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Yasushi Takagi, Ken-Ichiro Kikuta, Kazuhiko Nozaki, Motoaki Fujimoto, Junya Hayashi and Nobuo Hashimoto

Object

The expression and localization of phosphorylated Fas-associated death domain protein (pFADD) and cleaved caspase-8 was examined in human cerebral arteriovenous malformations (AVMs). The authors focused on the perinidal parenchyma to clarify the effect of AVMs on perinidal brain tissue.

Methods

Seventeen cerebral AVMs were analyzed using immunohistochemical methods. Specimens were removed from patients during surgical procedures. The characteristics of the areas that stained positively for pFADD or cleaved caspase-8 were also assessed using an image analysis system. Eleven (65%) of the 17 lesions demonstrated anti-pFADD immunoreactivity and 12 (71%) showed anti–cleaved caspase-8 immunoreactivity. The immunoreactive cells in the perinidal parenchyma demonstrated obvious neuronal morphological characteristics.

The characteristics of pFADD-positive and cleaved caspase-8–positive areas were assessed using the image analysis system. The mean distance from the nidus adjacent to either area was not affected by preoperative hemorrhage. The neuronal densities of pFADD-positive and cleaved caspase-8–positive areas were analyzed using the same system. The density of the control area (samples that were pFADD-negative and cleaved caspase-8 negative) was significantly higher when compared with that of pFADD-positive and cleaved caspase-8–positive areas (p < 0.05). The expressions of cleaved caspase-9, cleaved poly(adenosine diphosphate–ribose) polymerase, and apoptotic cells were analyzed using the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling method.

Conclusions

Neuronal areas that stained positively for pFADD and cleaved caspase-8 existed around the nidus of AVMs. In these areas, the neuronal density was lower than that in the other parenchyma around the AVM. Neuronal loss around the nidus may be the origin of brain dysfunction around AVMs.

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Shigeki Yamada, Yasushi Takagi, Kazuhiko Nozaki, Ken-ichiro Kikuta and Nobuo Hashimoto

Object

The aim of this study was to identify the natural history of untreated cerebral arteriovenous malformations (AVMs) and the risk factors for subsequent hemorrhage after an initial AVM diagnosis.

Methods

The authors studied 305 consecutive patients with AVMs at the Kyoto University Hospital between 1983 and 2005. These patients were followed up until the first subsequent hemorrhage, the start of any treatment, or the end of 2005. Possible risk factors that were investigated included age at initial diagnosis, sex, type of initial presentation, size and location of the AVM nidus, and the venous drainage pattern. Subsequent hemorrhage occurred in 26 patients from the hemorrhagic group during 380 patient–years, and in 16 patients from the nonhemorrhagic group during 512 patient–years.

Results

The annual bleeding rate in the hemorrhagic group was 6.84% after the initial hemorrhage; however, that rate decreased in the first 5 years (15.42% in the first year, 5.32% in the subsequent 4 years, and 1.72% in more than 5 years). In the nonhemorrhagic group (annual bleeding rate of 3.12%), the patients initially presenting with headaches (annual bleeding rate of 6.48%) or asymptomatic presentations (annual bleeding rate of 6.44%) had a higher risk for subsequent hemorrhage. Conversely, those patients presenting with seizures (annual bleeding rate of 2.20%) or neurological deficits (annual bleeding rate of 1.73%) had a lower risk. A significantly increased risk (p < 0.05) of rebleeding was found among children (hazard ratio [HR] = 2.69), females (HR = 2.93), or patients with deep-seated AVMs (HR = 3.07).

Conclusions

Children, females, and patients with deep-seated AVMs had a threefold increased risk of rebleeding after an initial cerebral AVM. This increased risk was highest in the first year after the initial hemorrhage, and thereafter gradually decreased.

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Yasushi Takagi, Ken-ichiro Kikuta, Kazuhiko Nozaki, Keiko Sawamura and Nobuo Hashimoto

✓With the use of indocyanine green (ICG) as a novel fluorescent dye, and its integration into a compact system that takes advantage of modern video technology, fluorescence angiography has recently reemerged as a viable option. In this report, the authors show the efficacy of ICG videoangiography in the case of a child with a cerebral arteriovenous malformation (AVM). In this case, the ICG videoangiography shows residual nidus of diffuse-type AVM. This is a safe and simple method that can be used to assess the microcirculation of the brain. The ICG videoangiography is helpful in resecting residual cerebral AVM, especially in cases of diffuse-type AVM.

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Ken-ichiro Kikuta, Yasushi Takagi, Yoshiki Arakawa, Susumu Miyamoto and Nobuo Hashimoto

✓ The authors present the case of a 6-year-old girl with typical absence epilepsy induced by hyperventilation associated with moyamoya disease (MMD). A diffuse 3-Hz spike-and-wave complex induced by hyperventilation was apparent on an electroencephalogram, and her seizures were intractable to medication. Significant ischemia in the bilateral frontal lobes was present. The epilepsy disappeared after superficial temporal artery–middle cerebral artery anastomosis with encephalomyosynangiosis on both sides. In the treatment of children with intractable absence epilepsy, the possibility of underlying MMD and indications that revascularization surgery may be needed should be taken into consideration.

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Ken-ichiro Kikuta, Kazuhiko Nozaki, Jun A. Takahashi, Susumu Miyamoto, Haruhiko Kikuchi and Nobuo Hashimoto

Object. The aim of this study was to propose criteria to determine whether complete resection of cavernous malformations in the brainstem had been achieved.

Methods. The authors retrospectively analyzed data in 10 patients harboring a single cavernous malformation who had presented with hemorrhagic symptoms and had been followed up for longer than 2 years postsurgery. The study population consisted of five male and five female patients ranging in age from 13 to 57 years (mean 36.8 years). When preoperative magnetic resonance (MR) images demonstrated the lesion as a homogeneous hyperintense mass, the surgery was defined as complete or incomplete based on intraoperative findings. When preoperative MR images revealed other findings, complete resection was determined according to whether postoperative MR imaging results demonstrated lesions distinct from the peripheral hemosiderin rim. Among the 13 operations in this series, nine resulted in complete resection and were associated with no postoperative clinical relapse of hemorrhage, whereas four operations resulted in incomplete resection and were correlated with postoperative recurrent hemorrhage. The seven patients in whom the outcome of the initial operation was complete demonstrated good neurological recovery in the long-term follow-up period, whereas the three patients in whom the outcome of the initial surgery was judged to be incomplete showed inadequate neurological recovery due to recurrent hemorrhage.

Conclusions. The criteria proposed in this study to evaluate surgical treatment may be a reliable means of predicting the recurrence of hemorrhage postoperatively.

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Hiroaki Takeuchi, Norichika Hashimoto, Ryuhei Kitai, Toshihiko Kubota and Ken-ichiro Kikuta

Object

Glioblastomas multiforme (GBM) contain a higher number of α-smooth muscle actin (SMA)–positive vascular smooth muscle cells (VSMCs) than those in the respective normal neuronal tissue. The role of VSMCs during angiogenesis is unclear, and it is also uncertain whether and to what extent angiogenic factors might be involved in GBM VSMCs. In GBMs, the contribution of VSMCs in angiogenesis accompanying endothelial proliferation and the correlation of VSMC proliferation with vascular endothelial growth factor (VEGF) expression were examined using an immunohistochemical method.

Methods

The examined material, including surrounding brain tissue, came from 12 cases (6 men and 6 women) with classic GBM. Microvessel densities (MVDs) of CD31-immunoreactive vessels (CD31-MVD) and SMA-immunoreactive vessels (SMA-MVD) were obtained in areas selected from white matter, boundary, tumor (concentrated area of tumor cells), and perinecrosis. Subsequently, the SMA-MVD/CD31-MVD (SMA/CD31) rate, representing the percentage of vessels with VSMCs in the region, was calculated in each area. The VEGF immunoreactivity of tumor cells was examined, and cases were divided into 2 groups: < 30% VEGF expression of tumor cells (low VEGF group) and > 30% VEGF expression of tumor cells (high VEGF group).

Results

The SMA/CD31 rate of the boundary was significantly lower than that of the tumor (p < 0.005) and perinecrosis (p < 0.001). The SMA/CD31 rate of the high VEGF group was significantly higher than that of the low VEGF group (p < 0.05) in the tumor.

Conclusions

In GBMs, the transformation and proliferation of VSMCs may accompany neovascularization and may also be induced by angiogenic factors.

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Ken-ichiro Kikuta, Masato Hojo, Masanori Gomi, Nobuo Hashimoto and Kazuhiko Nozaki

✓ The authors report the case of a 25-year-old man with a thoracolumbar extradural arachnoid cyst who underwent expansive duraplasty. Symptoms, preoperative magnetic resonance imaging features, and intraoperative findings suggested the involvement of entrapment neuropathy in the manifestation of symptoms. To the authors’ knowledge, this case represents the first evidence that expansive duraplasty can achieve complete resolution of the symptoms in a patient with a spinal extradural arachnoid cyst. The results indicate that duraplasty may be an alternative option in cases in which complete resection of the lesion is difficult and widening of the dural sac is necessary at surgery.

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Hidetaka Arishima, Yoshifumi Higashino, Shinsuke Yamada, Ayumi Akazawa, Hiroshi Arai, Kenzo Tsunetoshi, Ken Matsuda, Toshiaki Kodera, Ryuhei Kitai, Kousuke Awara and Ken-ichiro Kikuta

The authors describe a new procedure to detect the tiny dural hole in patients with superficial siderosis (SS) and CSF leakage using a coronary angioscope system for spinal endoscopy and selective CT myelography using a spinal drainage tube. Under fluoroscopy, surgeons inserted the coronary angioscope into the spinal subarachnoid space, similar to the procedure of spinal drainage, and slowly advanced it to the cervical spine. The angioscope clearly showed the small dural hole and injured arachnoid membrane. One week later, the spinal drainage tube was inserted, and the tip of the drainage tube was located just below the level of the dural defect found by the spinal endoscopic examination. This selective CT myelography clarifies the location of the dural defect. During surgery, the small dural hole could be easily located, and it was securely sutured. It is sometimes difficult to detect the actual location of the small dural hole even with thin-slice MRI or dynamic CT myelography in patients with SS. The use of a coronary angioscope for the spinal endoscopy combined with selective CT myelography may provide an effective examination to assess dural closure of the spinal dural defect with SS in cases without obvious dural defects on conventional imaging.

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Ken-Ichiro Kikuta, Yasushi Takagi, Kazuhiko Nozaki, Takashi Hanakawa, Tsutomu Okada, Nobuhro Mikuni, Yukio Miki, Yasutaka Fushimi, Akira Yamamoto, Keisuke Yamada, Hidenao Fukuyama and Nobuo Hashimoto

Object. The aim of this study was to investigate the incidence of asymptomatic microbleeds (MBs) in patients with moyamoya disease (MMD) by using a 3-tesla magnetic resonance (MR) imaging unit.

Methods. Data on 63 patients hospitalized with MMD between 1999 and 2004 were retrospectively examined to determine the incidence of asymptomatic MBs. Gradient-echo T2*-weighted MR imaging studies obtained using 3- and 1.5-tesla units were available in 25 patients. These patients consisted of five men and 20 women, ranging in age from 17 to 66 years (mean age 41 ± 14 years). Ischemic MMD was diagnosed in 18 patients, and hemorrhagic MMD in seven. The incidence of MBs was also evaluated using the same 3-tesla MR imaging unit in 34 healthy volunteers including seven men and 27 women, ranging in age from 18 to 71 years (mean age 33 ± 12 years). Using the 3-tesla MR unit, asymptomatic MBs were demonstrated in 11 patients (44%); they were detected in seven patients (28%) by using the 1.5-tesla unit. In the 3-tesla MR studies in healthy individuals, MBs were found in two patients (5.8%). Based on 3-tesla MR studies, the incidence of MBs was significantly higher in patients with MMD compared with that in healthy individuals. Asymptomatic MBs were demonstrated in eight (44%) of 18 patients with ischemic MMD and three (43%) of seven patients with hemorrhagic MMD.

Conclusions. Microbleeds are significantly more common in patients with MMD than in healthy individuals regardless of the disease type. The evaluation of MBs with T2*-weighted 3-tesla MR imaging might contribute to the treatment of MMD.

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Nobuhiro Mikuni, Tsutomu Okada, Rei Enatsu, Yukio Miki, Takashi Hanakawa, Shin-ichi Urayama, Kenichiro Kikuta, Jun A. Takahashi, Kazuhiko Nozaki, Hidenao Fukuyama and Nobuo Hashimoto

Object

The authors evaluated the clinical impact of combining functional neuronavigation with subcortical electrical stimulation to preserve motor function following the removal of brain tumors.

Methods

Forty patients underwent surgery for treatment of brain tumors located near pyramidal tracts that had been identified by fiber tracking. The distances between the electrically stimulated white matter and the pyramidal tracts were measured intraoperatively with tractography-integrated functional neuronavigation, and correlated with subcortical motor evoked potentials (MEPs) and clinical symptoms during and after resection of the tumors.

Motor function was preserved after appropriate tumor resection in all cases. In 18 of 20 patients, MEPs were elicited from the subcortex within 1 cm of the pyramidal tracts as measured using intraoperative neuronavigation. During resection, improvement of motor weakness was observed in two patients, whereas transient mild motor weakness occurred in two other patients. In 20 patients, the distances between the stimulated subcortex and the estimated pyramidal tracts were more than 1 cm, and MEPs were detected in only three of these patients following stimulation.

Conclusions

Intraoperative functional neuronavigation and subcortical electrical stimulation are complementary techniques that may facilitate the preservation of pyramidal tracts around 1 cm of resected tumors.