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Jun Harada, Akira Takaku, Shunro Endo, Naoya Kuwayama and Osamu Fukuda

✓ Normal cerebral blood flow (CBF), critical CBF at a flat reading of the electroencephalogram (EEG), and reversibility of the flat EEG after reperfusion were investigated in a total of 59 pigs, including seven newborns (1 to 3 days of age), 38 juveniles (1 month old), and 14 adults (7 months old). The CBF was determined by the hydrogen clearance method; the EEG was recorded continuously and a power spectrum analysis was performed. Cerebral ischemia was produced by occlusion of both common carotid arteries and induction of hypotension (approximately 50 mm Hg). The flat EEG reversibility was investigated for 3 hours after reperfusion. As parameters of brain development, the neuronal density and the time at which the S-100 protein appeared in the brain were examined.

Normal CBF was highest in neonatal pigs and decreased with age. The critical CBF at a flat EEG was lowest in newborn pigs and was elevated with development of the brain. Tolerance against cerebral ischemia was greatest in newborn pigs.

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Naoya Kuwayama, Shinichiro Takahashi, Makoto Sonobe and Kyoichi Sugita

✓ Spontaneous extradural hematomas are rare and may be caused by pericranial infections, bleeding tendencies, or vascular abnormalities of the dura mater. The authors describe a case of spontaneous bilateral extradural hematomas assumed to be caused by a bleeding tendency with hypofibrinogenemia. A brief review of the literature is reported.

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Shunro Endo, Naoya Kuwayama, Akira Takaku and Michiharu Nishijima

Object. The goal of this study was to evaluate the efficacy of direct packing of the isolated sinus (occluded both distally and proximally) in patients with dural arteriovenous fistulas (AVFs) of the transverse—sigmoid sinus.

Methods. Eight patients were included in this study. There were seven men and one woman, ranging in age from 47 to 75 years (mean 60.4 years). Five patients presented with intracranial hemorrhage or venous infarction, one with convulsions, and two with pulsatile tinnitus. Prominent retrograde cortical venous drainage due to sinus isolation was angiographically demonstrated in all patients. All patients were treated by a small craniotomy and direct sinus packing with microcoils; the procedure was performed with the aid of digital subtraction angiography. Five patients were pretreated with transarterial embolization to reduce arterial inflow before the procedure, and intrasinus pressure and sinus blood gases were monitored throughout the operation. Postsurgery, the dural AVF was completely obliterated in all patients. The sinus pressure was 29 to 58% of systemic blood pressure, and sinus blood gas levels were purely arterial before packing. There was no morbidity related to direct sinus packing; however, one patient died as a result of acute myocardial infarction. Over a follow-up period ranging from 1 to 5 years, a faint asymptomatic dural AVF recurred in one patient on the cortex adjacent to the occluded sinus but regressed spontaneously within 1 year.

Conclusions. Direct sinus packing was found to be highly effective for the treatment of dural AVFs that empty into the isolated sinus. Measurement of changes in sinus pressure and sinus blood gas levels was useful for monitoring the progress of direct sinus packing.

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Naoya Kuwayama, Akira Takaku, Michiharu Nishijima, Shunro Endo and Masato Hirao

✓ Two cases of multiple dural arteriovenous malformations (AVM's) in different locations are reported. One patient was diagnosed as having a dural AVM involving the right cavernous sinus that disappeared spontaneously 4 months after onset of symptoms. After an interval of 4 months, another dural AVM appeared involving the right lateral sinuses (transverse and sigmoid sinuses) with occlusion of the right sigmoid sinus. In the other patient, multiple dural AVM's were demonstrated on angiography, one involving the cavernous sinus and the other the left lateral sinus. The frequency of multiple occurrence and possible mechanisms of sinus occlusion are discussed.

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Michiharu Nishijima, Akira Takaku, Shunro Endo, Naoya Kuwayama, Fumitomo Koizumi, Hideji Sato and Kenji Owada

✓ Controversy persists concerning the pathogenesis of dural arteriovenous malformations (AVM's) and whether they are congenital or acquired. Furthermore, it remains undetermined whether the lesion is located in the sinus itself or within the sinus wall. In order to elucidate the pathogenesis of dural AVM's of the lateral and sigmoid sinuses, histopathological profiles of this disease were studied in serial sections of completely resected lesions from three patients. The essential lesion was histologically confirmed to be a dural arteriovenous fistula within the wall of the venous sinuses. The etiology process of this disease and its progression were evaluated.

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Daina Kashiwazaki, Naoki Akioka, Naoya Kuwayama, Tomohide Hayashi, Kyo Noguchi, Kortaro Tanaka and Satoshi Kuroda

OBJECTIVE

The roles of endothelial progenitor cells (EPCs) in the development of carotid plaque are still obscure. This study aimed to clarify this by assessing the histological findings of specimens obtained from carotid endarterectomy.

METHODS

This study included 34 patients who underwent carotid endarterectomy. MR imaging was performed to semiquantitatively analyze the components of the carotid plaques in all patients. The surgical specimens were subjected to immunohistochemistry. The distributions of the CD34-, CD133-, VEGF-2R–positive cells in the carotid plaques were precisely analyzed, and their number was quantified. Simultaneously, the CD34-positive microvessels were localized.

RESULTS

The plaque component was judged as lipid-rich plaque in 19 patients, intraplaque hemorrhage (IPH) in 11 patients, and fibrous plaque in 4 patients. The CD34-positive microvessels were densely distributed in the plaque shoulder and interface-to-media regions. The CD34-, CD133-, and VEGF-2R–positive cells were mainly localized around the CD34-positive microvessels. The number of CD34-positive microvessels significantly correlated with the number of CD34-, CD133-, and VEGF-2R–positive cells (R = 0.308, p = 0.009; R = 0.324, p = 0.006; and R = 0.296, p = 0.013, respectively). Vulnerable plaques (lipid-rich and IPH) had significantly higher numbers of the CD34-positive microvessels (p = 0.007) and CD34-, CD133-, and VEGF-2R–positive cells than fibrous plaques (p = 0.031, p = 0.013, and p = 0.002).

CONCLUSIONS

These findings strongly suggest that neovascularization in the plaque shoulder and interface-to-media regions may play a key role in delivering EPCs from the peripheral blood to the carotid plaque, promoting the growth of carotid plaque. Furthermore, the invaded EPCs, especially the CD133-positive immature EPCs, may be related to plaque vulnerability.

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Daina Kashiwazaki, Masaki Koh, Haruto Uchino, Naoki Akioka, Naoya Kuwayama, Kyo Noguchi and Satoshi Kuroda

OBJECTIVE

The relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed.

METHODS

This study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1α)–, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)–positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels.

RESULTS

Plaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2–, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1α–positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum luminal diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1α–positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous).

CONCLUSIONS

The present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.

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Shusuke Yamamoto, Satoshi Hori, Daina Kashiwazaki, Naoki Akioka, Naoya Kuwayama and Satoshi Kuroda

OBJECTIVE

This study aimed to assess longitudinal changes in the collateral channels originating from the lenticulostriate artery (LSA), posterior communicating artery (PCoA), and anterior and posterior choroidal arteries (AChA and PChA, respectively) during disease progression and/or aging. The impact of collateral channels on onset type was also examined.

METHODS

This study included 71 involved hemispheres in 41 patients with moyamoya disease. The disease was categorized into 6 stages according to Suzuki’s angiographic staging system. The degree of development of each moyamoya vessel was categorized into 3 grades.

RESULTS

The LSA started to dilate in stage 2, showed the most prominent development in stage 3, and decreased in more advanced stages (p < 0.001). The AChA most notably developed in stage 3 and gradually shrank (p = 0.04). The PCoA started to dilate in stage 3 and showed the most prominent development in stage 4 (p = 0.03). The PChA started to dilate in stage 3 and showed the most prominent development in stages 4 to 5 (p < 0.001). Patient age was negatively related to LSA development (p = 0.01, R = 0.30) and was positively associated with the abnormal dilation and extension of the PCoA (p = 0.02, R = 0.28) and PChA (p < 0.001, R = 0.45). The PCoA, AChA, and PChA more distinctly developed in hemispheres with intracerebral or intraventricular hemorrhage than in hemispheres with ischemic stroke or transient ischemic attack (p < 0.001, p = 0.03, and p = 0.03, respectively).

CONCLUSIONS

This study suggests that the collateral channels through moyamoya vessels longitudinally shift from the anterior to posterior component during disease progression and aging, which may be closely related to the onset of hemorrhagic stroke in adult moyamoya disease.