disc height at the adjacent levels to ACDF. Thus, reliable evidence related to ACDF's influence on adjacent-level cervical kinematics can be collected.

DNAメチル化剤テモソロミド(TMZ)の導入は,悪性グリオーマの薬物治療のうえで大きな発展をもたらし,従来その効果が明確な形で証明されていなかった化学療法が,生存期間の延長という治療成績の向上を示したということは非常に有意義である.しかし,そのー方で,悪性グリオーマは今なお根治のほぼ不可能な疾患であり,最近の脳神経外科関連の他分野にみられる進歩と比べると,いまだに多くの課題が残っている.これらを解決するために悪性グリオーマの生物学についての研究が精力的に行われ,遺伝学的解析による予後予測や治療感受性予測の流れができている.中でも0^6-methylguanine-DNA methyltransferase (MGMT)のプロモーター領域メチル化とTMZによる膠芽腫の治療成績の関係は近年注目され,そこからMGMTの不活化によるTMZの治療効果増強の試みがなされた.これはMGMT阻害剤の併用や,TMZの投与量・スケジュールの変更によって行われたが,必ずしも好結果を示さす,TMZ耐性がMGMTのみで説明されるわけではないこととともに,DNA攻撃型の化学療法剤による悪性グリオーマ治療の限界も示唆される.そこで,グリオーマの生物学的特性を利用した分子標的治療が期待され,欧米ではすでに数種類の薬物が臨床試験の対象となった.本稿では悪性グリオーマの臨床研究から得られた知見を紹介しながら,腫瘍生物学との関連について説明し,今後の治療発展のための問題点を提起する.

Although both the alkylating agent temozolomide (TMZ) and oncolytic viruses hold promise for treating glioblastoma, which remains uniformly lethal, the effectiveness of combining the two treatments and the mechanism of their interaction on cancer stem cells are unknown. We investigated the efficacy of combining TMZ and the oncolytic herpes simplex virus (oHSV) G47 delta in killing glioblastoma stem cells (GSCs), using Chou-Talalay combination index analysis, immunocytochemistry and fluorescence microscopy, and neutral comet assay. The role of treatment-induced DNA double-strand breaks, activation of DNA damage responses, and virus replication in the cytotoxic interaction between G47 delta and TMZ was examined with a panel of pharmacological inhibitors and short-hairpin RNA (shRNA)-mediated knockdown of DNA repair pathways. Comparisons of cell survival and virus replication were performed using a two-sided t test (unpaired). The survival of athymic mice (n = 6-8 mice per group) bearing GSC-derived glioblastoma tumors treated with the combination of G47 delta and TMZ was analyzed by the Kaplan-Meier method and evaluated with a two-sided log-rank test. The combination of G47 delta and TMZ acted synergistically in killing GSCs but not neurons, with associated robust induction of DNA damage. Pharmacological and shRNA-mediated knockdown studies suggested that activated ataxia telangiectasia mutated (ATM) is a crucial mediator of synergy. Activated ATM relocalized to HSV DNA replication compartments where it likely enhanced oHSV replication and could not participate in repairing TMZ-induced DNA damage. Sensitivity to TMZ and synergy with G47 delta decreased with O(6)-methylguanine-DNA-methyltransferase (MGMT) expression and MSH6 knockdown. Combined G47 delta and TMZ treatment extended survival of mice bearing GSC-derived intracranial tumors, achieving long-term remission in four of eight mice (median survival = 228 days; G47 delta alone vs G47 delta + TMZ, hazard ratio of survival = 7.1, 95% confidence interval = 1.9 to 26.1, P = .003) at TMZ doses attainable in patients. The combination of G47 delta and TMZ acts synergistically in killing GSCs through oHSV-mediated manipulation of DNA damage responses. This strategy is highly efficacious in representative preclinical models and warrants clinical translation.

Objective: To discuss the role of FLOW 800 innovative software for analytical color visualization and objective evaluation of fluorescence videos obtained by microscope-integrated intraoperative indocyanine green (ICG) fluorescence angiography in arteriovenous malformations (AVM) surgery. Materials and Methods: Microscope-integrated intraoperative FLOW 800 was used and evaluated in three consecutive AVM surgeries over a period of two months. The role of FLOW 800 to distinguish feeding arteries from arterialized veins and other arteries was evaluated. Its advantages and limitations over conventional intraoperative ICG angiography were evaluated. Results: This software was found to be useful in identifying arterial feeders, arterialized veins and other arteries in all the three patients and it gives additional information on the status of AVM before and after clipping suspected feeders which is sometimes difficult to interpret on conventional ICG angiography. Conclusion: Flow 800 is a reliable and useful addition to microscope-integrated color ICG video angiography. Although its role is limited in deep-seated AVMs, if properly dissected and exposed it can give useful information which can be easily interpretable and reproducible.

Temozolomide constitutes current standard of care for adult patients with high-grade gliomas. However, results for pediatric gliomas are rather disappointing. In order to investigate the molecular differences between pediatric and adult gliomas that could affect sensitivity to temozolomide, we studied 23 pediatric non-ependymal, non-pilocytic gliomas in comparison to 59 consecutive adult gliomas for the expression of O(6)-methylguanine methyltransferase (MGMT) and the DNA mismatch repair protein, mutS homolog 6 (MSH6) by immunohistochemistry, as well as for the presence or absence of promoter methylation of the MGMT gene by methylation-specific PCR. The expression of MGMT in pediatric gliomas was significantly higher than in adult gliomas, as shown by immunohistochemistry (p=0.00004). This association was conserved if statistical analysis was carried out only in astrocytic tumors (diffuse astrocytoma, anaplastic astrocytoma and glioblastoma, p=0.00007), or in oligodendroglial tumors (oligodendroglioma and anaplastic oligodendroglioma, p=0.020). Although methylation-specific PCR was successfully performed only in 15 pediatric gliomas, it also showed a trend toward less frequent methylation in pediatric as opposed to adult gliomas (p=0.242). MSH6 was almost equally expressed in pediatric and adult gliomas. Pediatric gliomas appear to have a distinct molecular profile associated with resistance to temozolomide. Higher expression of MGMT and a trend toward less frequent methylation of the promoter region of MGMT gene may partly account for relative resistance to temozolomide in pediatric gliomas as compared to adult gliomas.

BACKGROUND: In ruptured cerebral aneurysms (RCAs), identification of the rupture point of a cerebral aneurysm is useful for treatment planning. In unruptured cerebral aneurysms (URCAs), detection of the risk of aneurysmal rupture is also useful for patient management. OBJECTIVE: Electrocardiographic (ECG)-gated 3D-CT angiography was performed for patients with RCAs and URCAs using 320-row area detector CT (ADCT) to detect pulsation of the cerebral aneurysms. The clinical usefulness of this method was then evaluated. METHODS: Twelve patients had 12 RCAs, and 39 patients had 53 URCAs. A 320-row ADCT system was used to scan. ECG-gated reconstruction was then performed with the R-R interval divided into 20 phases. RESULTS: Pulsation was observed in 10 of the 12 RCAs. The bleeding site was considered to correspond to the area of pulsation. Pulsation was observed in 14 of 53 URCAs. Thirteen patients with 18 URCAs were followed. Of the 11 URCAs in which pulsation was not observed, 1 showed a change in shape. Of the 7 URCAs in which pulsation was observed, 3 showed a change in shape. URCAs in which pulsation was observed were more likely to show a change in shape (P = .082). CONCLUSION: The area of pulsation was found to correspond to the bleeding site in many RCAs. This information would be extremely useful for treatment planning. The detection of pulsation in an URCA is therefore considered to provide useful information for patient management.

We present our preliminary experience with intraoperative near-infrared indocyanine green-videoangiography (ICG-VA) and analysis of blood flow dynamics using fluorescence intensity assessment in cerebral aneurysm clipping surgery. Thirty-nine patients with 43 intracranial aneurysms underwent microsurgical clipping. Intraoperative ICG-VA was performed before and after clip application. An infrared fluorescence module integrated into a surgical microscope was used to visualize fluorescence in the surgical field and we recorded the emitted fluorescent light. An integrated analytical visualization tool simultaneously analyzed the video sequence and converted it into an intensity diagram, which allowed an objective evaluation of the results rather than the subjective assessment of fluorescence using ICG-VA. Overall, ICG-VA was performed 137 times. Incomplete clipping was detected in four patients, which allowed suitable adjustment to completely obliterate the aneurysm. In 12 patients, perforators arising close to, or from, the aneurysmal neck were identified in the surgical field. In three patients, the ICG-VA intensity diagram provided valuable information leading to modification of the primary surgical maneuver. ICG-VA provides high resolution images allowing real-time assessment of the blood flow in the parent artery and arterial branches, including the perforators. The intensity diagram is useful for providing a more objective record of the hemodynamics than the traditional ICG-VA, which relies more on subjective assessment and may allow interobserver variability. We conclude that ICG-VA, combined with the intensity diagram, can reduce the morbidity and complications associated with aneurysm clipping and improve patient outcomes. (C) 2011 Elsevier Ltd. All rights reserved.

BACKGROUND: Gliomas are classified into pathologically defined subgroups. However, the tumors in the same entity could show varied 'clinical courses. Recently, various studies revealed that genetic analyses of gliomas can provide clinically relevant information. OBJECTIVE: To investigate the correlation between genetic characterization and clinical information of adult supratentorial grade II-III gliomas to establish a genetic classification of these tumors. METHODS: We analyzed the genetic profile of tumor samples microdissected from formalin-fixed archival tissue sections based on the defined selection criteria of tumor region using a comparative genomic hybridization method. We collected genetic and clinical data from 140 adult supratentorial gliomas of World Health Organization grade II-III and classified the tumors analyzed into subgroups according to chromosomal copy number aberrations. The relationship between histologic or genetic subclassification and clinical features was analyzed. RESULTS: The tumors were classified into subgroups based on the genetic profiles. Tumors with +7q and those with -1p/19q showed long progression-free survival, and loss of 10q in association with gain of 7p (+7/-10q) appeared to predict poor outcome. Most tumors with histologic diagnosis of glioblastoma showed +7/-10q; however, World Health Organization grade II-III gliomas contained a variety of genetic subgroups that correlated well with the clinical course, and this might explain why these tumors do not respond uniformly to therapies. CONCLUSION: Our pilot study suggests that care must be taken in clinical studies of these tumors because, unlike glioblastoma, grade II-III tumors may contain genetically distinct subgroups with different sensitivity to the therapies.