De novo formation and rupture of an intracranial aneurysm 10 months after normal findings on conventional magnetic resonance angiography in a patient with no history of intracranial lesions -case report-

A 40-year-old male smoker presented with a ruptured saccular aneurysm that formed de novo 10 months after normal magnetic resonance (MR) angiography findings. Computed tomography of the head at the second admission showed subarachnoid hemorrhage in the interhemispheric fissure and anterior basal cistern. MR and conventional cerebral angiography revealed an aneurysm arising from the anterior communicating artery (AcomA). MR angiography performed 10 months earlier, when he experienced transient loss of consciousness, revealed no anomalies at the AcomA. Intraoperatively, the de novo aneurysm was found to be a typical saccular aneurysm with a fragile wall.


解離性後大脳動脈瘤の臨床的検討 ー特に治療法および予後についてー

解離性後大脳動脈瘤の臨床的検討 ー特に治療法および予後についてー


Akt2 and Akt3 play a pivotal role in malignant gliomas

Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well understood. Therefore, we examined the protein and mRNA expression patterns of Akt isoforms in tissues from human astrocytomas, glioblastomas, and non-neoplastic regions. We also explored the biological role of each Akt isoform in malignant glioma cells using RNA interference-mediated knock-down and the over-expression of plasmid DNA of each isoform. The expression of Akt1 protein and mRNA was similar in glioma and normal control tissues. Although the protein and mRNA level of Akt2 increased with the pathological grade of malignancy, the expression of Akt3 mRNA and protein decreased as the malignancy grade increased. In U87MG, T98G, and TGB cells, the down-regulation of Akt2 or Akt3 by RNA interference reduced the expression of the phosphorylated form of Bad, resulting in the induction of caspase-dependent apoptosis. Akt1 knock-down did not affect cell growth or survival. We first demonstrate that the over-expression of Akt2 or Akt3 down-regulated the expression of the other protein and that endogenous Akt3 protein showed high kinase activity in U87MG cells. Our data suggest that Akt2 and Akt3 play an important role in the viability of human malignant glioma cells. Targeting Akt2 and Akt3 may hold promise for the treatment of patients with gliomas.


Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats.

OBJECTIVE: Phosphodiesterase-4 (PDE-4) is a cyclic adenosine monophosphate-specific enzyme involved in various inflammatory diseases. We studied its role in and the effect of ibudilast, which predominantly blocks PDE-4, on rat cerebral aneurysms. METHODS: Cerebral aneurysms were induced at the anterior cerebral artery-olfactory artery bifurcation of female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The effect of ibudilast (30 or 60 mg/kg/d for 3 months) on their cerebral aneurysms was studied by morphological and immunohistochemical assessment and quantitative real-time polymerase chain reaction assay. In our in vitro study, we grew endothelial cells stimulated by angiotensin II under estrogen-free conditions and examined the effect of ibudilast on PDE-4 activation and the cyclic adenosine monophosphate level. RESULTS: Morphological evaluation using vascular corrosion casts showed ibudilast significantly suppressed cerebral aneurysms in a dose-dependent manner. In rats with induced cerebral aneurysms, the gene and protein expression of PDE-4 was high, and endothelial leukocyte adhesion molecules (P-selectin, intracellular adhesion molecule 1, and vascular adhesion molecule 1), matrix metalloproteinase-9, and tumor necrosis alpha were expressed. Macrophage migration was also increased. Treatment with ibudilast down-regulated these molecules, suppressed macrophage migration into the aneurysm wall, and inhibited PDE-4 activation and the elevation of cyclic adenosine monophosphate in endothelial cells. CONCLUSION: These results suggest that blocking of PDE4 is associated with the reduction of inflammation-related molecules and macrophage migration, thereby reducing the progression of cerebral aneurysms. It may represent a new conservative therapy to treat patients with cerebral aneurysms.


Pilomyxoid astrocytoma of the cervical spinal cord successfully treated with chemotherapy - case report -

A 15-month-old girl presented with a spinal pilomyxoid astrocytoma manifesting as a 3-month history of dysphagia. Magnetic resonance imaging showed an intramedullary mass of the cervical spinal cord at C1-C6 with syringobulbia. She underwent partial removal of the tumor and received postoperative chemotherapy with cisplatin and etoposide. The tumor completely responded to the treatment and has not relapsed for 64 months. Pilomyxoid astrocytoma frequently occurs in the opticohypothalamic regions but is rare in the spine. The present case suggests that surgery followed by chemotherapy with cisplatin and etoposide may be an effective therapeutic option for pilomyxoid astrocytoma of the cervical spinal cord.


増大する器質化慢性硬膜下血腫の診断と治療:症例報告

増大する器質化慢性硬膜下血腫の診断と治療:症例報告


Reversibility of ischemic findings on 3-T T2*-weighted imaging after emergency superficial temporal artery-middle cerebral artery anastomosis in patients with progressive ischemic stroke.

Vascular ischemic signs, i.e. multiple hypointense vessels in the ischemic territory, were identified by gradient echo-type 3-T T(2)*-weighted magnetic resonance (MR) imaging in 3 patients with acute ischemia due to major vessel occlusion. Emergency superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis was performed in 2 patients with progressive stroke caused by bleeding-type moyamoya disease or severe MCA stenosis. Both patients were initially treated conservatively, but their neurological signs deteriorated. 3-T T(2)*-weighted MR imaging detected funicular low signals in both patients indicating enhancement of cortical vessels or medullary veins. The area of the vascular ischemic signs was almost the same or smaller than the hypoperfusion area on perfusion-weighted MR imaging or single-photon emission computed tomography. Postoperatively, the vascular ischemic signs disappeared in both patients, suggesting a relationship with severe ischemia due to high-risk misery perfusion. Their postoperative course was uneventful, and MR imaging revealed no new cerebral ischemic lesions or cerebral hyperperfusion. The patient without surgery developed cerebral infarction in the area of the vascular ischemic signs. Vascular ischemic signs detected by 3-T T(2)*-weighted MR imaging may represent a new predictor of high-risk misery perfusion, and may disappear after STA-MCA anastomosis performed in the subacute stage.


チクロピジンからクロピドグレルへの切り替えによる有効性・安全性の検討

チクロピジンからクロピドグレルへの切り替えによる有効性・安全性の検討


Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats.

Activation of the renin-angiotensin (Ang)-aldosterone system is involved in the pathology of vascular diseases. Although the blockade of the mineralocorticoid receptor protects against vascular diseases, its role in cerebral aneurysms remains to be elucidated. We treated female rats subjected to renal hypertension, increased hemodynamic stress, and estrogen deficiency for 3 months with the mineralocorticoid receptor blocker eplerenone (30 or 100 mg/kg per day) or vehicle (vehicle control). Eplerenone reduced the incidence of cerebral aneurysms and saline intake without lowering of the blood pressure. In the aneurysmal wall, the production of Ang II and nitrotyrosine was increased. The mRNA levels of Ang-converting enzyme 1 and NADPH oxidase subunits NOX4, Rac1, monocyte chemoattractant protein 1, and matrix metalloproteinase 9 were increased. Eplerenone brought about a reduction in these molecules, suggesting that mineralocorticoid receptor blockade suppresses cerebral aneurysm formation by inhibiting oxidative stress, inflammatory factors, local renin-Ang system activation, and saline intake. Other female rats implanted with pellets of the mineralocorticoid receptor agonist deoxycorticosterone acetate manifested a high incidence of cerebral aneurysm formation and the upregulation of molecules related to oxidative stress, inflammatory factors, and the local renin-Ang system; their saline intake was increased. We demonstrate that mineralocorticoid receptor activation at least partly contributes to the pathogenesis of cerebral aneurysms.


Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats

Epidemiological data indicate a high incidence of cerebral aneurysms in postmenopausal women. To elucidate the pathogenesis of cerebral aneurysms, we focused on the contribution of endothelial damage in rats. We induced estradiol deficiency by oophorectomy (OVX), hypertension, or both, and hemodynamic stress in 7-week-old female Sprague-Dawley rats. They were then given hormone-replacement therapy with 17beta-estradiol or an angiotensin II type 1 receptor blocker (ARB). The effects of estradiol, angiotensin II type 1 receptor blocker, or both on cultured endothelial cells were also examined. The number of anomalously shaped endothelial cells was higher in OVX than hypertensive rats (P < 0.05). Rats subjected to hypertension and OVX exhibited a marked increase in the incidence of saccular cerebral aneurysms. Estradiol or angiotensin II type 1 receptor blocker treatment reduced this incidence (P < 0.05). The endothelial nitric oxide synthase (eNOS) mRNA level in the intracranial artery of OVX and hypertensive and OVX rats was low (P < 0.05). Immunohistochemically, the expression of eNOS and estrogen receptor alpha (ERalpha) in the vascular wall of hypertensive and OVX rats was decreased; angiotensin II and the nicotinamide adenine dinucleotide phosphate oxidase subunits nicotinamide adenine dinucleotide phosphate oxidase 4 and p22phox were strongly expressed in cerebral aneurysms. In the absence of estradiol, eNOS was downregulated and nicotinamide adenine dinucleotide phosphate oxidase expression was increased in endothelial cells; angiotensin II augmented these phenomena. The regulation of eNOS was mediated by ERalpha. These results suggest that estrogen deficiency induces endothelial dysfunction and reactive oxygen species generation, triggering endothelial damage that leads to cerebral aneurysms and that hypertension is an additional risk factor. A therapy targeted at the endothelium and management of hypertension may help to prevent cerebral aneurysms.


Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease

Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinson's disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% +/- 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms.


Retinal artery embolization during carotid angioplasty and carotid artery stenting -case report-

A 69-year-old man presented with a rare case of retinal artery embolization, which occurred as a complication of carotid angioplasty and carotid artery stenting performed for recurrent cerebral infarction. Magnetic resonance imaging and angiography showed right internal carotid artery stenosis with ulceration. Carotid angioplasty and carotid artery stenting were performed using the distal protection system with the PercuSurge GuardWire. However, just after dilation, the patient complained of ocular pain and blurred vision on the right, which was subsequently diagnosed as retinal artery embolization. Heparin was given for 15 hours after stenting, and aspirin and ticlopidine medication were continued. The patient received hyperbaric oxygen therapy for 1 week. The patient's blurred vision gradually improved, but visual field defect remained. Debris was probably flushed into the external carotid artery, and passed through an anastomosis into the ophthalmic artery, resulting in retinal artery embolization.


Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasmininogen activator

Intracerebral hemorrhage, induced by recombinant tissue plasminogen activator (rtPA) in ischemic stroke, is attributable to the increased activity of matrix metalloproteinase-9 (MMP-9). Patients with acute infarct benefit from the neuroprotective drug edaravone, a free radical scavenger. We examined the mechanisms by which edaravone may help to suppress rtPA-induced brain hemorrhage. Male Wistar rats weighing 250 to 280 g were subjected to 3-hour transient middle cerebral artery occlusion (MCAO) and divided randomly into 3 groups. Immediately after reperfusion, 1 group was intravenously injected with 10 mg/kg rtPA, another with rtPA plus 3 mg/kg edaravone, and the 3rd group received no treatment. We assessed the hemorrhage volume and the activity of MMP-9 in the brain 24 hours postischemia. We also studied the activity of MMP-9, its mRNA expression, and nuclear factor-kappa B (NF-kappaB) activity in rtPA-stimulated human microvascular endothelial cells (HBECs). The degree of hemorrhage and the level of endothelial cell-derived MMP-9 were elevated in rats treated with rtPA alone and attenuated in rats treated with rtPA plus edaravone. In rtPA-stimulated HBECs, edaravone suppressed the activity and mRNA expression of MMP-9 in a dose-dependent manner. Edaravone also inhibited NF-kappaB activation. We demonstrate that edaravone inhibits rtPA-induced cerebral hemorrhage in the ischemic brain of rats via the inhibition of MMP-9 expression in vivo, which is substantiated by inhibition of MMP-9 expression and NF-kappaB activation in HBECs. Edaravone may render thrombolytic therapy safer for the administration of rtPA in patients with ischemic stroke.


Promyelocytic leukemia protein induces apoptosis due to caspase-8 activation via the repression of NFkB activation in glioblastoma

Promyelocytic leukemia (PML) protein plays an essential role in the induction of apoptosis; its expression is reduced in various cancers. As the functional roles of PML in glioblastoma multiforme (GBM) have not been clarified, we assessed the expression of PML protein in GBM tissues and explored the mechanisms of PML-regulated cell death in GBM cells. We examined the PML mRNA level and the expression of PML protein in surgical GBM specimens. PML-regulated apoptotic mechanisms in GBM cells transfected with plasmids expressing the PML gene were examined. The protein expression of PML was significantly lower in GBM than in non-neoplastic tissues; approximately 10% of GBM tissues were PML-null. The PML mRNA levels were similar in both tissue types. The overexpression of PML activated caspase-8 and induced apoptosis in GBM cells. In these cells, PML decreased the expression of transactivated forms of NFkappaB/p65, and c-FLIP gene expression was suppressed. Therefore, PML-induced apoptosis resulted from the suppression of the transcriptional activity of NFkappaB/p65. PML overexpression decreased phosphorylated IkappaBalpha and nuclear NFkappaB/p65 and increased the expression of the suppressor of cytokine signaling (SOCS-1). A proteasome inhibitor blocked the reduction of activated p65 by PML. The reduction of PML is associated with the pathogenesis of GBM. PML induces caspase-8-dependent apoptosis via the repression of NFkappaB activation by which PML facilitates the proteasomal degradation of activated p65 and the sequestration of p65 with IkappaBalpha in the cytoplasm. This novel mechanism of PML-regulated apoptosis may represent a therapeutic target for GBM.


Primary anaplastic pleomorphic xanthoastrocytoma with widespread neuroaxis dissemination at diagnosis--a pediatric case report and review of the literature.

We report a 5 year-old boy with primary anaplastic pleomorphic xanthoastrocytoma (PXA) with whole neuroaxis dissemination at diagnosis who experienced the sudden onset of generalized convulsion. Head- and spinal magnetic resonance imaging (MRI) showed widespread gadolinium (Gd)-enhanced lesions extending to the bilateral frontal- and medial temporal lobes and the spinal cord. Subsequent MRI study demonstrated that the lesion size increased without any neurological deterioration. Under a histopathologic diagnosis of anaplastic PXA he underwent adjuvant chemotherapy consisting of 12 cycles of carboplatin and vincristine. The patient is alive without any neurological deficits; follow-up MRI showed that the lesions remained stable during 18 months of chemotherapy. We report a very rare pediatric case of primary anaplastic PXA with dissemination involving the entire neuroaxis at the time of diagnosis.


3T-MRIによる脳血管疾患の画像診断

3T-MRIによる脳血管疾患の画像診断


急性期脳虚血モデルにおけるrt-PA投与時のエダラボンによる脳出血抑制効果

急性期脳虚血モデルにおけるrt-PA投与時のエダラボンによる脳出血抑制効果


副鼻腔内に進展した前頭蓋底部髄膜種の手術

副鼻腔内に進展した前頭蓋底部髄膜種の手術


NST症例におけるワルファリン治療に及ぼす経腸栄養剤のビタミンK含有量の影響の検討


虚血に対するARBの脳保護作用のメカニズム ーin vivoおよびin vitroでの検討ー


硬膜動静脈瘻に対する外科的治療成績とそのpitfall

硬膜動静脈瘻に対する外科的治療成績とそのpitfall


Evaluation of Initial Diffusion-weighted Image Findings in Acute Stroke Patients using a Semiquantitative Score.

We evaluated the usefulness of rating diffusion-weighted images (DWI) using a semiquantitative score modified from the Alberta Stroke Programme Early CT Score (ASPECTS) to predict deterioration of neurological symptoms in patients with hyperacute ischemic stroke who had undergone thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). We examined 22 patients with acute stroke (14 men, 8 women, mean age 72.5 years) treated with intravenous rt-PA. All were assessed using the National Institutes of Health Stroke Scale (NIHSS) and underwent emergent magnetic resonance (MR) imaging within 3 hours and 24 hours of stroke onset. Patients were divided into a deteriorated group (16 patients), in which NIHSS scores were increased after thrombolysis, and a non-deteriorated group (6 patients). We compared the DWI score, ASPECTS, and volume of hyperintense ischemic lesion on DWI (DWI volume) of the 2 groups and examined correlations between these scores and initial NIHSS score or DWI volume. The DWI score and ASPECTS tended to be lower in the deteriorated group than the non-deteriorated group. In addition, with a cutoff value<or=7, the DWI score could discriminate the deteriorated group from the non-deteriorated group with a sensitivity of 50% and specificity of 87.5%, whereas for ASPECTS, sensitivity was 50% and specificity, 81.2%. The DWI score, ASPECTS, and DWI volume had no correlation with NIHSS score but weak negative correlations with the DWI volume (P<0.01; Spearman's test). Comparing initial NIHSS score with each DWI score and DWI volume, the non-deteriorated group tended to have higher DWI scores and smaller DWI volumes than the deteriorated group, but there was no statistical difference between initial NIHSS and DWI scores. Though the DWI score was not statistically different, the threshold would be set to 6 points or above. Comparing initial DWI score with volume, patients with low DWI scores tended to show large variation in DWI volume and patients with small DWI volume showed large variation in DWI scores. There was no relation between hemorrhagic change and symptoms in either group. The semiquantitative DWI score easily evaluated extent of acute ischemic lesion on DWI and might be used to predict patient outcome after thrombolytic therapy more accurately than ASPECTS or DWI volume.


Bilateral pallidal stimulation for dropped head syndrome in tardive dystonia

遅発性ジストニアにおけるdropped head syndromeに対する両側淡蒼球深部脳刺激術


Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia

Tardive dystonia is a disabling movement disorder as a consequence of exposure to neuroleptic drugs. We followed 6 patients with medically refractory tardive dystonia treated by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for 21 +/- 18 months. At last follow-up, the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score improved by 86% +/- 14%, and the BFMDRS disability score improved by 80% +/- 12%. Bilateral GPi-DBS is a beneficial therapeutic option for the long-term relief of tardive dystonia.


進行性に巨大なvarixを形成した上錐体静脈洞部硬膜動静脈瘻の1例

進行性に巨大なvarixを形成した上錐体静脈洞部硬膜動静脈瘻の1例

We report a 61-year-old Japanease man with a superior petrosal sinus dural arteriovenous fistula (AVF) with a rapidly growing varix presenting as intracranial hemorrhage. He complained of headache and cerebellar ataxia. A computed tomography (CT) study revealed a huge high-density mass in the left cerebellar hemisphere. The mass had not been detected on a CT scan obtained elsewhere a month earlier. Magnetic resonance imaging revealed a huge flow void in the left cerebellopontine angle, and angiography showed a dural AVF located adjacent to the left superior petrosal sinus. It was supplied by the external carotid arteries and drained via the vein of Galen and a huge varix. After preoperative NBCA embolization of the feeding vessels, he underwent direct surgical ligation of the draining vein. However, as the size of the varix did not decrease and he developed brainstem symptoms, we excised the thrombosed varix. Ours is very rare case of superior petrosal sinus dural AVF resulting in consciousness disturbance due to brainstem compression by a huge varix. We postulate that the development of an intrathrombotic vascular channel and repeated recanalization may have been important factors in the rapid growth of the huge varix.


髄膜腫摘出の工夫 大孔部髄膜腫の手術

髄膜腫摘出の工夫 大孔部髄膜腫の手術


Ischemic Findings of T2*-Weighted 3-Tesla MRI in Acute Stroke Patients.

We compared ischemic findings on gradient echo-type T(2)*-weighted images at 3-tesla MRI (T(2)*WI) in patients with acute ischemia and major vessel occlusion, and stroke patients with lacunar infarction or branch atheromatous disease. Our study population consisted of 45 patients with acute stroke. They underwent 3-tesla MRI within 12 h of stroke onset. Included were 24 patients (13 men and 11 women, mean age 68 years) with major vessel occlusion and 21 patients (11 men and 10 women, mean age 69 years) with minor infarction such as lacunar infarcts or branch atheromatous disease. We classified vascular ischemic findings of T(2)*WI into 3 sign categories, i.e. artery susceptibility sign, cortical vessel sign (hypointensity and enlargement of the cortical vessels) and brush sign (hypointensity of vessels in the deep white matter). Decreased intensity in the ischemic parenchyma was designated ischemic tissue sign. We compared regions of interest in the hypoperfused area on flow-sensitive alternating inversion recovery (FAIR) images with our vascular ischemic findings. None of the vascular ischemic signs nor the ischemic tissue sign were found in patients with minor vessel disease. All 24 patients with major vessel occlusion manifested the cortical vessel sign, 23 the brush sign. The area with ischemic vessel signs on T(2)*WI was almost as large or somewhat smaller than the hypoperfused area on FAIR images. Compared to the contralateral side, 14 of 24 patients (58.3%) with major vessel occlusion showed decreased intensity in the ischemic parenchyma (ischemic tissue sign). Region of interest measurements on FAIR images demonstrated greater hypoperfusion in the area classified as ischemic tissue sign on T(2)*WI. Ischemic vessel signs and the ischemic tissue sign on T(2)*WI at 3 T would be useful to evaluate the extensive ischemia due to major vessel occlusion and may be correlated with the blood-oxygen-level-dependent effect due to increased deoxyhemoglobin. The ischemic tissue sign may be reflective of severe ischemia.


Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by a childhood onset of fixed dystonic posture with a dramatic and sustained response to relatively low doses of levodopa. DRD is thought to result from striatal dopamine deficiency due to a reduced synthesis and activity of tyrosine hydroxylase (TH), the synthetic enzyme for dopamine. The mechanisms underlying the genesis of dystonia in DRD present a challenge to models of basal ganglia movement control, given that striatal dopamine deficiency is the hallmark of Parkinson's disease. We report here behavioral and anatomical observations on a transgenic mouse model for DRD in which the gene for 6-pyruvoyl-tetrahydropterin synthase is targeted to render selective dysfunction of TH synthesis in the striatum. Mutant mice exhibited motor deficits phenotypically resembling symptoms of human DRD and manifested a major depletion of TH labeling in the striatum, with a marked posterior-to-anterior gradient resulting in near total loss caudally. Strikingly, within the regions of remaining TH staining in the striatum, there was a greater loss of TH labeling in striosomes than in the surrounding matrix. The predominant loss of TH expression in striosomes occurred during the early postnatal period, when motor symptoms first appeared. We suggest that the differential striosome-matrix pattern of dopamine loss could be a key to identifying the mechanisms underlying the genesis of dystonia in DRD.

Proceedings of the National Academy of Sciences of the United States of America


Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients

Proinflammatory and anti-inflammatory cytokines may play a pivotal role in cerebral inflammation, which is implicated in the development of brain injury. Systemic cytokine release is mediated by the sympathetic nervous system and catecholamines. The aim of this study was to investigate which parameters, among plasma levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha) and the levels of the catecholamines, epinephrine and norepinephrine, contribute to the clinical outcome in acute stroke patients. Thirty-seven acute stroke patients (ischemic, n = 19; hemorrhagic, n = 18) were enrolled. All of them were admitted to our hospital within 8 h after stroke onset. Neurological status was evaluated by a modified National Institute of Health Stroke Scale (mNIHSS) on admission and by a modified Rankin Scale (mRS) at 1 month. An mRS score of 3 or more at 1 month was considered to indicate poor outcome. Serum samples for the cytokine and catecholamine measurements were collected on admission. Plasma levels of IL-1beta, IL-6, IL-10, and TNF-alpha were determined by an enzyme-linked immunosorbent assay (ELISA) method and epinephrine and norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC). In the ischemic stroke patients, poor outcome was noted in 9 (47%). There were no significant differences in cytokine or catecholamine concentrations between patients with poor and good outcomes, and there was no association between clinical outcome and cytokine and catecholamine concentrations. In the hemorrhagic stroke patients, poor outcome was noted in 10 (56%). IL-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). In ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.


輸血拒否患者の髄膜腫手術

輸血拒否患者の髄膜腫手術


Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia: in-vivo and in-vitro studies

Angiotensin II type 1 (AT1) receptor blockers decrease ischemia by mechanisms dependent on and independent of arterial blood pressure in hypertensive rats and AT1-R knockout mice, respectively. However, the detailed mechanisms underlying the effects of AT1 receptor blockers remain unclear. To elucidate the systemic and focal effects of AT1 receptor blockers against cerebral ischemia in in-vivo and in-vitro studies. Normotensive Wistar rats were treated for 2 weeks with 0.5 or 1 mg/kg candesartan cilexetil and then subjected to 2-h middle cerebral artery occlusion-reperfusion. Human umbilical endothelial cells were stimulated with the active form of candesartan and angiotensin II in the absence and presence of an angiotensin II type 2 (AT2) receptor antagonist. In candesartan-pretreated hypotensive and nonhypotensive rats, blood pressure was moderately increased during middle cerebral artery occlusion and fell gradually to the baseline after the reperfusion; it remained elevated in the control even after the reperfusion occlusion. Candesartan treatment resulted in a decrease in the cortical infarct volume and oxidative damage, the hypoxic status was improved, and the expression of repair-associated and growth-associated proteins in the cortical penumbra was augmented. Candesartan also increased the eNOS mRNA level and the lumen size of the middle cerebral artery. In human umbilical endothelial cells, candesartan increased the eNOS protein level AT2-R dependently, inhibited the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and angiotensin II-induced intracellular reactive oxygen species and nitric oxide, and promoted the extracellular release of nitric oxide, suggesting that it augmented the bioavailability of nitric oxide. Among the mechanisms candesartan exerts in its protection against cerebral ischemia, restoration of endothelial function may represent an attractive therapeutic goal to address cerebral ischemia.


REIC/Dkk-3 induces cell death in human malignant glioma

The progression of glioma to more malignant phenotypes results from the stepwise accumulation of genetic alterations and the consequent disruption of the apoptotic pathway and augmentation of survival signaling. REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of the growth of several human cancers; however, to date it has not been identified in brain tumors. We compared the gene and protein expression of REIC/Dkk-3 in human malignant glioma and normal brain tissues using quantitative real-time PCR, Western blotting, and immunohistochemistry. We also performed small interfering REIC/Dkk-3 (siREIC/Dkk-3) knockdown and REIC/Dkk-3 overexpression experiments to examine the role of REIC/Dkk-3 in human malignant glioma cells in vitro. In brain tissue from patients with malignant glioma, the gene and protein expression of REIC/Dkk-3 was lower than in normal brain tissue and was related to the malignancy grade. In the primary glioblastoma cell line, REIC/Dkk-3 transfection led to apoptosis owing to the activation of phosphorylated JUN, caspase-9, and caspase-3 and the reduction of beta-catenin; in REIC/Dkk-3 knockdown experiments, cell growth was augmented. Our results suggest that REIC/Dkk-3 regulates the growth and survival of these cells in a caspase-dependent and -independent way via modification of the Wnt signaling pathway. Our work is the first documentation that the gene and protein expression of REIC/Dkk-3 is down-regulated in human malignant glioma. Our demonstration of the mechanisms underlying REIC/Dkk-3-induced cell death indicates that REIC/Dkk-3 plays a pivotal role in the biology of human malignant glioma and suggests that REIC/Dkk-3 is a promising candidate for molecular target therapy.


もやもや病疑診例の母親から生まれたもやもや病確診例の姉妹の1家系

もやもや病疑診例の母親から生まれたもやもや病確診例の姉妹の1家系


Thalamic Vo-complex vs pallidal deep brain stimulation for focal hand dystonia


Choreoathetosis due to rupture of a distal accessory anterior cerebral artery aneurysm


破裂脳動脈瘤に対するコイル塞栓術後の髄液ドレナージは血管攣縮を減少させるか?

破裂脳動脈瘤に対するコイル塞栓術後の髄液ドレナージは血管攣縮を減少させるか?


摘出困難な内側型蝶形骨縁髄膜腫

摘出困難な内側型蝶形骨縁髄膜腫


髄膜腫摘出の工夫 大きな内側型蝶形骨縁髄膜腫

髄膜腫摘出の工夫 大きな内側型蝶形骨縁髄膜腫


大型内頸動脈瘤における，内頸動脈遮断試験の方法と実際内頸動脈瘤—脳血管内治療の立場からー

第15回脳血管内治療仙台セミナー講演集

第15回脳血管内治療仙台セミナー講演集


Diagnosis and Treatment in Stroke Center of Tokushima University Hospital : Efficacy of 3 Tesla Stroke MRI(<Topic> Stroke Care Unit, Stroke Center)

徳島大学病院stroke centerでの脳卒中医療の現状 -特にstroke MRIの有用性-

After the stroke care unit of Tokushima University hospital was established in November 1999, stroke MRI (diffusion-, perfusion-weighted image, MRA) was performed to initially evaluate stroke patients, except for SAH. Since April 2004, 3 tesla MRI has been used for stroke MRI, and T2^* weighted image was added to routine study of stroke MRI. 3 tesla stroke MRI can reduce examination time and also take functional MR images, which yield important information for diagnosis and treatment decisions. The combination of our stroke center and rehabilitation hospital is a key factor in improving patients' outcomes for acute rehabilitation and improving quality of life.


Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis inn relation to oxidized low-density lipoprotein and plaque vulnerability

Although carotid endarterectomy (CEA), the gold standard in stroke prevention, has been performed in the late stage after the insult, its optimal timing remains unclear. Using biomarkers in plaque and plasma, we evaluated oxidative stress and plaque vulnerability between early and late CEA in symptomatic patients. We compared symptomatic stroke patients who underwent early CEA within 4 weeks of the last insult (group A; n = 15) with those who received CEA in the late stage beyond 4 weeks from the last symptom (group B; n = 57). They were divided into vulnerable (group Av, n = 13; group Bv, n = 33) and stable (group As, n = 2; group Bs, n = 24) subgroups according to the pathologic findings on their plaques. We studied the relationships among their primary symptoms, clinical findings, oxidized low-density lipoprotein levels, and gelatinase A (matrix metalloproteinase [MMP]-9) activity in their plaques and plasma. Group A had a variety of symptoms; there was no difference in the outcome of CEA between groups A and B. The plaque and plasma oxidized low-density lipoprotein levels were higher in group A than in group B (P < .05). The incidence of pathologically vulnerable plaque was higher in group A than in group B. Plaque oxidized low-density lipoprotein levels and MMP-9 activity were similar in group Av and group Bv and were higher in those groups than in group As and Bs. We first demonstrated that vulnerable plaques in patients subjected to early CEA manifested a remarkable increase in oxidized low-density lipoprotein and MMP-9 activation. Our findings suggest that early CEA may be beneficial in the aspect of oxidative stress.


Diagnosis of acute stroke patients: using MRI as the first selected modality

MRIを第一選択とした急性期脳血管障害の画像診断法


AVM Operation with Preoperative Embolization

術前塞栓術を併用したAVM手術


Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats

Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague-Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery-olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohistochemically by using antibodies against endothelial nitric oxide synthase, alpha-smooth muscle actin, macrophages, and matrix metalloproteinase-9. Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.


Study on factors related to loss of lower extremity muscle mass in elderly acute stroke patients

The present study investigated the factors contributing to the loss of upper and lower extremity muscle mass in three elderly stroke patients with right hemiplegia in whom our rehabilitation program could not be performed at 1‐2 weeks after onset. The results revealed common factors such as prolonged accurate microinjection of hypotensive agents, severe hemiplegia(Brunnstrom stage I or Ⅱ), diarrhea and delayed initiation of tube feeding at 3 to 8 days after onset. With regard to individual differences, while all patients were recovering in bed, the degree of decrease in muscle mass varied among patients because they moved their extremities differently.

JNI : The Journal of Nursing Investigation


3 Tesla T2^*-weighted MRI demonstrating an intra-MCA embolus in a young adult with cerebral embolism

3 Tesla T2 *強調MRIで中大脳動脈内塞栓子を呈した若年性脳塞栓症の1例


Effects of intervention with back-lying exercises with bent knees pointing upwards to prevent disuse muscle atrophy in patients with post-stroke hemiplegia

The present study measured lower extremity muscle mass using DXA (Dual energy X-ray Absorptiometry) in order to verify the effectiveness of intervention with a series of movements, including lying hip raise exercise with bent knees pointing upwards, among bedridden patients with post-stroke hemiplegia in the acute post-stroke period. Subjects in the intervention group were required to perform 10 repetitions of a series of back-lying exercises once a day with researchers, in addition to the exercises performed by those in a control group. The first measurement of muscle mass was conducted at three to five days after onset, and the second measurement was conducted seven days after the first. Muscle mass in the lower extremities was reduced by approximately 600g (decrease rate : 9%)on the paralyzed side and by 280g on the non-paralyzed side(decrease rate: 5%)in one week in the Brunnstrom stage ≤ II subgroup(site of measurement : lower extremities) (n＝8) of the control group (n＝23). The decrease in muscle mass in the Brunnstrom stage ≤ II subgroup (n＝4) of the intervention group (n＝15) was approximately 260g on the paralyzed side (decrease rate : 5%) and approximately 280g (decrease rate : 5%)on the non-paralyzed side. Thus, muscle mass decreased on both sides, and this occurred regardless of degree of paralysis. Comparison of the Brunnstrom stage ≥ III subgroups between the control and intervention groups also confirmed that the decease in muscle mass was smaller in the latter group. Thus, it was confirmed that back-lying exercises combining lower extremity movements, including hip raises with bent knees pointing upwards, prevented the decrease in lower extremity muscle mass on the paralyzed side in post-stroke patients. The present study also suggests that these exercise movements can be applied to preventive care for bedridden patients with other severe diseases.


Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated primary intracranial chriocarcinoma: case report

We report a 17-year-old male with disseminated intracranial choriocarcinoma at the basal ganglia whose consciousness level was very low at diagnosis. He received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy prior to radical excision of the tumor. Postoperatively he was treated with three courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and etoposide (VP-16)) and peripheral blood stem-cell transplantation. This combination of therapies resulted in tumor regression on MRI and remarkable improvement in his neurological condition. Ours is the first report of the effectiveness of NAT followed by radical surgery in a patient with disseminated primary intracranial choriocarcinoma.


Hemodynamic cerebral ischemia during carotid endarterectomy evaluated by intraoperative monitoring and post-operative diffusion-weighted imaging

We used the result of monitoring to evaluate patients with post-operative neurological deficits attributable to hemodynamic cerebral ischemia owing to cross-clamping of the carotid artery. We evaluated 131 carotid endarterectomy (CEA) procedures performed on 118 patients, 96 men and 22 women ranging in age from 38 to 82 years (mean: 67.1 years). For monitoring, we used a combination of somatosensory evoked potential (SEP), functional dynamic electroencephalography (EEG), near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD). Patients who awoke with neurological deficits after CEA immediately underwent diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA). In 30 of the 131 procedures (22.9%), intraoperative monitoring disclosed abnormalities after cross-clamping of the internal carotid artery (ICA). In two of these 30 patients, shunt was not introduced, because of full recovery of monitoring after blood pressure increasing, however, one patient demonstrated transient ischemic attack (TIA). In six of remaining 28 patients who need shunt, transient hemodynamic cerebral ischemia occurred, however, all patients recovered gradually within 18 hours after CEA. No new lesions were detected on post-operative DWI of the seven patients and MRA demonstrated good patency of the carotid artery. The other 101 patients whose intraoperative monitoring after cross-clamping of the ICA did not disclose abnormalities demonstrated no hemodynamic TIA. Hemodynamic ischemia owing to cross-clamping of the ICA is rare in patients treated by CEA. However, in patients manifesting neurological deficits upon awakening from CEA, DWI and MRA should be performed immediately to facilitate their prompt treatment.


急性期および亜急性期CEAの妥当性について -酸化LDLを指標として- 脳梗塞急性期治療の最前線 -血栓溶解療法の新たな展開-


髄膜腫摘出の工夫 内側型蝶形骨縁髄膜腫

髄膜腫摘出の工夫 内側型蝶形骨縁髄膜腫


椎骨脳底動脈閉塞症に対する急性期血行再建術の適応と有効性 -Stroke MRIによる検討-


健常者に発症し治療に難渋したクリプトコッカス髄膜脳炎の1例

健常者に発症し治療に難渋したクリプトコッカス髄膜脳炎の1例


3T-MRIによるStroke MRIの現状と問題点 脳梗塞急性期治療の最前線ー血栓溶解療法の新たな展開ー


脳梗塞急性期血栓溶解療法に関する全国アンケート調査結果報告

脳梗塞急性期血栓溶解療法に関する全国アンケート調査結果報告

第22回日本脳神経血管内治療学会講演集

第22回日本脳神経血管内治療学会講演集


The usefulness and problem for MR I examination by using clinical 3T-MRI


Impact of bilateral pallidal stimulation on DYT1-generalized dystonia in Japanese patients

Early-onset generalized dystonia attributable to a DYT1 gene mutation is a hyperkinetic movement disorder that responds poorly to pharmacotherapy. In this video brief, we show that continuous bilateral stimulation of the globus pallidus internus produced sustained and marked improvements in the motor symptoms and functional disabilities of Japanese patients with DYT1-generalized dystonia.


Changes in lower extremity muscle mass among bedridden patients with post-stroke hemiplegia in the acute post-stroke period

The present study analyzed16patients who were bedridden for one week immediately after onset of post-stroke hemiplegia. We used DXA(dual energy X-ray absorptiometry)to determine changes in muscle mass in the lower extremities on both paralyzed and non-paralyzed sides. The first measurement was conducted 3 to 5 days after the onset, and the second measurement was conducted 7 days after the first. Muscle mass in the lower extremities was reduced by approximately 600g (9%) on the paralyzed side with and by 200g on the non-paralyzed side (3%) in the Brunnstrom stage≤II group (n＝5). Although the decrease of muscle mass in the Brunnstrom stage≥III group(n＝11, relatively slight degree of functional motion impairment)was not significant, a decrease of approximately 300g (decrease rate : 5%)was observed on the paralyzed side and approximately 100g (decrease rate : 1．5%)was seen on the non-paralyzed side. Hence, muscle mass declined on both sides, and this occurred regardless of degree of paralysis. The findings suggested that conventional range of motion exercises, functional position maintenance, and postural changes are inadequate to prevent disuse muscle atrophy in post-stroke patients ; thus, it is necessary to develop a new rehabilitation program which adopts different exercises such as trunk motion, even for patients in the acute stage after stoke onset.


Hemichorea due to hemodynamic ischemia associated with extracranial carotid artery stenosis. Report of two cases.

In this paper the authors describe two patients with recurrent hemiparesis and limb shaking that gradually progressed to hemichorea. Cerebral angiography confirmed severe unilateral internal carotid artery stenosis (95%) contralateral to the hemichorea. The cerebral blood flow, assessed using N-isopropyl-p-(iodine-123) iodoamphetamine single-photon emission computed tomography (SPECT), disclosed markedly decreased vascular reserves in both patients. After carotid endarterectomy was performed, the hemichorea gradually subsided and SPECT confirmed increased cerebral perfusion. The results in these cases indicate that surgical revascularization is effective for hemichorea due to cerebral ischemia with reduced vascular reserve.


Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome

To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n = 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively.

International Journal of Radiation Oncology*Biology*Physics


Microcatheter pull-up technique in the transvenous embolization of an isolated sinus dural arteriovenous fistula

The authors describe a novel technique involving the use of a gooseneck snare for microcatheterization of isolated sinus dural arteriovenous fistulas (DAVFs). In some patients the inferior petrosal and transverse-sigmoid sinuses, the route of transvenous embolization (TVE) for DAVF, are separated by several channels. Even if a guidewire can be passed over the occluded portion and the affected sinus can be accessed, one may not necessarily be able to insert a microcatheter. The authors report on three patients who underwent successful microcatheterization via a novel pull-up technique, which makes use of a gooseneck snare to perform TVE even in very difficult circumstances.


Strategy and Outcome in Patients with Unruptured Cerebral AVM(<Topics>Unruptured Arteriovenous Malformations)

未破裂脳動静脈奇形の治療方針とその成績

The treatment of unruptured cerebral arteriovenous malformation (AVM) is still controversial. We have been treating these patients according to the Spetzler & Martin (S&M) grading system. We retrospectively evaluated the outcomes of 46 unruptured AVM patients and also evaluated the bleeding rate during follow-up period. Recently we also started performing functional MRI, trac-tography, and 3-dimensional (3D) angiography for these patients before treatment. In 18 of 22 patients in S&M Grade I and II, AVMs were surgically removed and the outcome was good. Six of 9 patients in S&M Grade IV and V, were conservatively treated. In patients in S&M Grade III, various treatments were performed according to the location of the AVM, but all their outcomes were favorable. The rate of permanent surgical complications was 15.3% in 26 unruptured AVM patients. Based on our treatment results, aggressive treatment should be performed in patients with S&M Grade I and II. However, treatment decisions must be carefully considered based on functional MRI, tractography of AVM, and 3D angiography.


Alleviation of camptocormia by bilateral subthalamic nucleus stimulation in a patient with Parkinson's disease

Camptocormia, known also as "bent spine syndrome", is characterized by involuntary truncal flexion of the thoraco-lumbar spine that appears in the sitting or standing position. Although Parkinson's disease (PD) is the most frequent etiologic factor, this postural disorder responds poorly to levodopa or other medications. We report a PD patient in whom chronic bilateral subthalamic nucleus stimulation produced a striking alleviation of camptocormia.


Psychiatric symptoms and subthalamic nucleus stimulation in Parkinson's disease. A retrospective study in our Japanese patients

Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty-five patients underwent bilateral STN stimulation. Pre- and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab-England (S-E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug-induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients' psychiatric symptoms. Postoperative S-E score showed a significant improvement compared to the pretreatment baseline in both of "on" and "off" medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S-E score in "on" state (p < 0.01). Preoperative score for intellectual impairment was only a significant predictor of worse postoperative ADL in "off" state. Conclusions. The markedly lower dose of levodopa may suggest ethnic characteristics of our Japanese patients with respect to tolerance for antiparkinsonian medications. Preoperative manifestation of drug-induced psychosis and cognitive dysfunction were the major factor that strikingly suppressed daily activities after STN stimulation.


海綿静脈洞部硬膜動静脈瘻の経時的変化

海綿静脈洞部硬膜動静脈瘻の経時的変化


Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II --- experimental study of the effect of hormone replacement therapy in rats

The increased incidence of cerebral aneurysms in postmenopausal women appears to be related to low levels of circulating estrogen. Using a rat model of aneurysm induction, the authors found that oophorectomy increased the incidence of experimental cerebral aneurysms (Part I in this issue). In the current study they examined the effects of hormone replacement therapy (HRT) on the formation of cerebral aneurysms in rats. Forty-five female Sprague-Dawley rats were divided into three equal groups. The animals in Groups A and B were subjected to a cerebral aneurysm induction procedure (renal hypertension and right common carotid artery ligation) followed 1 month later by bilateral oophorectomy. After an additional week the rats in Group A received 17beta estradiol continuous-release pellets. The rats in Group C served as controls. Three months after the aneurysm induction procedure, all the rats were killed and vascular corrosion casts of their cerebral arteries were prepared and checked for aneurysmal changes. Using a scanning electron microscope, the authors recorded aneurysmal changes as endothelial changes alone (Stage I), endothelial changes with intimal pad elevation (Stage II), and saccular aneurysm formation (Stage III). Aneurysmal changes (Stages I, II, and III) occurred in one third of rats that had undergone oophorectomy and were receiving HRT (Group A), compared with 87% of the rats that had undergone oophorectomy but did not receive HRT (Group B). Although most of the aneurysmal changes identified in Group A rats were limited to Stage I or II, most changes in Group B animals were identified as saccular dilation (Stage III). The findings demonstrated the significant protective role of estrogen against the formation and progression of cerebral aneurysms. It appears to be related to the beneficial effects of estrogen on the function and growth of endothelial cells, which play a major role in preserving the integrity of the vascular wall.


Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part I --- experimental study of the effect of oophorectomy in rats

Estrogen has been shown to play a central role in vascular biology. Although it may exert beneficial vascular effects, its role in the pathogenesis of cerebral aneurysms remains to be determined. To elucidate the role of hormones further, the authors examined the effects of bilateral oophorectomy on the formation and progression of cerebral aneurysms in rats. Forty-five female, 7-week-old Sprague-Dawley rats were divided into three equal groups. Group I consisted of intact rats (controls). To induce cerebral aneurysms, the animals in Groups II and III were subjected to ligation of the right common carotid and bilateral posterior renal arteries. One month later, the rats in Group II underwent bilateral oophorectomy. Three months after the experiment began all animals were killed and cerebral vascular corrosion casts were prepared and screened for cerebral aneurysms by using a scanning electron microscope. Plasma was used to determine the level of estradiol and the gelatinase activity. Hypertension developed in all rats except those in the control group. The estradiol level was significantly lower in Group II than in the other groups (p < 0.01). The incidence of cerebral aneurysm formation in Group II (60%) was three times higher than that in Group III (20%), and the mean size of aneurysms in Group II (76 +/- 27 microm, mean +/-standard deviation) was larger than that in Group III (28 +/- 4.6 microm) (p < 0.05). No aneurysm developed in control animals (Group I), and there was no significant difference in plasma gelatinase activity among the three groups. The cerebral aneurysm model was highly reproducible in rats. Bilateral oophorectomy increased the susceptibility of rats to aneurysm formation, indicating that hormones play a role in the pathogenesis of cerebral aneurysms.


Evaluation of Aneurysm Stability After Endovascular Embolization With Guglielmi Detachable Coils --- Correlation Between Long-Term Stability and Volume Embolization Ratio

The correlation between volume embolization ratio (VER), the percentage of aneurysm volume occupied by coils, and aneurysm stability after endovascular treatment with platinum coils was studied in 86 patients who underwent embolization of 88 cerebral saccular aneurysms with standard platinum coils between March 1997 and January 2003. Radiographic follow up was possible of 62 aneurysms with greater than 70% obliteration on immediate post-procedure angiograms for more than 6 months. Immediate post-procedure evaluation found that 12 of 14 small (<4 mm), 12 of 38 medium (4-<10 mm), and two of 10 large (> or =10 mm) aneurysms had high (> or =25%) VER. In addition, the VER was high in 22 of 40 aneurysms with small (<4 mm) and four of 22 with wide necks (> or =4 mm). Evaluation of 57 aneurysms at 6 months after coil embolization found recanalization in two of 25 aneurysms with high VER and 21 of 32 with low (<25%) VER, indicating that aneurysms with high VER are significantly more stable than those with low VER (p < 0.01). VER strongly affects aneurysm stability, so high VER is desirable and a useful predictor of aneurysm stability.


Anaplastic ganglioglioma of cerebellopontine angle: A case report and review of literatures

A 64-year-old woman presented with a rare anaplastic ganglioglioma in the right cerebellopontine angle manifesting as dizziness persisting for 2 weeks. Preoperative magnetic resonance (MR) imaging revealed a partially enhanced cystic lesion of the right cerebellopontine angle. The tumor was subtotally removed through a right lateral suboccipital craniectomy. The tumor was thought to originate from the brain stem with exophytic growth into the right cerebellopontine angle. Histological examination showed neoplastic ganglional and glial cells with anaplastic features such as mitosis, pleomorphism, and endothelial proliferation. The MIB-1 labeling index of the glial components was 40% to 60%. The diagnosis was anaplastic ganglioglioma (World Health Organization grade IV). She received postoperative radiotherapy but died of respiratory failure with tumor recurrence 11 months after the operation. Gangliogliomas usually have a good prognosis. Histological features of anaplasia and a high MIB-1 labeling index may be predictive of a poor clinical outcome.


Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction

We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups: GI (n = 24) had cortical lesions, and GII (n = 27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n = 13; GIIa, n = 14) and its efficacy was studied by comparing their plasma OxLDL, S-100B, and MnSOD levels to those in patients without edaravone (GIb, n = 11, GIIb, n = 13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa than GIb patients (0.177 +/- 0.024 ng/microg apoB vs 0.219 +/- 0.026, P < 0.05). In GIIa patients, pre- and posttreatment plasma OxLDL was not significantly different (0.156 +/- 0.013 vs 0.152 +/- 0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (P < 0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb patients. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.


Contribution of an imbalance between oxidant-antioxidant systems to plaque vulnerability in patients with carotid artery stenosis

Reactive species of oxygen and nitrogen mediate the oxidative modification of low-density lipoprotein (LDL). Oxidation of LDL is inhibited by endogenous radical scavenging enzymes such as manganese superoxide dismutase (SOD) and Cu-ZnSOD that catalyze dismutation of oxygen to H2O2. Low-molecular antioxidants such as uric acid regulate the inactivation that appears to be linked to an increase in peroxynitrite resulting in oxidized LDL (OxLDL) elevation. The authors evaluated whether a focal imbalance between pro- and antioxidant systems induces plaque vulnerability in patients with carotid artery (CA) stenosis. Carotid artery plaques obtained in 35 patients who had undergone carotid endarterectomy were classified as vulnerable or stable based on histopathological findings. In vulnerable plaques, OxLDL, measured using enzyme-linked immunosorbent assay, was significantly higher (p < 0.01) and SOD activity significantly lower than in stable plaques (p < 0.05). The plaque and plasma OxLDL levels were inversely correlated with plaque SOD activity (p < 0.01). The physiological uric acid level in all plaques was one fourth to one eighth of that in plasma and appeared to be unable to protect Cu-ZnSOD from degradation by H2O2. Immunohistochemical analysis showed increased peroxynitrite and OxLDL in vulnerable plaques. There was a significant correlation between plaque and plasma OxLDL levels (p < 0.01). Analysis of the results suggests that a focal imbalance between pro- and antioxidant defense systems in patients with CA plaques induces an increase in plaque OxLDL levels and consequent plaque instability, contributing to high levels of plasma OxLDL.


痴呆症状で発症し治療に難渋したテント部硬膜動静脈瘻の2例

痴呆症状で発症し治療に難渋したテント部硬膜動静脈瘻の2例


Rescue Revascularization Therapy With a Stent-in-Stent Technique for Acute Intracranial Internal Carotid Artery Occlusion --- Case Report

A 45-year-old woman presented with progressive stroke due to occlusion of the left internal carotid artery at the level of the cavernous portion (C3/C4). Revascularization was achieved by stent deployment following percutaneous transluminal angioplasty. Stent thrombosis occurred 7 days after primary stenting; it was successfully treated with the stent-in-stent technique. The patient was able to return to her independent life with no sequelae except for slight hemiparesis. In combination with appropriate antiplatelet treatment, the stent-in-stent technique should be considered as a rescue option in patients with re-occlusion of an intracranial stent.


Vascular corrosion casts mirroring early morphological changes that lead to the formation of saccular cerebral aneurysm: an experimental study in rats

The formation of cerebral aneurysms involves complex processes and little is known about the mechanisms by which they originate, grow, and rupture. The purpose of this study was to identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysms. Twenty male Sprague-Dawley rats were subjected to cerebral aneurysm induction (renal hypertension and right common carotid artery ligation); 10 intact rats served as the control group. The animals were killed after 2 months, and a vascular corrosion cast of their cerebral arteries was prepared and screened for aneurysm development by using a scanning electron microscope. Sequential morphological changes observed at the cerebral artery bifurcation in response to hemodynamic shear stress included endothelial changes, intimal pad elevation, and saccular dilation. Endothelial cell changes were the first observed morphological changes; they were followed by various degrees of artery wall dilation. No aneurysmal changes developed in any of the control rats. Of the 20 surgically treated rats, 11 displayed aneurysmal changes. In five of these animals only changes in the endothelial cell imprints could be identified. In the other six rats morphological changes in endothelial cells were associated with different stages of aneurysmal dilation. This is the first study to demonstrate in vivo early morphological changes that lead to the formation of cerebral aneurysms. The morphological findings indicate the principal role of endothelial cells in the pathogenesis of cerebral aneurysms and suggest that hemodynamic shear stress and blood flow patterns may precipitate these early changes.


Angiographic Changes in Venous Drainage of Cavernous Sinus Dural Arteriovenous Fistulae after Palliative Transarterial Embolization or Observational Management --- A Proposed Stage Classification

We assessed whether angiographic changes in venous drainage patterns occur over time in cavernous sinus dural arteriovenous fistulae (dAVFs) without a complete cure. We classified 65 cavernous sinus dAVFs into three types on the basis of initial angiographic findings. In Type 1, both anterior and posterior drainage routes were open; in Type 2, the posterior drainage route was closed, whereas the anterior drainage route was open; and in Type 3, both the posterior and anterior drainage routes were closed. Of the 65 dAVFs, 40 were of Type 1, 21 of Type 2, and 4 of Type 3. During the follow-up period, 17 of the dAVFs that were treated palliatively with transarterial embolization (n = 11) or monitored without therapy (n = 6) demonstrated angiographic changes. In these 11 patients, there was a change in the venous drainage pattern from Type 1 to Type 2 (n = 5), from Type 2 to Type 3 (n = 3), and from Type 1 to Type 3 (n = 3). One of 11 had a conversion into a lesion with cortical venous drainage. The remaining 6 dAVFs (4 with observational management, 2 with transarterial embolization) demonstrated closure of the fistula; in 5 of these, the affected cavernous sinus was not depicted on follow-up angiograms. In some cavernous sinus dAVFs with palliative transarterial embolization or observational management, there was a change in the venous drainage patterns, consisting of a decrease in the number of venous drainage routes. There was a trend for the posterior route to close before the anterior drainage or cortical drainage route. This suggests the occurrence of a staged progression in a regular direction in cavernous sinus dAVFs. Without treatment aiming at a complete cure, most cavernous sinus dAVFs can behave benignly, with a low possibility of development of cortical venous reflux during follow-up.


Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement

Oxidized low-density lipoprotein (OxLDL) plays a major role in atherosclerosis. We undertook the present study to clarify the relationship between plasma OxLDL and the ischemic volume. We used ELISA to determine plasma OxLDL levels, and performed diffusion- and perfusion-weighted MRI (DWI, PWI) to measure the ischemic volume in 44 ischemic stroke patients. Based on the location of the ischemic lesion, they were divided into three groups: Group I (GI, n = 21) had cortical lesions, Group II (GII, n = 17) had lesions in the basal ganglia or brain stem, and Group III (GIII, n = 6) had massive lesions that involved one entire hemisphere. In GI, but not GII and GIII, plasma OxLDL was significantly higher than in 19 age-matched controls (p < 0.01) and was significantly correlated with the initial ischemic volume visualized on DWI (p = 0.01), PWI (p < 0.01), and the DWI-PWI mismatch (p < 0.05). A persistent increase in plasma OxLDL was associated with enlargement of the ischemic lesion in the early phase after the insult. These findings suggest that elevated plasma OxLDL levels are associated with moderate ischemic damage in patients with cortical lesions (GI), but not those with massive hemispheric lesions (GIII), which may be irreversible. In addition, elevated plasma OxLDL may represent a predictor of enlargement of the ischemic lesion.


Multiple cystic cavernous angiomas associated with hemorrhage

A 29-year-old man presented with impaired mental concentration and inability to remember. Magnetic resonance and computed tomography studies revealed multiple calcified cysts. Craniotomy was performed and one of the lesions was resected. The histological diagnosis was cavernous angioma. The first report of multiple cystic cavernous angiomas is reported.


脳腫瘍の診断と治療 -最新の研究動向- VI. 脳腫瘍の治療 放射線療法 中性子捕捉療法 -現状と問題点-

Nihon Rinsho. Japanese Journal of Clinical Medicine


近位部閉塞後，瘤増大をきたした出血性解離性椎骨動脈瘤の1例，頭蓋内動脈解離と脳血管内治療

第12回脳血管内治療仙台セミナー講演集

第12回脳血管内治療仙台セミナー講演集


Hereditary Hemorrhagic Telangiectasia and its Animal Model

遺伝性出血性毛細血管拡張症と動物モデル(第24回日本脳神経外科コングレス「脳動静脈奇形の基礎と臨床」発表演題)

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant vascular dysplasia characterized by dilated vessels and arteriovenous malformations (AVMs). Five to 10% of cerebral AVMs observed in general population are associated with this disease. Two genes, endoglin and activin receptor-like kinase 1, are associated with HHT. To understand the etiology of this disorder, we evaluated the cerebral vasculature of endoglin heterozygous (Eng^<+/->) mice using vascular corrosion cast technique. Eng^<+/-> mice showed significant structural alterations in cerebral blood vessels, indicating that the level of endoglin on endothelium is critical for maintenance of normal vasculature. In this article, we would give an outline of current concepts of HHT and introduce the data obtained from its animal models.

遺伝性出血性毛細血管拡張症(hereditary hemorrhagic telangiectasia ; HHT)は,血管形成異常から鼻出血・毛細血管拡張・AVMを引き起こす常染色体優性遺伝疾患である.その責任遺伝子としてendoglin, activin receptor-like kinase 1の2つが同定されている.近年,HHTの動物モデルとしてendoglinヘテロ接合体(Eng^<+/->)マウスを用いた研究が報告されるようになり, endoglinの血管形成における役割が次第に解明されるようになってきた.今後,基礎・臨床の両面から解析が進むことにより,現時点では不明なHHT患者における重症度・発現時期のheterogeneityのみならず,脳動静脈奇形発生のメカニズムの解明が期待される.


Radiation injury of boron neutron capture therapy using mixed epithermal- and themal neutron beams in patients with malignant glioma

The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n = 8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n = 4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n = 6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4+/-4.2 Gy, 15.7+/-1.2 and 13.9+/-3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8+/-1.3 Gy in positive and was 12.6+/-4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8+/-3.8 Gy in positive and was 13.6+/-4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor exists in speech center.


Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction.

Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction.


Detection of Enlarged Cortical Vein by Magnetic Resonance Imaging Contributes to Early Diagnosis and Better Outcome for Patients With Anterior Cranial Fossa Dural Arteriovenous Fistula

Twelve patients (10 men, 2 women) with anterior cranial fossa dural arteriovenous fistula (AVF) were treated at our institute between January 1976 and March 2002. Intracranial hemorrhage was the presenting symptom in six patients. Magnetic resonance (MR) imaging findings identified abnormal cortical veins as flow voids in four of five patients. Angiography was the basis of the diagnosis in all patients. Surgery was the primary treatment in nine patients. The other three patients refused intervention and managed conservatively. Surgical morbidity was negligible and the treatment outcome was highly dependent on the clinical status at presentation. In contrast to the reported high incidence of intracranial hemorrhage in patients with dural AVF in the anterior cranial fossa, only half of our study population presented with hemorrhage. Enlarged cortical veins in the frontobasal area could be detected as flow voids on MR images. This finding contributed to the early diagnosis and treatment of patients treated at our institution for dural AVF in the anterior cranial fossa, and to the better outcomes we obtained in these patients.


Ruptured de novo thrombotic giant aneurysm induced by ethyl 2-cyanoacrylate --- Case report

A very rare case of a ruptured aneurysm induced by ethyl 2-cyanoacrylate is reported. Six years earlier, this 68-year-old woman had undergone microvascular decompression for trigeminal neuralgia during which the left vertebral artery, which compressed the exit zone of the trigeminal nerve, had been detached and fixed to the dura mater of the petrous bone with ethyl 2-cyanoacrylate. Shortly thereafter she underwent microvascular decompression for left-side facial palsy; again ethyl 2-cyanoacrylate was used. Six years later, she suffered a subarachnoid hemorrhage because of rupture of a new aneurysm of the left vertebral artery. She was referred to our hospital where coil embolization was attempted on the day following the insult. However, the left vertebral artery and the aneurysm could not be occluded completely, and she suddenly died 20 days later from rerupture of the aneurysm. This is the first pathologic report of a ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate. We suggest that arterial wall damage by ethyl 2-cyanoacrylate may have contributed to the development of the de novo aneurysm.


Ruptured aneurysm arising from a basilar artery fenestration and associated with a persistent primitive hypoglossal artery --- Case report and review of the literature

A 42-year-old woman experienced the sudden onset of a severe headache. Angiograms demonstrated a persistent primitive hypoglossal artery (PHA) originating from the internal carotid artery at the C-2 vertebral level. In addition, a fenestration at the PHA-basilar artery (BA) junction and an aneurysm at the proximal end of this fenestration were revealed. To perform endovascular embolization of the aneurysm, a microcatheter was introduced into the aneurysm sac via the PHA and two Guglielmi Detachable Coils were placed in the aneurysm. The patient's postoperative course was uneventful, and she was able to resume her normal life. Although many clinical cases have been reported in which a ruptured aneurysm was associated with a PHA or a BA fenestration, as far as the authors know there has been no case in the literature in which a ruptured aneurysm associated with both anomalies and no case in which endovascular embolization was used to treat a ruptured aneurysm associated with a PHA. This rare case is discussed and a review of the relevant literature is presented.


Development of real-time intra-operative analysis software for brain activity using measured EEG

術中脳活動リアルタイム解析ソフトウェアの開発

頸動脈内膜剥離術等のある種の手術では脳への血流を一時的に遮断する必要がある場合がある．このような場合脳の状態のリアルタイムモニタリングは安全性確保のためにを重要な役割を担っている．本研究では計測した脳波から波形表示，周波数解析，DRT(変化率2次元脳電図)表示，警告音の発生などを行うシステムをPC上で構築した．また新たな脳波解析手法として移動平均型ニューラルネットワークを用いた方法を提案し，臨床データを用いて解析を行った．

Transactions of the Japanese Society for Medical and Biological Engineering


Primitive Vertebrobasilar System Associated with a Ruptured Aneurysm

Persistent primitive lateral vertebrobasilar (PPLVB) anastomosis is a rare remnant of early fetal development whose occurrence, to our knowledge, has been reported only once. We now report a new variant in which the basilar artery was fed primarily by a PPLVB anastomosis because on one side the vertebrobasilar junction was incompletely developed and on the other it was aplastic. Aneurysmal rupture in this case may be attributable to excessive hemodynamic stress.


Histopathological findings in autopsied glioblastoma patients treated by mixed neutron beam BNCT

Since 1998, we have introduced a mixed epithermal- and thermal neutron beam for boron neutron capture therapy (BNCT) to improve the neutron beam distribution. Sixteen patients with malignant glioma (glioblastoma, n = 14; anaplastic ependymoma, n = 1; PNET, n = 1) were treated by BNCT in Japan. Of these, 9 died; 3 due to cerebrospinal fluid (CSF) dissemination, 1 each of tumor invasion, meningitis, pneumonia, and unknown causes, and 2 patients died of local recurrence or radiation necrosis. The current postmortem study is comprised of 3 patients with glioblastoma who were treated with BNCT employing an epithermal neutron beam and sodium borocaptate (BSH: Na2B12H11SH). None of the patients manifested local regrowth at the primary site. However, in 2 patients there was CSF dissemination; tumor cells were recognized throughout the subarachnoid space. In the other patient, tumor cells had massively invaded the ipsilateral- and contralateral hemisphere and brain stem from the bottom of the tumor cavity via the corpus callosum and cerebral peduncle. Our findings indicate that BNCT can achieve local control of glioblastoma at the primary site. However, to further improve the clinical outcome after BNCT, steps must be taken to prevent CSF dissemination.


Identification and characterization of Noc2 as a potential Rab3B effector protein in epithelial cells

The Rab3 family small G proteins (Rab3A-D) are involved in the regulated secretory pathway of brain and secretory tissues. Among Rab3-interacting proteins, Rabphilin-3, Rim, and Noc2, all of which contain a conserved Rab3-binding domain (RBD3), are generally recognized Rab3 effector proteins in neurons and secretory cells. Although Rab3B was also detected in epithelial cells, its function remained unknown. We isolated cDNA sequences from human epithelial Caco2-cell mRNA by degenerate RT-PCR based on the conserved amino acid sequence of RBD3. Multiple cDNA clones were identified as encoding Noc2. Northern blot analysis revealed that Noc2 mRNA was expressed not only in secretory tissues but also in epithelial tissues and cell lines. A pull-down assay demonstrated that Noc2 bound to Rab3B in a GTP-dependent manner. When Noc2 was co-expressed with the GTP-bound form of Rab3B, it was recruited from the cytosol to perinuclear membranes. Furthermore, overexpression of Noc2 inhibited the cell-surface transport of basolateral vesicular stomatitis virus glycoprotein. These results suggest that Noc2 functions as a potential Rab3B effector protein in epithelial cells.

Biochemical and Biophysical Research Communications


Ischemic basilar artery dissecting aneurysm treated by stenting only case report-

A 45-year-old man presented with enlargement of basilar artery dissecting aneurysm 10 months after suffering brain stem infarction. Combined stenting and placement of Guglielmi detachable coils (GDCs) was planned to obliterate the aneurysm sac. Stent deployment was performed but the procedure was halted to avoid overdosing with contrast material. Cerebral angiography 10 days later showed thrombosis of the aneurysm sac and normalization of the blood flow in the basilar artery. The patient has been followed up for 2 years and showed good clinical and angiographic outcome. Stenting results in obliteration of the aneurysm sac, so a two-stage procedure is recommended.


Growing teratoma syndrome in a patient with a non-germinomatous germ cell tumor in the neurohypophysis--case report.

A 16-year-old woman presented with a non-germinomatous germ cell tumor in the neurohypophysis manifesting as progressive visual disturbance, amenorrhea, hydrodipsia, and polyuria. Her serum alpha-fetoprotein and human chorionic gonadotropin levels were elevated. She experienced sudden, rapid visual deterioration and underwent emergency partial tumor removal to decompress the optic nerves. Her vision subsequently improved. Histological examination of the surgical specimens confirmed immature teratoma. She received chemotherapy (ifosphamide 900 mg/m2, cisplatin 20 mg/m2, etoposide 60 mg/m2) for 5 consecutive days. Although the tumor marker levels decreased remarkably, her vision again declined rapidly due to enlargement of the tumor after the first course of chemotherapy. A second radical operation resulted in vision improvement. The tumor specimen showed only mature teratoma elements. This phenomenon, called the growing teratoma syndrome, is very rare in intracranial non-germinomatous germ cell tumors.


Does multimodality therapy of arteriovenous malformations improve patient outcome?

The strategy for treating arteriovenous malformations (AVMs) has undergone changes and long-term follow-up results remain unclear. To compare the outcomes of different treatment strategies, we divided 112 patients with 113 AVMs into groups with hemorrhagic (n = 71, 62.8%) and nonhemorrhagic (n = 42, 37.2%) AVMs and subdivided these according to the period in which they were treated (before/after 1990). In the more recent period, treatment more frequently involved the use of the gamma-knife and microembolization to the AVM as well as combination therapy. Long-term follow-up showed that the complication rate was lower and the Rankin scale better, in the more recently treated group. Based on our findings we suggest that AVMs should be treated aggressively using a multimodality strategy.


Stroke MRIにおける急性期脳虚血の診断と治療

Stroke MRIにおける急性期脳虚血の診断と治療


Anti-a-fodrin autoantibodies in Moyamoya disease

Moyamoya disease (MMD) is a rare entity that results in progressive occlusion of the arteries of the circle of Willis, but the pathogenesis of MMD is unknown. MMD sera (n=32) were tested for anti-endothelial cell antibodies by enzyme-linked immunoassays and flow cytometric analysis. Apoptosis was induced in human umbilical vein endothelial cells by tumor necrosis factor-alpha. We found that a high proportion of MMD sera had anti-endothelial cell antibodies with apoptotic stimuli. Prominent reactivities of MMD sera (72%) with recombinant human alpha-fodrin were observed. Our study demonstrates that MMD sera contain a high incidence of anti-alpha-fodrin autoantibodies, providing new insight into the mechanisms of occlusion of MMD arteries.


Expression of cell adhesion molecules in chordomas: an immunohistochemical study of 16 cases.

Chordomas are thought to be tumors originating from notochord remnants characterized histologically by cohesive cells with epithelial features and by immunohistochemical expression of epithelial markers. To investigate the expression and distribution of cell adhesion molecules in chordomas, we immunohistochemically studied the expression of representative cell adhesion molecules, E-cadherin, P-cadherin, N-cadherin, beta-catenin, CD44, ICAM-1 (CD54), NCAM (CD56), and VCAM-1 (CD106) in 16 tumors from 16 patients (skull base, n=5; cervical, n=2; sacral, n=9) and 3 cases of fetal notochord. Of 16 tumors, 12 (75.0%) expressed membranous immunoreactivity for NCAM, 10 (62.5%) for VCAM-1, 9 (56.3%) for CD44, 8 (50.0%) for N-cadherin, 6 (37.5%) for beta-catenin, 4 (25%) for ICAM-1, and 1 (6.3%) for P-cadherin. Nuclear staining for E-cadherin was recognized in 11 (68.8%) tumors, and membranous staining for E-cadherin in 3 (18.8%); none of the tumors showed both nuclear and membranous staining. Intranuclear accumulation of beta-catenin was not found in any chordoma. One fetal notochord case showed immunoreactivity for N-cadherin, E-cadherin (some cells showed staining in both cytoplasm and nuclei), CD44 and beta-catenin. These results indicate that chordomas frequently express immunoreactivity for multiple adhesion molecules including VCAM, CD44 and N-cadherin, as well as for NCAM and E-cadherin, as previously reported. These molecules may participate in producing the cellular cohesion evident in tumor morphological structure. Although the precise underlying mechanisms remain to be elucidated, the high frequency of nuclear expression of E-cadherin (11 of 16 cases) may be diagnostically useful.


Diagnosis of acute brain-stem infarcts using diffusion-weighed MRI

There are many reports on acute cerebral infarcts diagnosed by diffusion-weighted MRI (DWI), but few describe brain-stem infarcts diagnosed by this method. Using the apparent diffusion coefficient (ADC), we studied 18 consecutive patients with brain-stem infarcts who underwent DWI during the acute phase. We calculated and compared the ADC ratio (lesion ADC/contralateral ADC) in 10 patients with brain-stem and 23 with supratentorial cortical infarcts examined within 24 h of the onset of stroke. Ischaemic brain-stem lesions were detected in all 15 patients who underwent DWI more than 3 h after the onset, but not in two who had DWI within 3 h of the onset; their ADC ratio was more than 0.95. ADC ratios in patients with brain-stem infarcts decreased as the interval between onset and DWI increased; the decrease was slower than in patients with supratentorial cortical infarcts.


Raised plasma oxidised LDL in acute cerebral infarction

The association between oxidised low density lipoprotein (OxLDL) and cerebral infarction is suspected but not established. To determine whether plasma OxLDL is a useful marker for monitoring oxidative stress in stroke patients. Plasma OxLDL concentrations were determined in 56 stroke patients with cerebral infarction (n = 45) or cerebral haemorrhage (n = 11), and in 19 age matched controls, using a novel sandwich enzyme linked immunosorbent assay. Compared with the controls (0.130 (0.007) ng/ micro g LDL, mean (SEM)), OxLDL was significantly raised in patients with cerebral infarction (0.245 (0.022); p < 0.0001) but not in those with haemorrhage (0.179 (0.023)). Patients with cortical ischaemic infarcts (n = 22) had higher OxLDL levels than either the controls (p < 0.0001) or the patients with non-cortical ischaemic infarcts (n = 23) (p < 0.001). Increased OxLDL concentrations in patients with cortical infarcts persisted until the third day after stroke onset. The National Institutes of Health stroke scales in patients with cortical infarction were higher than in those with non-cortical infarction (p < 0.01). There is a significant association between raised plasma OxLDL and acute cerebral infarction, especially cortical infarction. Plasma OxLDL may reflect oxidative stress in stroke patients.

Journal of Neurology, Neurosurgery, and Psychiatry


高位頸動脈狭窄病変に対するCEA -後頭動脈と狭窄の高さとの検討-

高位頸動脈狭窄病変に対するCEA -後頭動脈と狭窄の高さとの検討-


GH-Secreting Pituitary Adenomas Infrequently Contain Inactivating Mutations of PRKAR1A and LOH of 17q23-24.

The molecular events leading to the development of GH-secreting pituitary tumours remain largely unknown. Gsalpha (GNAS1) mutations are found in 27-43% of sporadic GH-secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4-9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH-secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RIalpha regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) on 17q23-24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH-secreting adenomas in about 10%. We re-evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH-secreting adenomas. We analysed exons 8 and 9 of GNAS1 and all exons and the exon-intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH-secreting pituitary adenomas (30 GH-secreting adenomas, two GH and PRL-secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23-24 with four microsatellite markers and intragenic markers of PRKAR1A. Seventeen of 32 (53.1%) tumours showed somatic-activating mutations of GNAS1: 16 (53.3%) of 30 GH-secreting adenomas and one of two GH and PRL-secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23-24 were detected in any of the tumours examined. We reconfirm the important role of activating mutations of GNAS1 in GH-secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis.


腎透析患者の脳出血の治療と予後の検討

腎透析患者の脳出血の治療と予後の検討


Astroglial expression of D-amino acid oxidase gene


Oxidized LDL in Carotid Plaques and Plasma Associates With Plaque Instability

Oxidation of LDL plays a significant pathogenic role in atherosclerosis. In this study, we attempted to clarify the correlation between the morphology of human atherosclerotic plaques and the oxidized LDL (OxLDL) levels in plasma and carotid plaques. OxLDL levels (ng/microg apolipoprotein B) in plasma and carotid plaques from 44 patients undergoing carotid endarterectomy and OxLDL levels in 17 control plasma and 9 normal intima samples were determined by a sandwich ELISA by using specific antibodies against OxLDL (DLH3) and apolipoprotein B. The plaques were immunohistochemically classified as macrophage (Mphi)-rich and Mphi-poor. In paired samples from individual patients, plaque OxLDL was nearly 70 times higher than plasma OxLDL (mean+/-SEM, 11.9+/-1.7 vs 0.18+/-0.01 ng/microg apoB, P<0.0001). The OxLDL level was significantly higher in Mphi-rich- than Mphi-poor plaques (19.6+/-2.8 vs 5.50+/-0.77 ng/microg apoB, P<0.0001) and corresponded with DLH3 antigen positivity of the plaques. In patients with Mphi-rich plaques, plasma OxLDL was significantly higher than in the controls (0.20+/-0.02 vs 0.13+/-0.01 ng/microg apoB, P=0.02). Our results suggest that LDL undergoes further oxidation in plaques, and that high plasma and plaque levels of OxLDL are correlated with the vulnerability to rupture of atherosclerotic lesions.

Arteriosclerosis, Thrombosis, and Vascular Biology


Gene expression of D-amino Acid oxidase in cultured rat astrocytes

Neuromodulative free D-serine is present in mammalian brain, and localized to type-2 astrocytes in culture. D-amino acid oxidase (DAO) is a flavoenzyme that catalyzes D-amino acids. We examined the DAO gene expression in cultured rat astrocytes by reverse transcriptase-polymerase chain reaction. We established a method to prepare highly purified culture of type-1 and type-2 astrocytes from any brain region. This method utilizes combination of cell type specific separation by shaking and subsequent purification by immunopanning or treatment with cytosine arabinoside. We detected higher DAO gene expression in type-1 astrocyte cultures from cerebellum than that from cerebral cortex. In cerebellum, we observed higher DAO expression in type-1 astrocyte cultures than that in type-2. We also revealed that DAO expression in C6, corresponding to type-1 astrocyte, was higher than that in CG-4 derived type-2 astrocytes.


Integrated EEG monitoring system of brain functions during operations

In some cases, it is necessary to occlude the blood flow in a part of the brain during the surgical procedure. In such cases, it is very important to monitor brain functions, and to do appropriate treatment in order to minimize the postoperative complication. At present, several kinds of equipment specialized to monitor single modality are being used simultaneously. The aim of this study was to develop an EEG monitoring system which integrates various analyzing methods. It can indicate not only single modality information but also multi modality. In addition, the system has great advantages. It can provide complex diagnostic information by synthesizing the results of the multi modality analysis. The system consists of data acquisition, waveform memory management, and data analysis parts. To add a new analyzing method, a corresponding module was added in this part. This system can be used without difficulty because it is composed of simple modules. The first experimental system with the above architecture was made.

本研究では様々解析手法を統合することができるEEGモニタリングシステムの開発を目的としている．様々なモダリティを表示することができ，その診断結果を提示することが可能となる．本システムはデータ取得モジュール，波形メモリモジュール，データ解析モジュールから成り立っており，モジュール構造のため機能の追加が容易である．このようなアーキテクチャを持つ試作機を製作した．


Clinicopathological significance of lipid peroxidation in carotid plaques.

Several reports have suggested an association between lipid peroxidation and human carotid atherosclerosis, but few reports have demonstrated a link between lipid peroxidation and carotid plaques in humans. In this study, we investigated the relationship between clinical features, histopathological characteristics and lipid peroxidation in patients undergoing carotid endarterectomy (CEA). Forty-one carotid plaques were obtained. A portion of the most severe lesions was subjected to histopathologic examination, and the remainder of the plaques examined for lipid peroxidation. Thiobarbituric acid-reactive substances (TBARS) values were determined as a marker for lipid peroxidation. The lipid-rich core (LC) and macrophage infiltration (Mphi) component as a percentage of total plaque area were measured morphometrically. Based on the results, all plaques were classified into four groups. Group I (GI): LC <10%; Group IIa (GIIa): LC 10-30%, Mphi <5%; Group IIb (GIIb): LC 10-30%, Mphi < or = 5%, and Group III (GIII): LC < or =30%. The plaque TBARS values of GIII were significantly higher than those of GI, GIIa, and GIIb. The TBARS values of GIIb were one-and-a-half times higher than those of GIIa. Our results show that lipid peroxidation in carotid plaques is significantly associated with carotid atherosclerosis, especially plaque instability. These findings provide direct evidence of an association between lipid peroxidation and human atherosclerosis.


Can Diffusion- and Perfusion-weighted Magnetic Resonance Imaging Evaluate the Efficacy of Acute Thrombolysis in Patients with Internal Carotid Artery or Middle Cerebral Artery Occlusion?

The value of combined diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) for detecting ischemic lesions of patients with acute ischemic injury was analyzed. Combined pre- and posttreatment DWI and PWI studies were used to assess the efficacy of intra-arterial thrombolysis. Intra-arterial thrombolysis was performed within 6 hours of onset in 10 patients who presented with acute middle cerebral artery or internal carotid artery occlusion. DWI and PWI obtained before and after treatment were studied. The final T2-weighted magnetic resonance scans were obtained 1 month after onset. Thrombolysis resulted in recanalization in seven patients. The mismatch ratio percentage ([initial PWI-initial DWI/initial PWI] x 100) and the rescued ratio percentage ([initial PWI-final T2/initial PWI] x 100) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used for neurological assessment of stroke severity at admission and at 1 month after onset. In all patients, the mismatch ratio was greater than 60% (mean +/- standard deviation, 81.7 +/- 16.7%) and was significantly correlated with initial NIHSS score (-0.74; P = 0.03), and the rescued ratio was significantly correlated with the NIHSS score 1 month after the insult (r = -0.83; P = 0.01). In patients who exhibited recanalization of the occluded artery (n = 7), the mean rescued ratio was 89.6 +/- 12.8% (range, 63-100%). In addition, the lesion volume on posttreatment DWI scans and final T2-weighted magnetic resonance images was not enlarged; on posttreatment PWI scans, it was significantly decreased. The NHISS score at 1 month after the insult (2.3 +/- 2.1) was markedly improved as compared with the initial NHISS score (10.7 +/- 3.9). In a small number of patients who presented with internal carotid artery or middle cerebral artery occlusion, the DWI/PWI mismatch ratio correlated with the initial neurological severity. The rescued ratio may be an objective indicator of the efficacy of treatment.


悪性神経膠腫に対する混合ビームを用いた中性子捕捉療法

悪性神経膠腫に対する混合ビームを用いた中性子捕捉療法


Clinical review of BNCT using mixed neutron beam in patients with malignant glioma, Research and Development in Neutron Capture Therapy