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Shinji Yamamoto, Toshiya Momose, Masaru Aoyagi and Kikuo Ohno

✓ Expansion of intracerebral hematoma usually occurs in the chronic phase because of repeated bleeding from preexisting vascular anomalies or exudation of blood from capillaries of the capsule. In contrast, spontaneous intracerebral hematoma expanding during the acute phase of hemorrhage without rebleeding is seldom seen. Three such cases are reported, along with magnetic resonance (MR) and computerized tomography (CT) follow-up studies. The follow-up MR images and CT scans demonstrated no evidence of rebleeding, but revealed gradual expansion of a fluid component of the hematoma, beginning in the acute phase. Volume alterations posthemorrhage are carefully documented. There was a characteristic phenomenon of layering, with the red blood cell component of the clot settling by gravity and the serum separating as well as seen in a test tube, depending on whether a preservative was used. Examination of blood samples indicated a possible correlation between expansion of the hematoma and the activities of both the fibrinolytic system and coagulation factors.

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Maki Mukawa, Tadashi Nariai, Yoshiharu Matsushima and Kikuo Ohno

Object

The authors compared the clinical features between familial and sporadic cases of moyamoya disease (MMD) by retrospectively analyzing data on patients with MMD registered in the database of Tokyo Medical and Dental University over a period of 28 years.

Methods

In total, 383 patients with hospital records at Tokyo Medical and Dental University from 1980 to 2007 were registered into the database. The data on all of these patients were retrospectively reviewed to clarify the occurrence of familial cases. Clinical features of child or adolescent patients (< 20 years of age) with MMD were compared between familial and sporadic cases in a subgroup of patients who were registered after 1995, initially diagnosed using MR angiography, and assessed using an intelligence scale.

Results

Familial occurrence was observed in 59 patients (15.4%) in 40 pedigrees. The clinical features of juvenile patients were analyzed in 124 patients, 22 (17.7%) of whom had familial histories. In comparison with the sporadic cases, patients with familial histories were significantly younger at onset (4.7 vs 6.6 years old), had significantly more cortical infarction (59.1% vs 25.5%), and had significantly more stenoocclusive lesions in the posterior cerebral artery (45.4% vs 24.5%). The rate of patients with intellectual disturbance (intelligence quotient < 75) was significantly larger in the familial cases (47.4%) than in the sporadic cases (17.8%).

Conclusions

This survey of the clinical features of familial MMD suggests that patients with familial MMD had a more serious clinical course in childhood than the sporadic MMD cases.

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Kaoru Tamura, Masaru Aoyagi, Noboru Ando, Takahiro Ogishima, Hiroaki Wakimoto, Masaaki Yamamoto and Kikuo Ohno

Object

Recent evidence suggests that a glioma stem cell subpopulation may determine the biological behavior of tumors, including resistance to therapy. To investigate this hypothesis, the authors examined varying grades of gliomas for stem cell marker expressions and histopathological changes between primary and recurrent tumors.

Methods

Tumor samples were collected during surgery from 70 patients with varying grades of gliomas (Grade II in 12 patients, Grade III in 16, and Grade IV in 42) prior to any adjuvant treatment. The samples were subjected to immunohistochemistry for MIB-1, factor VIII, GFAP, and stem cell markers (CD133 and nestin). Histopathological changes were compared between primary and recurrent tumors in 31 patients after radiation treatment and chemotherapy, including high-dose irradiation with additional stereotactic radiosurgery.

Results

CD133 expression on glioma cells was confined to de novo glioblastomas but was not observed in lower-grade gliomas. In de novo glioblastomas, the mean percentage of CD133-positive glioma cells in sections obtained at recurrence was 12.2% ± 10.3%, which was significantly higher than that obtained at the primary surgery (1.08% ± 1.78%). CD133 and Ki 67 dual-positive glioma cells were significantly increased in recurrent de novo glioblastomas as compared with those in primary tumors (14.5% ± 6.67% vs 2.16% ± 2.60%, respectively). In contrast, secondary glioblastomas rarely expressed CD133 antigen even after malignant progression following radiotherapy and chemotherapy.

Conclusions

The authors' results indicate that CD133-positive glioma stem cells could survive, change to a proliferative cancer stem cell phenotype, and cause recurrence in cases with de novo glioblastomas after radiotherapy and chemotherapy.

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Toshihiko Kuroiwa, Naoyuki Miyasaka, Zhao Fengyo, Ichiro Yamada, Makoto Nakane, Tsukasa Nagaoka, Akira Tamura and Kikuo Ohno

✓Magnetic resonance (MR) imaging is a powerful tool for detecting and characterizing ischemic edema, a serious complication of ischemic cerebrovascular disorders. In this article the authors investigate the relationships between MR imaging findings and structural/ultrastructural changes in ischemic brain edema by using various animal models of experimental cerebral ischemia. The authors observed the following: 1) Ischemic edema was detectable by diffusion weighted MR imaging as early as 15 minutes after the onset of vascular occlusion. A decrease in the apparent diffusion coefficient (ADC) corresponded to the early cellular/cytotoxic type of brain edema and the decrease was proportionate to the degree of intracellular water accumulation. 2) Postischemic transient normalization of the ADC after the initial decrease did not signify histological recovery but rather slowly progressing infarction. 3) Histological degradation of postischemic tissue correlated with the decrease in tissue elasticity and the magnetization transfer ratio. 4) Transient cytotoxic edema localized in the substantia nigra preceding neuronal death was detectable on MR images after ipsilateral striatal infarction. Thus, MR imaging is a powerful tool for detecting and characterizing brain edema associated with ischemic stroke.

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Kaoru Tamura, Masaru Aoyagi, Hiroaki Wakimoto, Noboru Ando, Tadashi Nariai, Masaaki Yamamoto and Kikuo Ohno

Object

Recent evidence suggests that a glioma stem cell subpopulation might contribute to radioresistance in malignant gliomas. To investigate this hypothesis, the authors examined recurrent malignant gliomas for histopathological changes after high-dose irradiation with Gamma Knife surgery (GKS) and external beam radiation therapy (EBRT).

Methods

Thirty-two patients with malignant gliomas (Grade 3 in 8 patients, Grade 4 in 24) underwent GKS in combination with EBRT. Serial MR and L-[methyl-11C] methionine PET images were employed to assess remnant or recurrent tumors after GKS. Twelve patients underwent surgical removal after GKS and EBRT. Histological sections were subjected to immunohistochemistry for MIB-1, factor VIII, and stem cell markers, nestin and CD133.

Results

The site of GKS treatment failure was local in 16 (76.2%) of 21 patients with glioblastomas showing progression; in 9 of these 16 patients, the recurrence clearly arose within the target lesion of GKS. Histopathological examination after GKS and EBRT showed variable mixtures of viable tumor tissues and necrosis. Viable tumor tissues exhibited high MIB-1 indices but reduced numbers of tumor blood vessels. There was marked accumulation of CD133-positive glioma cells, particularly in remnant tumors within the necrotic areas, in sections obtained after GKS plus EBRT, whereas CD133-positive cells appeared very infrequently in primary sections prior to adjuvant treatment.

Conclusions

The results indicate that CD133-positive glioma stemlike cells can survive high-dose irradiation, leading to recurrence, despite prolonged damage to tumor blood vessels. This could be an essential factor limiting the effectiveness of GKS plus EBRT for malignant gliomas.

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Maki Mukawa, Tadashi Nariai, Motoki Inaji, Natsumi Tamada, Taketoshi Maehara, Yoshiharu Matsushima, Kikuo Ohno, Mariko Negi and Daisuke Kobayashi

The object of this study was to analyze the pathology of collateral vessels newly induced by indirect bypass surgery for moyamoya disease (MMD). An autopsy analysis was conducted on a 39-year-old woman with MMD who had died of a brainstem infarction. The patient had undergone bilateral indirect bypass surgeries 22 years earlier. Sufficient revascularization via bilateral external carotid arterial systems was confirmed by cerebral angiography before her death. Macroscopic observation of the operative areas revealed countless meandering vessels on the internal surface of the dura mater connected with small vessels on the brain surface and in the subpial brain tissue. Notably, microscopic analysis of these vessels revealed the characteristic 3-layer structure of an arterial wall. This autopsy analysis was the first to confirm that indirect bypass surgery had induced the formation of a new arterial network (arteriogenesis) and that this network had been maintained for more than 20 years to compensate for the chronic cerebral ischemia caused by the MMD.

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Maki Mukawa, Tadashi Nariai, Yoshiharu Matsushima, Yoji Tanaka, Motoki Inaji, Taketoshi Maehara, Masaru Aoyagi and Kikuo Ohno

Object

Surgical revascularization is considered an effective treatment for juvenile patients with moyamoya disease (MMD). Yet the long-term outcome in surgically treated patients still needs to be clarified. More than 30 years have passed since the authors' department started intensively treating pediatric patients with MMD using indirect anastomosis techniques. In this study the authors surveyed the current status of these patients.

Methods

Activities of daily living (ADLs) were surveyed and present clinical status was assessed based on the modified Rankin Scale (mRS). Cerebrovascular events subsequent to surgical treatment were also recorded.

Results

Since 1979, 208 patients younger than 19 years of age with MMD were surgically treated and followed up for > 3 years. Data were available on 172 patients (83%), who had been followed up for a mean of 14.3 years (range 3–32 years). Activity of daily living outcomes were as follows: 138 patients (80.2%) had mRS scores of 0–2, 29 (16.9%) a score of 3, 1 (0.6%) a score of 4, 1 (0.6%) a score of 5, and 3 (1.7%) a score of 6. Cerebrovascular events occurred 8 or more years after surgery in 6 patients (3.4%), that is, 6 hemorrhages and 3 infarctions. The cumulative risk of late-onset stroke at 10, 20, and 30 years after surgical intervention was 0.8%, 6.3%, and 10.0%, respectively.

Conclusions

This long-term survey demonstrated that most surgically treated pediatric patients with MMD maintain good ADL outcomes. However, a significant number of new cerebrovascular events occurred more than 10 years after the initial surgery. Additional follow-up will help to identify which events may occur during the adult years of patients treated as children.

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Tadashi Nariai, Katsushige Sato, Kimiyoshi Hirakawa, Yoshihisa Ohta, Yoji Tanaka, Kiichi Ishiwata, Kenji Ishii, Kohtaro Kamino and Kikuo Ohno

Object

Intrinsic optical signals in response to somatosensory stimuli were intraoperatively recorded during brain tumor surgery. In the present study, the authors report on the use of this technique as an intraoperative guide for the safe resection of tumors adjacent to or within the sensorimotor cortex.

Methods

In 14 patients with tumors adjacent to or within the sensorimotor cortex, intrinsic optical signals in response to somatosensory stimuli were recorded by illuminating the brain surface with Xe white light and imaging the reflected light passing through a bandpass filter (605 nm). Results were compared with intraoperative recordings of sensory evoked potentials in all 14 patients and with noninvasive mapping modalities such as magnetoencephalography and positron emission tomography in selected patients. In all but two patients, the somatosensory optical signals were recorded on the primary sensory cortex. Optical signals elicited by stimulation of the first and fifth digits and the three branches of the trigeminal nerve were recorded at different locations on the sensory strip. This somatotopic information was useful in determining the resection border in patients with glioma located in the sensorimotor cortex.

Conclusions

Optical imaging of intrinsic signals is a useful technique with superior spatial resolution for delineating the somatotopic representation of human primary sensory cortex. Furthermore, it can be used as an intraoperative monitoring tool to improve the safety and accuracy of resections of brain tumors adjacent to or within the sensorimotor cortex.

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Takashi Sugawara, Masaru Aoyagi, Takahiro Ogishima, Yoshihisa Kawano, Masashi Tamaki, Tomoyuki Yano, Atsunobu Tsunoda, Kikuo Ohno, Taketoshi Maehara and Seiji Kishimoto

OBJECT

The majority of sinonasal malignancies present with advanced disease, and cure rates are generally poor. Surgical extirpation remains the mainstay of treatment. In cases of sinonasal malignancy with orbital apex extension, gross-total tumor resection requires orbital exenteration and bony skull base resection around the orbital apex to provide sufficient margins. In this retrospective study, the authors describe their surgical strategy in and technique for orbital exenteration with orbital apex resection in patients at Tokyo Medical and Dental University who had sinonasal malignancy with orbital apex extension. They also analyzed the clinical features of and the results in these patients.

METHODS

Between February 2001 and August 2012 at the authors' institution, sinonasal malignancy with orbital apex extension was treated using craniofacial tumor resection with orbital exenteration including skull base bone around the orbital apex. The authors describe this technique and analyze the surgical indications, extent of resection, primary tumor location, outcome, pathological findings, and neoadjuvant and adjuvant therapies of the patients who underwent the technique.

RESULTS

The patients consisted of 12 men and 3 women with a mean age of 47.7 years (range 14–79 years). The longest postoperative follow-up was 9.5 years, and the shortest was 0.67 year (mean 3.0 years). Tumor originated at the ethmoid sinus in 6 patients (40%), maxillary sinus in 5 (33%), nasal cavity in 2 (13%), and orbital cavity and maxillary bone in 1 patient each (7%). Histological analysis of tumor specimens revealed squamous cell carcinoma in 9 patients (60%), rhabdomyosarcoma in 2 (13%), and small cell carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and Ewing sarcoma in 1 patient each (7%). Two patients experienced recurrences at 1 and 5 months after treatment; these patients died at 5 and 10 months after surgery, respectively. Estimated 5-year recurrence-free survival (RFS) was 86.7%, and estimated 5-year overall survival (OS) was 86.2%; there was no perioperative mortality. None of the patients had new neurological deficits as a result of the surgery, but 5 patients suffered infectious complications from the graft transplanted into the cavity after resection. There were no other perioperative complications.

CONCLUSIONS

These authors are the first to describe a technique for extended orbital exenteration with orbital apex skull base resection. The technique provided sufficient margins for gross-total resection of the sinonasal malignancy with orbital apex extension. The estimated 5-year OS and RFS rates were high, and the perioperative complication rate was acceptably low, demonstrating the safety and efficacy of this technique.

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Tadashi Nariai, Yoji Tanaka, Hiroaki Wakimoto, Masaru Aoyagi, Masashi Tamaki, Kiichi Ishiwata, Michio Senda, Kenji Ishii, Kimiyoshi Hirakawa and Kikuo Ohno

Object

The authors retrospectively analyzed the data obtained in patients who had undergone l-[methyl-11C] methionine (MET)—positron emission tomography (PET) studies to clarify the relationship between MET uptake and tumor biological features and to discuss the clinical usefulness of MET-PET studies.

Methods

One hundred ninety-four patients with cerebral glioma or suspected glioma underwent PET scanning 20 minutes after injection of MET, whose uptake into the tumor was expressed as a ratio to contralateral healthy brain tissue (T/N ratio). Analyses were performed to determine how MET uptake correlated with tumor pathological features and prognosis. The T/N ratios before and after various treatments were also examined.

There were significant differences in the T/N ratio among the nonneoplastic lesions, low-grade gliomas, and malignant gliomas. Furthermore, there were significant correlations between patient survival and pretreatment T/N ratios. Among patients with malignant gliomas, a significant difference in survival was observed between cases with and without postoperative tumor remnant based on elevated MET uptake. The MET uptake was heterogeneous even among the homogeneous tumor areas demonstrated on MR imaging. Malignant pathological features were detected in the areas with the highest MET uptake. The effectiveness of radiotherapy or chemotherapy was expressed as a significantly decreased T/N ratio in some of the tumor types.

Conclusions

The ability of MET-PET to reflect the biological nature of gliomas makes it an excellent method for monitoring active tumor tissue, and treatments based on its findings should provide a powerful clinical protocol in the course of glioma therapy.