-
[show abstract]
[hide abstract]
ABSTRACT: We treated a case of recurrent glioblastoma (GBM) with bevacizumab and assessed its effect biologically. A 55-year-old man with a left frontal lobe GBM was experiencing recurrence 7 months postoperation. We administered bevacizumab concomitant with temozolomide (TMZ). Follow-up magnetic resonance imaging (MRI) showed dramatic but temporal tumor reduction; however, the patient died of re-recurrent disease 6 months after beginning bevacizumab. We obtained an autopsy and analyzed the detailed molecular change. In the autopsy specimen, the quantity of microvessels was significantly reduced. Vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 were downregulated, most likely due to a negative feedback mechanism by blocking of VEGF signaling. Matrix metalloproteinase (MMP)-2 and membrane-type 1 MMP were upregulated, resulting in the higher activation of MMP-2 in the autopsy specimen. MIB-1 staining index and phosphorylation levels of p44/42-mitogen-activated protein kinase did not change, whereas phosphorylated protein kinase B (Akt) was decreased in the autopsy specimen, suggesting compensation and/or amplification of other proliferative signaling pathways such as suppression of apoptosis signaling. Consequently, bevacizumab might inhibit the VEGF autocrine loop, which then causes a change in molecular expression related not only to enhancement of tumor invasion but also maintenance of tumor proliferation.
Brain Tumor Pathology 03/2013; · 1.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUNDE: The concept of human brain reorganization due to slow-growing lesions, including low-grade glioma, has been gradually and generally accepted. However, few cases have been reported in which the reorganization, especially in the topographic pure primary motor cortex, was observed during brain surgery. We report a case of slow-growing oligodendroglioma located in the pure primary motor cortex, as detected by magnetic resonance imaging that could be resected in part thanks to the brain plasticity. Moreover, we describe a pitfall of topographic guidance using somatosensory-evoked potential (SEP) monitoring. CASE DESCRIPTION: A 36-year-old right-handed patient underwent resection of a gradually growing oligodendroglioma located in the right primary motor cortex, with no other adjacent lesions, 8 years after the initial biopsy. The central sulcus was defined with intraoperative SEP monitoring in both operations. Based on the findings of the intraoperative direct electrical stimulation (DES) under awake craniotomy, we suspect that motor function shifted posteriorly and reorganized beyond the central sulcus. CONCLUSION: Pure primary motor cortex could be reorganized by its own lesion. In reorganized brain, topographic central sulcus defined based on SEP findings may be an inappropriate guidance to estimate true functional area. In such a condition, intraoperative DES under awake craniotomy makes it feasible to resect pure primary motor cortex invaded by tumors.
World Neurosurgery 01/2013; · 0.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an "on" or "off" switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.
Advances in experimental medicine and biology 01/2013; 986:143-70. · 1.09 Impact Factor
-
Rihua Jin,
Mitsutoshi Nakada,
Lei Teng,
Takuya Furuta,
Hemragul Sabit,
Yutaka Hayashi,
Tim Demuth,
Atsushi Hirao,
Hiroshi Sato,
Gang Zhao, Jun-Ichiro Hamada
[show abstract]
[hide abstract]
ABSTRACT: Molecular targeted therapy can potentially provide more effective treatment for patients with high-grade gliomas. Notch and Akt are notable target molecules as they play important roles in a variety of cellular processes, such as regeneration, differentiation, proliferation, migration, and invasion. Here, we assessed the therapeutic possibility of inhibiting Notch and Akt in gliomas using the clinically available, selective small molecule inhibitors MRK003 and MK-2206. We evaluated their efficacy individually and as a combination therapy in U251 and U87 glioma cell lines. We confirmed that MK-2206 effectively inhibits Akt phosphorylation in a dose-dependent manner, whereas MRK003 inhibits Notch signaling and Akt phosphorylation. Both MRK003 and MK-2206 significantly inhibited cell growth, migration, and invasion in a dose-dependent manner. Akt dephosphorylation was enhanced by combination therapy with MRK003 and MK-2206. However, the effect of combination treatment did not exceed that of MK-2206 monotherapy in proliferation assay. Inhibition of invasion, further enhanced by combination therapy, correlated with increased Akt inactivation. In summary, combination therapy with MRK003 and MK-2206 may be effective for inhibiting invasion but not proliferation.
Neuroscience Letters 12/2012; · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Awake surgery for lesions in the non-dominant parietal lobe is rare. We report two cases of right parietal lobe glioma for which awake surgery was performed in order to avoid ataxie optique and hemispatial neglect due to injury in the superior and inferior parietal lobule, respectively. Among several tests to assess the dysfunction of spatial recognition, line bisection test was selected for the task during awake surgery because of its simplicity, easy repetition, and utility. The tumor was successfully removed without any neurological deficit in both the cases. The line bisection test is simple and useful for preserving spatial recognition during an awake surgery.
No shinkei geka. Neurological surgery 12/2012; 40(12):1087-93. · 0.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 63-year-old woman presented with dizziness followed by gait disturbance and loss of appetite. Magnetic resonance image (MRI) showed that a lesion located in the medulla oblongata, appearing as hyperintense on T2-weighted image and with slight enhancement area, appeared in the ventral aspect of the mass on T1-weighted MR imaging with gadolinium. It was diagnosed as high-grade brain-stem glioma and the patient underwent chemoradiotherapy. However, she died 18 days after treatment, and autopsy was performed. The pathological diagnosis was glioblastoma (GBM) with unmethylated O-6-methylguanine-DNA methyltransferase promoter and wild isocitrate dehydrogenase 1 gene. We report an extremely short clinical course of adult GBM in medulla oblongata with genetic analysis and present a review of the literature.
Brain Tumor Pathology 09/2012; · 1.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Object Disturbance of the arcuate fasciculus in the dominant hemisphere is thought to be associated with language-processing disorders, including conduction aphasia. Although the arcuate fasciculus can be visualized in vivo with diffusion tensor imaging (DTI) tractography, its involvement in functional processes associated with language has not been shown dynamically using DTI tractography. In the present study, to clarify the participation of the arcuate fasciculus in language functions, postoperative changes in the arcuate fasciculus detected by DTI tractography were evaluated chronologically in relation to postoperative changes in language function after brain tumor surgery. Methods Preoperative and postoperative arcuate fasciculus area and language function were examined in 7 right-handed patients with a brain tumor in the left hemisphere located in proximity to part of the arcuate fasciculus. The arcuate fasciculus was depicted, and its area was calculated using DTI tractography. Language functions were measured using the Western Aphasia Battery (WAB). Results After tumor resection, visualization of the arcuate fasciculus was increased in 5 of the 7 patients, and the total WAB score improved in 6 of the 7 patients. The relative ratio of postoperative visualized area of the arcuate fasciculus to preoperative visualized area of the arcuate fasciculus was increased in association with an improvement in postoperative language function (p = 0.0039). Conclusions The role of the left arcuate fasciculus in language functions can be evaluated chronologically in vivo by DTI tractography after brain tumor surgery. Because increased postoperative visualization of the fasciculus was significantly associated with postoperative improvement in language functions, the arcuate fasciculus may play an important role in language function, as previously thought. In addition, postoperative changes in the arcuate fasciculus detected by DTI tractography could represent a predicting factor for postoperative language-dependent functional outcomes in patients with brain tumor.
Journal of Neurosurgery 08/2012; · 2.96 Impact Factor
-
Clinical neurology and neurosurgery 07/2012; · 1.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pituitary apoplexy during pregnancy is so rare that only 15 cases (12 pituitary adenomas, 2 lymphocytic neurohypophysitis, and 1 normal pituitary gland) have been published to date. Here, we report the case of a pregnant woman presenting with pituitary apoplexy from a nonfunctioning pituitary adenoma and provide a possible mechanism and management option for postoperative diabetes insipidus (DI).
A 26-year-old woman presented with sudden onset of headache and bitemporal hemianopsia in the 26th week of her first pregnancy. Magnetic resonance imaging clearly revealed an 18 mm pituitary mass with a fluid-fluid level component displacing the optic chiasma upward. Endonasal endoscopic transsphenoidal surgery was successfully carried out 7 days after the onset of symptoms. DI became apparent immediately after the operation and was not controllable by arginine vasopressin (AVP) but by 1-desamino-8-D-arginine vasopressin (DDAVP) instead. This finding suggests an association between DI and vasopressinase secretion from the placenta, because vasopressinase can degrade AVP but not DDAVP. DI had diminished by the time the patient delivered a healthy girl at the 40th week of gestation.
Postoperative DI associated with pituitary apoplexy during pregnancy should be treated by DDAVP, which is not affected by placental vasopressinase secretion.
Neuro endocrinology letters 04/2012; 33(2):107-12. · 1.30 Impact Factor
-
Clinical neurology and neurosurgery 02/2012; 114(7):1049-51. · 1.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: High-grade (World Health Organization grades II and III) meningiomas grow aggressively and recur frequently, resulting in a poor prognosis. Assessment of tumor malignancy before treatment initiation is important. We attempted to determine predictive factors for high-grade meningioma on magnetic resonance (MR) imaging before surgery. We reviewed 65 meningiomas (39 cases, benign; 26 cases, high-grade) and assessed four factors: (1) tumor-brain interface (TBI) on T1-weighted imaging (T1WI), (2) capsular enhancement (CapE), i.e., the layer of the tumor-brain interface on gadolinium-enhanced T1WI (T1Gd), (3) heterogeneity on T1Gd, and (4) tumoral margin on T1Gd. All four factors were useful in distinguishing high-grade from benign meningiomas, according to univariate analysis. On multivariate regression analysis, unclear TBI and heterogeneous enhancement were independent predictive factors for high-grade meningioma. In meningiomas with an unclear TBI and heterogeneous enhancement, the probability of high-grade meningioma was 98%. Our data suggest that this combination of factors obtained from conventional sequences on MR imaging may be useful to predict high-grade meningioma.
Journal of Neuro-Oncology 02/2012; 108(1):147-52. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Because extra-axial cavernous malformations (CMs) are rare, the common clinical course remains unclear. We report the case of a patient with progressive CM originating from the cerebellar tentorium.
A 64-year-old woman was admitted to our hospital with the complaint of diplopia. Magnetic resonance (MR) imaging revealed a lesion attached to the left cerebellar tentorium, close to the cerebral peduncle. This well-demarcated lesion rapidly enlarged for 3 months and eroded into the midbrain. Cerebral angiography showed a branch of the middle meningeal artery supplying the lesion and pooling of the contrast medium in the venous phase. A dark reddish and mulberry-like mass of the tentorium was observed intraoperatively, allowing the diagnosis of a tentorial CM. The feeding artery was identified in the tentorium and was coagulated. Postoperative MR imaging showed remarkable mass reduction and central necrosis of the lesion. However, the lesion recurred in 3 months; consequently, gamma knife radiosurgery was performed. After an additional 2 months, the lesion shrank in response to the radiosurgery.
We report an extremely rare case of tentorial CM which showed rapid growth in a short period. Coagulation of the feeding artery was not sufficient to control the lesion. Gamma knife radiosurgery may prove highly effective for recurrent lesions.
Surgical neurology international. 01/2012; 3:18.
-
[show abstract]
[hide abstract]
ABSTRACT: Schwannomas of the orbit are very rare benign neoplasms. Intraorbital cystic schwannomas originating from the frontal nerve are even rarer, with only 1 case reported to date. This is most likely due to the fact that, in most cases, the origin of the orbital schwannoma cannot be identified intraoperatively. The nerve origin is usually speculated from histological examination of the specimen and the postoperative neurological deficits of the patient. Here, we present the case of a 65-year-old woman with a one-month history of exophthalmos, whose orbital cystic lesion was completely removed by microsurgical transcranial operation. Intraoperatively, the continuity between the tumor and frontal nerve was seen macroscopically, leading us to confirm the frontal nerve as an origin of the tumor, which was consistent with the postoperative neurological findings. The diagnosis of the tumor was established as schwannoma from the histological examination. As a differential diagnosis of the orbital cystic lesions, the possibility of schwannomas should be kept in mind.
Case reports in ophthalmological medicine. 01/2012; 2012:604574.
-
[show abstract]
[hide abstract]
ABSTRACT: We developed a new 6-Fr guiding catheter (Slim Guide(®)) that features a large lumen (0.072 inch) for performing advanced techniques as are required in patients with wide-necked aneurysms whose treatment with a single microcatheter is difficult.
The Slim Guide was used to address 30 saccular and 20 dissecting aneurysms. All 50 patients presented with subarachnoid hemorrhage. To perform the advanced techniques we used SL-10(®) or Excel 14(®) and Hyperform(®) balloon microcatheters.
Of the 30 patients with saccular aneurysms, 20 were treated with the double microcatheter- and the other 10 with the balloon assist technique. All 20 patients with dissecting aneurysms were treated with the double microcatheter technique. We encountered slight interference during the treatment of one saccular aneurysm with the balloon assist technique using the Slim Guide guiding catheter; another patient with a saccular aneurysm treated with the balloon assist technique suffered a minor transient ischemic complication.
With the Slim Guide, the risks inherent in the application of advanced techniques may be decreased. Its use facilitates the coil embolization of aneurysms that pose treatment challenges.
Surgical neurology international. 01/2012; 3:59.
-
[show abstract]
[hide abstract]
ABSTRACT: A combined therapy of the alkylating agent temozolomide (TMZ) and radiotherapy is standard treatment, and it improves the survival of patients with newly diagnosed glioblastoma (GBM). The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) removes the most cytotoxic lesions generated by TMZ, O(6)-methylguanine, establishing MGMT as one of the most important DNA repair mechanisms of TMZ-induced DNA damage. Thus, the expression of MGMT, its activity, and its promoter methylation status are associated with the response of GBM to TMZ, confirming that MGMT promotes clinical resistance to TMZ. Previous studies have shown that a variety of drugs such as interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increased the sensitivity of TMZ through MGMT-dependent or MGMT-independent mechanisms. In this review, we describe drugs and promising molecules that influence the responsiveness of GBM to TMZ and discuss their putative mechanism of action. In MGMT-positive GBMs, drugs that modulate MGMT activity could enhance the therapeutic activity of TMZ. Thus, administration of these drugs as an adjunct to TMZ chemotherapy may have clinical applications in patients with malignant gliomas to improve the outcome.
Frontiers in oncology. 01/2012; 2:98.
-
[show abstract]
[hide abstract]
ABSTRACT: A 60-year-old man was admitted to our hospital with sudden onset of motor aphasia, Gerstmann syndrome, and incomplete right hemiparesis one week after administration of chemotherapy for mucosa-associated lymphoid tissue (MALT) lymphoma. Computed tomography showed an intracerebral hematoma in the left subcortical area. Cerebral angiography revealed 2 aneurysms on the distal middle cerebral artery (MCA) that increased in size in the course of 2 weeks. The aneurysms were excised and a bypass placed using a superficial temporal artery (STA) graft. Histological study showed no bacteria, infiltration of inflammatory cells, or lymphoma cells in the aneurysm wall. The chemotherapy against MALT lymphoma was highly effective, so we presumed that the lymphoma cells had disappeared. The source of the distal MCA aneurysms was thought to be oncotic. Distal MCA aneurysms caused by MALT lymphoma are extremely rare. Surgical reconstruction using the STA may be effective in patients with ruptured distal MCA aneurysms if the wall is intact.
Neurologia medico-chirurgica 01/2012; 52(6):443-5. · 0.61 Impact Factor
-
Tomoya Kamide,
Yasuko Kitao,
Toshiaki Takeichi,
Akiko Okada,
Hiromi Mohri,
Ann Marie Schmidt,
Takayuki Kawano,
Seiichi Munesue,
Yasuhiko Yamamoto,
Hiroshi Yamamoto, Jun-ichiro Hamada,
Osamu Hori
[show abstract]
[hide abstract]
ABSTRACT: The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in a diverse range of pathological conditions. To analyze the roles of RAGE and its decoy receptor, endogenous secretory RAGE (esRAGE), in the global cerebral ischemia, three different mouse cohorts, wild-type, RAGE⁻/⁻, and esRAGE transgenic (Tg) mice were subjected to bilateral common carotid artery occlusion (BCCAO). RT-PCR and immunohistochemical analysis revealed that expression of RAGE was induced in the vascular cells at 12 h, and then in the neurons and glia from 3 to 7 days in the hippocampus after BCCAO. The numbers of surviving neurons in the hippocampal CA1 region were significantly higher in RAGE⁻/⁻ and esRAGE Tg mice than those in wild-type mice in the periods between 24 h and 7 days after BCCAO. Lower levels of 3-nitrotyrosine (3-NT) and higher levels of endothelial nitric oxide synthase (eNOS), together with enlarged vascular areas were observed in RAGE⁻/⁻ and esRAGE Tg mice at 12 h after BCCAO. In the later periods, expressions of glia-derived inflammatory mediators TNFα and inducible nitric oxide synthase (iNOS) were reduced in RAGE⁻/⁻ and esRAGE Tg mice. These results suggest that RAGE may contribute to delayed neuronal death after global cerebral ischemia by enhancing vascular injury and deleterious glia-mediated inflammation.
Neurochemistry International 12/2011; 60(3):220-8. · 2.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: At present, the risk of future hemorrhage or ischemic insult from vertebral artery (VA) dissection cannot be estimated from available imaging data. We investigated the relationship between symptoms and the angiographic patterns of the dissecting site on balloon test occlusion (BTO) to develop guidelines for clinical decision-making.
We retrospectively reviewed 18 patients with unilateral VA dissection who presented with subarachnoid hemorrhage (SAH) or cerebral infarction. We analyzed the angiographic findings at the dissecting site on contralateral VA angiograms during BTO of the affected VA, classified the angiographic patterns into two types, and compared the symptoms they presented.
Patients with dissection opacified from the distal to the proximal side are more likely to present with cerebral infarction than SAH. Conversely, patients with dissection opacified from the proximal to the distal side had a significantly higher incidence of SAH.
Angiographic findings at the dissecting site on contralateral VA angiograms during BTO of the affected VA are helpful for considering the treatment and prognosis of patients with VA dissecting aneurysms.
Neuroradiology 12/2011; 54(8):857-62. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recently, intraoperative mapping has disclosed that, in addition to the classic language centers (that is, the Broca and Wernicke centers), other cortical regions may also play an important role in language organization. In the prefrontal cortex, although the lateral superior frontal gyrus (LSFG) could have language-related functions, there are no detailed reports that demonstrate the anatomical connection between the LSFG and other well-known language cortices, such as the Broca center. To show the existence of the structural connection, white matter association fibers between the inferior frontal gyrus (IFG) and the LSFG were examined using fiber dissection (FD) and diffusion tensor (DT) imaging-based tractography.
Eight cadaveric cerebral hemispheres were dissected to reveal the association fibers between the IFG and LSFG. The DT imaging-based tractography studies targeting the prefrontal cortex were obtained in 53 right-handed patients who had no organic cerebral lesions.
The association fiber tract between Brodmann area 44/45 (the Broca center in the dominant hemisphere) and LSFG were detected in all specimens by FD. In the DT imaging-based tractography studies, the tract was identified in all patients bilaterally, except for the 4 in whom the tract was detected only in the left hemisphere. This tract was spread significantly wider in the left than in the right hemisphere, and left lateralization was evident in male patients.
Based on its character, this tract was named the Broca-LSFG pathway. These findings suggest a close relationship between this pathway and language organization. The structural anatomy of the Broca-LSFG pathway may explain speech disturbances induced by LSFG stimulation that are sometimes observed during intraoperative language mapping.
Journal of Neurosurgery 11/2011; 116(2):323-30. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The anterolateral approach is one of the main routes for accessing suprachiasmatic lesions involving the anterior communicating artery (AComA) complex. Pterional (PT) craniotomy and its alternatives, including orbitozygomatic, orbitopterional, and mini-supraorbital craniotomies, have been developed as tailored frontotemporal craniotomies. One of the main differences between PT craniotomy and its alternatives is the removal of the orbital bone along with the sphenoid wing. However, which bone part is the most important to remove has not been discussed in relation to frontal lobe retraction. We have evaluated how the removal of the supraorbital bar versus the removal of the lateral orbital wall along with the sphenoid wing affects the relationship between the levels of frontal lobe retraction and area of exposure (AOE) in the suprachiasmatic region.
We performed three types of craniotomies: PT craniotomy, PT craniotomy with the removal of the supraorbital bar (PT-SO craniotomy), and PT craniotomy with the removal of the lateral orbital wall along with the sphenoid wing, i.e., the frontal process of the zygomatic bone and the orbital and cerebral faces of the greater sphenoid wing (PT-LO-SW craniotomy). For each craniotomy, the AOE around the suprachiasmatic region was measured at four different levels of frontal lobe retraction, namely, 5, 10, 15, and 20 mm, from the cranial base.
At 5-mm retraction, PT-LO-SW craniotomy was the only craniotomy in which the AComA complex was visible. At 10-mm retraction, PT-LO-SW craniotomy afforded the greatest AOE among the three craniotomies, and the AOE was significantly greater than that of PT craniotomy (P = 0.025). At 15- and 20-mm retraction, there were no significant differences among the three craniotomies.
Treatment of lesions in the suprachiasmatic region via an anterolateral route involving a frontotemporal craniotomy requires sufficient removal of the lateral orbital wall along with the greater sphenoid wing so that brain retraction is minimized.
World Neurosurgery 11/2011; 77(2):342-8. · 0.68 Impact Factor
