Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma

The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.


徳島大学病院脳卒中センターにおける口腔管理の意義について

徳島大学病院脳卒中センターにおける口腔管理の意義について


Visionary Approach to Sports Head Injury

スポーツ頭部外傷を可視化する

We review current topics in sports-related head injuries including acute subdural hematoma (ASDH) and cerebral concussion. Sports-related ASDH is a leading cause of death and severe morbidity in popular contact sports like American football in the USA and judo in Japan. It is thought that rotational acceleration is most likely to produce not only cerebral concussion but also ASDH due to rupture of a parasagittal bridging vein, depending on the severity of the rotational acceleration injury. Repeated sports head injuries increase the risk for future concussion, cerebral swelling, or ASDH and chronic traumatic encephalopathy (CTE). To avoid fatal consequences or CTE resulting from repeated concussions, an understanding of the criteria for a safe post-concussion return to play is essential. Once diagnosed with a concussion, the athlete must not be allowed to return to play on the same day and should not resume play before the concussion symptoms have completely resolved. If brain damage has been confirmed or a subdural hematoma is present, the athlete should not be allowed to participate in any contact sports. Information on the risk for and management of head injuries in athletes participating in different sports should be widely disseminated in educational institutions and by public relations campaigns of sports organizations. Efforts must be made to educate not only personnel and parents directly involved in the care of athletes but also the general public.

スポーツ頭部外傷の問題点を可視化するために, 今日的話題をレビューした. 急性硬膜下血腫はスポーツ頭部外傷の重症型の中で最も頻度が高く, 軽症例の代表は脳振盪である. いずれも回転加速度損傷を発生機序としている. 脳振盪を繰り返すことによる重症化や慢性外傷性脳症の発生など, 脳振盪への正しい理解と対応が脳神経外科医に求められている. 重症スポーツ頭部外傷を回避するためには, 脳振盪が疑われた当日は競技復帰をさせず, 症状が消失するまでは許可しない, 復帰を許可する場合には段階的復帰プログラムを用いる, 急性硬膜下血腫など器質的病変を有するアスリートに対しては, 原則としてコンタクトスポーツへの競技復帰は許可しないことが推奨される.


Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?

The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.


The two-1 layered susceptibility vessel sign on 3-tesla T2*-weighted imaging is a predictive biomarker of stroke subtype

A susceptibility vessel sign (SVS) on 1.5-tesla (T)-T2*-weighted images may predict cardioembolism. It has also been detected in patients with large artery atherosclerosis. In patients with major vessel occlusion, the SVS was comprised 2 layers on 3T-T2*-weighted images. We assessed the efficacy of 2-layered SVS on 3T-T2*-weighted imaging scans for predicting cardioembolism. Our study included 132 patients who had ischemic stroke within the preceding 24 hours and presented with internal carotid artery or middle cerebral artery occlusion because of cardioembolism or large artery atherosclerosis. We compared 2-layered SVS and SVS on 3T-T2*-weighted imaging scans for their sensitivity, specificity, and diagnostic odds ratio for predicting cardioembolism. We enrolled 132 patients (72 men; mean age, 74.5 years); of these, 63 (47.7%) were presented with cardioembolism. Although the sensitivity of SVS and 2-layered SVS for cardioembolism and large artery atherosclerosis was not statistically different (74.6% and 58.0%, respectively), the sensitivity of 2-layered SVS was significantly higher in patients with cardioembolism (42.9%) than those with large artery atherosclerosis (2.9%; P<0.001). The specificity and diagnostic odds ratio for 2-layered SVS for cardioembolism were 97.1% and 25.1; for SVS they were 42.0% and 2.1, respectively. The specificity of 2-layered SVS for cardioembolism was high. It may be useful for predicting cardioembolism and for the management of patients with acute ischemic stroke.


Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice

Epidemiological studies have indicated that postmenopausal women have a higher incidence of intracranial aneurysms than men in the same age group. To investigate whether estrogen or estrogen receptors (ERs) mediate protective effects against the formation of intracranial aneurysms. Intracranial aneurysms were induced in mice by combining a single injection of elastase into the cerebrospinal fluid with deoxycorticosterone acetate salt hypertension. The mice were treated with estrogen (17β-estradiol), an ERα agonist (propyl pyrazole triol), and an ERβ agonist (diarylpropionitrile) with and without a nitric oxide synthase inhibitor. The ovariectomized female mice had a significantly higher incidence of aneurysms than the male mice, which was consistent with findings in previous epidemiological studies. In ovariectomized female mice, an ERβ agonist, but not an ERα agonist or 17β-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERβ agonist was absent in the ovariectomized ERβ knockout mice. The protective effect of the ERβ agonist was negated by treatment with a nitric oxide synthase inhibitor. The effects of sex, menopause, and estrogen treatment observed in this animal study were consistent with previous epidemiological findings. Stimulation of estrogen receptor-β was protective against the formation of intracranial aneurysms in ovariectomized female mice.


脳梗塞発症後早期からの抗血小板薬使用が予後に及ぼす影響の検討

脳梗塞発症後早期からの抗血小板薬使用が予後に及ぼす影響の検討


T2強調画像で脊髄内に高信号を呈する病変 圧迫骨折を伴い，両下肢の筋力低下で発症した80歳女性


Current topics in sports-related head injuries: A review

We review the current topic in sports-related head injuries including acute subdural hematoma (ASDH), concussion, and chronic traumatic encephalopathy (CTE). Sports-related ASDH is a leading cause of death and severe morbidity in popular contact sports like American football in the USA and judo in Japan. It is thought that rotational acceleration is most likely to produce not only cerebral concussion but also ASDH due to the rupture of a parasagittal bridging vein, depending on the severity of the rotational acceleration injury. Repeated sports head injuries increase the risk for future concussion, cerebral swelling, ASDH or CTE. To avoid fatal consequences or CTE resulting from repeated concussions, an understanding of the criteria for a safe post-concussion return to play (RTP) is essential. Once diagnosed with a concussion, the athlete must not be allowed to RTP the same day and should not resume play before the concussion symptoms have completely resolved. If brain damage has been confirmed or a subdural hematoma is present, the athlete should not be allowed to participate in any contact sports. As much remains unknown regarding the pathogenesis and pathophysiology of sports-related concussion, ASDH, and CTE, basic and clinical studies are necessary to elucidate the crucial issues in sports-related head injuries.


Deep brain stimulation of the thalamic ventral lateral anterior nucleus for DYT6 dystonia.

The thalamic VLa nucleus could serve as an alternative target in DBS therapy for DYT6 dystonia.

Stereotactic and Functional Neurosurgery


Predictors of neurologic deterioration in patients with small-vessel occlusion and infarcts in the territory of perforating arteries

It is difficult to predict neurologic deterioration in patients with small-vessel occlusion (SVO), that is, small infarcts in the territory of cerebral perforating arteries. We reviewed 110 patients with SVO who were admitted to our hospital. We divided them into groups with (n = 32, group 1) and without deterioration (n = 78, group 2) and evaluated their medical records, risk factors, magnetic resonance imaging findings, grade of periventricular hyperintensity (PVH), maximum diameter of the infarct area, and the number of slices showing infarcts on diffusion-weighted images (DWI). Our study population consisted of 110 patients (71 males and 39 females; mean age 69.2 years): 32 (29%) did and 78 (71%) did not suffer deterioration. By univariate analysis, the age, current smoking, history of stroke, maximum diameter of the infarcted area, number of DWI slices with infarcts, frequency of PVH, and PVH grade based on Fazekas classification differed significantly between the 2 groups. By multivariate analysis, conventional risk factors other than PVH and history of stroke were not associated with neurologic deterioration (PVH grade ≥ 2 versus PVH grade ≤ 1, odds ratio 6.72, P = .006; with stroke versus without stroke, odds ratio .21, P = .049). We also found that higher the PVH grade, the worse the National Institutes of Health Stroke Scale score at the time of discharge. PVH and without history of stroke are independently associated with neurologic deterioration in patients with SVO.

Journal of Stroke & Cerebrovascular Diseases


Post-ischemic hyperperfusion after clipping of a reptured internal carotid-posterior communicating artery aneurysm under suction decomperession

Interdisciplinary Neurosurgery: Advanced Techniques and Case Management


Surgical results of lumbor interbody fusion using calcium phosphote cement

Clinical and radiological outcomes of lumbar interbody fusion using artificial fusion cages filled with calcium phosphate cements (CPCs) were retrospectively reviewed. Between 2002 and 2011, 25 patients underwent lumbar interbody fusion at Tokushima University Hospital, and 22 patients were enrolled in this study. Of these, 5 patients received autologous local bone grafts and 17 received CPC. Japan Orthopedic Association (JOA) score was used for clinical outcome assessments. Lumbar radiography and computed tomography (CT) were performed at 12, 24 months and last follow-up period to assess bony fusion. The mean JOA score of all patients improved from 9.3 before surgery to 21.0 at 24 months after surgery. Fusion had occurred in 5 of 5 patients in the local bone graft group and in 16 of 17 patients in CPC group at 24 months postoperatively. No surgically related complication was occurred in both groups. CPC is a useful and safe graft material for lumbar interbody fusion.


私の手術論 脳神経外科医の心・技・体 精力善用，自他共栄

私の手術論 脳神経外科医の心・技・体 精力善用，自他共栄


変形性頸椎症に伴った徐々に増大する随内高輝度病変

変形性頸椎症に伴った徐々に増大する随内高輝度病変


Incidence and predictors of ischemic stroke events during hospitalization in patients with transient ischemic attack

The purpose of this study was to elucidate the incidence and predictors of ischemic stroke or recurrent transient ischemic attack (TIA) during acute hospitalization in patients with TIA. We carried out a multicenter retrospective study to clarify the characteristics of in-patients with TIA. The subjects of this study were TIA patients admitted to 13 stroke hospitals within 7 days after onset between 2008 and 2009. TIA was defined as focal neurologic symptoms ascribable to a vascular etiology lasting less than 24 h. We investigated the incidence and predictors of ischemic events including ischemic stroke or recurrent TIA during hospitalization. A total of 464 patients with TIA (292 men, 69 ± 13 years) were registered. Of those, 400 (86.2%) were admitted within 24 h of TIA onset. The mean length of hospital stay was 13 days. During hospitalization, 8 patients had ischemic strokes and 26 had recurrent TIAs. The leading subtype of 8 ischemic strokes was small vessel disease (n = 3) followed by cardioembolism (n = 2). Multiple logistic regression analysis showed that hypertension (OR: 3.41; 95% CI: 1.23-12.3), MRI-diffusion-weighted image positivity (OR: 2.49; 95% CI: 1.15-5.25), and hemiparesis (OR: 2.30; 95% CI: 1.02-5.88) were independently associated with ischemic events during hospitalization. In this study, 1.7% of patients with TIA had ischemic stroke during acute hospitalization, and the most common subtype was small vessel disease. Subsequent ischemic stroke and recurrent TIA were associated with hypertension, positive DWI findings, and hemiparesis.


Correlation between rediatio dose and histopathological findings in patients with glioblastoma treated with boron neutron capture therapy (BNCT)

The purpose of this study was to clarify the correlation between the radiation dose and histopathological findings in patients with glioblastoma multiforme (GBM) treated with boron neutron capture therapy (BNCT). Histopathological studies were performed on specimens from 8 patients, 3 had undergone salvage surgery and 5 were autopsied. For histopathological cure of GBM at the primary site, the optimal minimal dose to the gross tumor volume (GTV) and the clinical target volume (CTV) were 68Gy(w) and 44Gy(w), respectively.


Evolution of Stroke Emergency System in Tokushima University Hospital

徳島大学病院における脳卒中救急システムの進化

We established the stroke care unit (SCU) for stroke emergency system in Tokushima University Hospital. There were 3,452 patients admitted with acute stroke from 1999 to 2013 in our institute, and 131 patients with acute ischemic stroke were treated with rt-PA (recombinant tissue-type plasminogen activator) intravenous infusion therapy. Revascularization therapy for acute ischemic stroke was done in 20% of patients and rt-PA intravenous infusion therapy in 10.6% of patients. SCU was on track since 2008 and the implementation rate of therapy during this period was 12.8%. The activity of stroke center in our institute promotes improvement of stroke medical level in the region, increase of convalescence rehabilitation facility, and increase in the hospital medical fees. As a result, the stroke center has contributed to medical students and young doctors for the education of stroke. Challenge for the future is the establishment of the treatment system for acute stroke in the medical depopulated area.

要旨:【目的】徳島大学病院では1999 年から脳卒中ケアユニット(SCU)を立ち上げ脳卒中救急医療の確立と改善に努めており，その意義と効果について述べる．【方法】当施設でのSCU 運用の理念と試みは以下に要約される．(1)脳神経外科・神経内科・放射線科・救急集中治療部など各科の医師およびSCU 専任の看護スタッフや多種のコメディカルスタッフが協力して，脳卒中救急に対し24 時間断らないチーム医療を実践する．(2)脳卒中急性期の画像診断は，くも膜下出血例を除き3 テスラMRI(DWI, T2*, MRA)first とし，脳卒中の病型診断や治療方針を即座に決定する．(3)脳虚血救急では，rt-PA 治療適応例には迅速に治療開始し，rt-PA 非適応例やrt-PA 治療無効例においても主幹動脈閉塞によるペナンブラが存在する場合には機械的血栓破砕やステント，バイパスなどの血行再建治療を試みる．(4)2012 年からSCU にスマートフォンとインターネットを用いた脳卒中救急画像転送システム(i-Stroke)を導入し，SCU スタッフ間での情報の共有化と治療方針の適正化を実践した．(5)SCU の9床を1∼2 週で回転し，必ず空床を置き救急を断らないためにベッドコントロールと地域連携を徹底し促進した．【結果】1999 年の開設から2013 年10 月31 日までの脳卒中救急搬送例は3452 例，rt-PA治療は131 例であった．脳梗塞救急例の20%に何らかの血行再建治療，10.6%にrt-PA 治療を行った．SCU が軌道に乗った2008 年以降の実施率は平均12.8%であった．【結論】これらの活動は，地域における脳卒中医療レベルの向上，回復期リハビリ施設の増加と連携の強化，病院診療報酬の増加を促進し，若手医師や学生の脳卒中教育にも大きく貢献している．今後の課題は，県内医療過疎地域の脳卒中救急医療の対策と確立である．


スポーツ頭部外傷における脳振盪の意義と対応

スポーツ頭部外傷における脳振盪の意義と対応


Effect of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease - Results of the Japan adult moyamoya trial-

About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial-intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial-intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan-Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P=0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148-1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan-Meier survival analysis (2.7%/y versus 7.6%/y; P=0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125-1.009). Although statistically marginal, Kaplan-Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000166.


Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: Proposal of an international research group

To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.


Estrogen protects against intracranial aneurysm rupture in ovariectomized mice

Clinical observations suggest that postmenopausal women have a higher incidence of aneurysmal rupture than premenopausal women. We hypothesize that a relative deficiency in estrogen may increase the risks of aneurysmal growth and subarachnoid hemorrhage in postmenopausal women. We assessed the effects of estrogen and selective estrogen receptor subtype agonists on the development of aneurysmal rupture in ovariectomized female mice. We used an intracranial aneurysm mouse model that recapitulates the key features of human intracranial aneurysms, including spontaneous rupture. Ten- to 12-week-old ovariectomized female mice received treatment with estrogen, nonselective estrogen receptor antagonist, estrogen receptor-α agonist, or estrogen receptor-β agonist starting 6 days after aneurysm induction so that the treatments affected the development of aneurysmal rupture without affecting aneurysmal formation. Estrogen significantly reduced the incidence of ruptured aneurysms and rupture rates in ovariectomized mice. Nonselective estrogen receptor antagonist abolished the protective effect of estrogen. Although estrogen receptor-α agonist did not affect the incidence of ruptured aneurysms or rupture rates, estrogen receptor-β agonist prevented aneurysmal rupture without affecting the formation of aneurysms. The protective role of estrogen receptor-β agonist was abolished by the inhibition of nitric oxide synthase. We showed that estrogen prevented aneurysmal rupture in ovariectomized female mice. The protective effect of estrogen seemed to occur through the activation of estrogen receptor-β, a predominant subtype of estrogen receptor in human intracranial aneurysms and cerebral arteries.


The ratio of D-dimer to brain natriuretic peptide may help to differentiate between cerebral infarction with and without acute aortic dissection

Previous studies reported that the plasma d-dimer level reflects the activity of thrombus formation in the left atrium of patients with acute cerebral infarction and acute aortic dissection (AAD). Brain natriuretic peptide (BNP) is considered to be a marker of chronic heart failure. The differential diagnosis in the emergency room between stroke due to cardioembolism and AAD is difficult but important for early treatment especially in patients requiring intravenous thrombolysis with a recombinant tissue-type plasminogen activator. We aimed to investigate the association between the plasma d-dimer and BNP levels in patients with cerebral infarction and AAD. We identified 115 consecutive patients with ischemic stroke who were admitted within 72 h of symptom onset and 15 consecutive patients with AAD and measured the level of plasma d-dimer and BNP and the d-dimer:BNP ratio. In patients with AAD the d-dimer level was significantly higher than that in patients with any other stroke subtypes and their BNP level was significantly lower than that in patients with cardioembolic stroke. The d-dimer:BNP ratio was significantly higher in patients with AAD than in those with any other stroke subtype. Compared to patients with a cardioembolic stroke subtype they manifested significantly higher d-dimer levels and d-dimer:BNP ratios suggesting that this ratio may help to diagnose cerebral infarction due to AAD (sensitivity 80%, specificity 93.5%, cut-off 0.074). When the population was limited to patients within 6h of onset, the ratio had higher sensitivity and specificity at the same cut-off value (sensitivity 81.8%, specificity 96.4%). We found that the d-dimer:BNP ratio may be helpful in distinguishing between cerebral infarction with and without AAD.


Features of patients with transient monocular blindness: a multicenter retrospective study in Japan

Transient monocular blindness (TMB) is associated with a transient ischemic attack (TIA). The purpose of this study was to investigate the features of TMB in the Japanese population using data from a multicenter retrospective study of TIA. The subjects were consecutive TIA patients admitted to 13 stroke centers within 7 days after symptom onset. We compared clinical characteristics of patients with TMB and those without TMB who had other symptoms of cerebral TIA. A total of 464 patients were registered between January 2008 and December 2009, and 444 patients (283 men, mean age: 68.5 years) were included in the analysis. Thirteen patients (2.9%) presented with TMB. Patients with TMB were less likely to arrive at the specialized stroke center quickly than those without TMB (P = .013). Stenotic lesions in the extracranial internal carotid artery were more common in patients with TMB (33.3% versus 9.1%, P = .022). TMB was not common in our TIA inpatients. This study suggests that patients with TMB should immediately undergo a diagnostic workup, including brain and vessel imaging, and cardiac evaluation, as is performed in patients with other cerebral TIA symptoms. A larger, prospective cohort is needed to confirm the risks and outcomes of patients with TMB in the Japanese population.

Journal of Stroke & Cerebrovascular Diseases


Intra-arterial signal on arterial spin labeling perfusion MRI to identify the presence of acute middle cerebral artery occlusion

The susceptibility vessel sign on gradient echo-type-T2*-weighted imaging is a well-known marker of arterial occlusion. Stagnant flow in front of the middle cerebral artery (MCA) occlusion sites may contribute to the intra-arterial, high-intensity signal on arterial spin labeling magnetic resonance imaging (MRI), making it another potential marker of MCA occlusion. We compared the intra-arterial, high-intensity signal and susceptibility vessel sign in patients with symptomatic MCA occlusion and patients without major vessel occlusion. We identified transient ischemic attack or ischemic stroke patients with (1) 3-T MRI performed within 24 h after clinical onset including arterial spin labeling, T2*-weighted imaging, and magnetic resonance angiography (MRA) and (2) either having MCA occlusion (n = 34 patients) or without major vessel occlusion (n = 24 patients). The intra-arterial, high-intensity signal was defined as an enlarged circular or linear bright hyperintensity within the artery. The susceptibility vessel sign was defined as an enlarged spot of hypointensity within the MCA, in which the diameter of the hypointense signal within the vessel exceeded the contralateral vessel diameter. The presence or absence of the intra-arterial, high-intensity signal and susceptibility vessel sign were assessed, along with their inter-rater agreement and consistency with the presence of MCA occlusion on MRA. The intra-arterial, high-intensity signal was detectable in 30 patients (52%), and susceptibility vessel sign was observed in 17 patients (29%). The sensitivity of the intra-arterial high-intensity signal was significantly higher than that of the susceptibility vessel sign (88% vs. 50%; p < 0.05). The accuracy of the intra-arterial high-intensity signal was also higher than that of the susceptibility vessel sign (93% vs. 71%; p < 0.05). The intra-arterial high-intensity signal was situated in the proximal regions of the susceptibility vessel sign on T2*WI within the MCA. Neither the intra-arterial high-intensity signal nor the susceptibility vessel sign was observed in patients without major vessel occlusion. Inter-rater agreement was good for intra-arterial high-intensity signal detection (κ = 0.73) and moderate for susceptibility vessel sign detection (κ = 0.47). The presence or absence of the intra-arterial high-intensity signal was highly consistent with that of MCA occlusion on MRA (κ = 0.74). The intra-arterial high-intensity signal on arterial spin labeling appears to be useful to identify the presence of acute MCA occlusion and may be associated with stagnant flow in front of occlusion sites. The intra-arterial high-intensity signal may also be used to identify the occlusion site.


Reversibility of ischemic findings on 3-tesla magnetic resonance T2(*)-weighted image after recanalization

Ischemic vessel signs (IVS) can be detected on 3-tesla T2(*)-weighted magnetic resonance images as a vessel enlargement at the territory of acute ischemia caused by major vessel occlusion or stenosis. Here, we studied changes in IVS before and after recanalization by the administration of intravenous recombinant tissue plasminogen activator (IV rtPA), carotid artery stenting or percutaneous transluminal angioplasty in patients with major vessel occlusion or stenosis. We performed magnetic resonance imaging for all patients treated by IV rtPA at the time of admission, shortly after and 24-72 hours after treatment with IV rtPA. We reviewed the IVS to assess its natural course of IVS by assessing patients who did not recanalize. IVS tended to disappear after recanalization. Conversely, in patients without recanalization, IVS did not disappear shortly after IV rtPA; rather, it disappeared 24-72 hours after IV rtPA, especially in the presence of complete infarction. Recanalization by IV rtPA or endovascular treatment contributed to improved clinical deficits or the prevention from further progression. IVS can be a parameter of misery perfusion and an important factor to detect the patients who have an indication of treatment for recanalization.

The Journal of Medical Investigation : JMI


Factors associated with onset-to-door time in patients with transient ischemic attack admitted to stroke centers

The aim of this study was to elucidate the factors associated with the time from symptom onset to arrival at a stroke center (onset-to-door time [ODT]) in patients with classically defined transient ischemic attack using data from a multicenter, retrospective study. The subjects were patients with transient ischemic attack admitted to 13 stroke centers in Japan within 7 days of onset between 2008 and 2009. A total of 464 patients registered (292 men, 68.5±13.2 years old), and 421 of them (268 men, 68.8±13.1 years old) were included in the analyses. ODT was classified into the following 5 categories: <3 hours, 3 to 6 hours, 7 to 12 hours, 13 to 24 hours, and >24 hours. There were 233 patients (55.3%) who visited a stroke center within 3 hours of symptom onset. Multiple ordinal logistic regression analysis revealed that motor weakness, speech disturbance, and duration of symptoms >10 minutes were independently associated with a short ODT. Furthermore, a history of transient ischemic attack and hypertension and a referral from another medical facility were independently associated with a long ODT. Patients with a higher ABCD2 score were likely to arrive at a stroke center more quickly. We identified several factors that were positively and negatively associated with the ODT in patients with transient ischemic attack.


Roles of hypertension in the rupture of intracranial aneurysms

Systemic hypertension has long been considered a risk factor of aneurysmal rupture. However, a causal link between systemic hypertension and the development of aneurysmal rupture has not been established. In this study, using a mouse model of intracranial aneurysm rupture, we examined the roles of systemic hypertension in the development of aneurysmal rupture. Aneurysms were induced by a combination of deoxycorticosterone acetate (DOCA)-salt and a single injection of elastase into the cerebrospinal fluid in mice. Antihypertensive treatment was started 6 days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysm with subarachnoid hemorrhage. Hydralazine (direct vasodilator) or discontinuation of DOCA-salt treatment was used to assess the roles of systemic hypertension. Captopril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin II type 1 receptor antagonist) was used to assess the roles of the local renin-angiotensin system in the vascular wall. Normalization of blood pressure by hydralazine significantly reduced the incidence of ruptured aneurysms and the rupture rate. There was a dose-dependent relationship between reduction of blood pressure and prevention of aneurysmal rupture. Captopril and losartan were able to reduce rupture rate without affecting systemic hypertension induced by DOCA-salt treatment. Normalization of blood pressure after aneurysm formation prevented aneurysmal rupture in mice. In addition, we found that the inhibition of the local renin-angiotensin system independent from the reduction of blood pressure can prevent aneurysmal rupture.


Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma: A case report,

Boron neutron capture therapy (BNCT) has been reported to be effective in the patients with glioblastoma multiforme (GBM). Median survival time (MST) of GBM patients treated with BNCT is approximately two years. GBM patients surviving 2 or 3 years are considered long-term survivors. In general, most recurrences are local and dissemination is rare. We report an unusual patient with three recurrences; the first and the second recurrences were local, and the third recurrence was dissemination nine years after BNCT.


Treatment Outcomes in Patients Older than 80 Years Presenting with Ruptured Intracranial Aneurysms

80歳以上の破裂脳動脈瘤の治療成績

While the number of elderly patients who presented with aneurysmal subarachnoid hemorrhage (SAH) has been increasing, its optimal management in that population remains controversial. Therefore, we retrospectively reviewed the treatment outcomes in 49 consecutive patients aged between 80 and 94 years who presented with SAH. The neurological World Federation of Neurological Surgeons (WFNS) grade at the time of admission was Grade I in 7, Grade II in 11, Grade III in 8, Grade IV in 13, and Grade V in 10 patients. Of the 49 patients, 28 underwent coil embolization, and 7 (25%) had a favorable outcome (mRS: 0-2) at discharge, while in 21 (75%) the outcome was poor (mRS: 3-6). Six patients underwent clipping; the outcome was favorable in one patient (17%) and poor in 5 (83%). Of 15 patients under conservative therapy none had a favorable outcome. A low WFNS grade (I-II) was significantly associated with a favorable outcome (p<0.05). Although the treatment outcome in elderly patients with SAH was poor, radical treatment of ruptured aneurysms should be considered if their WFNS grade is low.


Brush sign on 3-T t2*-weighted MRI as a potential predictor of hemorrhagic transformation after tissue plasminogen activator therapy

The brush sign (BS) is the enlargement of medullary veins on 3-T T2*-weighted MRI seen in patients with ischemic stroke because of major cerebral artery occlusion. However, the clinical relevance of BS in patients with acute stroke remains unclear. We assessed the correlation between detecting BS with the development of hemorrhagic transformation after intravenous thrombolysis. We enrolled consecutive patients with M1 or M2 occlusion treated with intravenous tissue plasminogen activator. We classified the patients into 2 groups: the group positive for BS (P-BS) and the group negative for BS (N-BS). We investigated the differences in MRI findings and the clinical outcome between the 2 groups. The subjects consisted of 36 patients (19 men; mean age, 74.7 years). Twenty-one patients (58%) had M1 occlusion, and 15 (42%) had M2 occlusion. Twenty-five patients (69%) were classified into the P-BS group and 11 (31%) into the N-BS group. Recanalization was observed in 15 (60%) and 10 (90%) patients in the P-BS and N-BS groups, respectively (P=0.116). Hemorrhagic transformation on MRI was observed more frequently in the P-BS group than in the N-BS group (64% versus 18%; P=0.027). A good outcome (mRS, 0-1) at discharge was found in 24% of patients in the P-BS group and in 45% of patients in the N-BS group (P=0.152). A multivariate logistic regression analysis revealed that the presence of BS (odds ratio, 9.08; 95% confidence interval, 1.4-59.8; P=0.022) was independently associated with hemorrhagic transformation. BS may predict the development of hemorrhagic transformation in patients with acute stroke treated with intravenous tissue plasminogen activator.


徳島のスマートフォンを利用した包括的遠隔診療支援 ー脳卒中センターから医療過疎地域支援までー


当科で経験した難治性疼痛に対する脊髄刺激療法の検討 ー特にパーキンソン病に伴う腰下肢痛に関してー


Nihon Rinsho. Japanese Journal of Clinical Medicine


悪性胚細胞腫瘍に対する外科的治療の意義と化学治療の選択

悪性胚細胞腫瘍に対する外科的治療の意義と化学治療の選択

日本内分泌学会雑誌:第24回日本間脳下垂体腫瘍学会Proceeding

日本内分泌学会雑誌:第24回日本間脳下垂体腫瘍学会Proceeding


The Journal of the Japan Medical Association


Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

The Journal of Medical Investigation : JMI


Acquired pial and dural arteriovenous fistulae following superior sagittal sinus theombosis in patients with protein S deficiency: A report of two cases

Two patients with protein S deficiency with acquired multiple pial and dural arteriovenous fistulae (AVFs) following superior sagittal sinus (SSS) thrombosis are reported. Case 1 is a 38-year-old male with protein S deficiency who developed generalized seizure due to SSS thrombosis. Local fibrinolysis was achieved in the acute stage. His 10-month follow-up angiogram revealed an asymptomatic acquired dural AVF arising from the middle meningeal artery and the anterior cerebral artery with drainage to the thrombosed cortical vein in the right frontal lobe. Furthermore, his 2-year follow-up angiogram revealed a de novo pial AVF from the middle cerebral artery in the Sylvian fissure with drainage to the cortical vein initially thrombosed. However, this asymptomatic pial AVF caused bleeding in the ipsilateral cerebral hemisphere 12 years after onset, whereas the dural AVF spontaneously disappeared. Surgical disconnection was successfully performed to eliminate the source of hemorrhage. Case 2 is a 50-year-old male with a past history of SSS thrombosis with protein S deficiency who developed pulsatile tinnitus and generalized seizure. His angiogram showed a cortical dural AVF in the left parietal lobe and a sporadic dural AVF involving the right sigmoid sinus. The parietal lesion was eliminated by transarterial embolization followed by craniotomy. However, a de novo pial AVF emerged from the middle cerebral artery adjacent to the previously treated lesion. Of four cortical AVFs in two patients, thrombosis of cortical veins caused by protein S deficiency might play an important role in their formation. Long-term follow-up is required because this peculiar disorder has an unusual clinical course.


Introduction of Tokushima Prefectural Kaifu Hospital telemedicine support system (k-support) using a smartphone and the Internet

スマートフォンとインターネットを用いた徳島県立海部病院遠隔医療支援 システム(k-support)の導入

Because a specialist in general medical treatment lacked the Kaifu area of South Tokushima absolutely, we forced a limited doctor to many burdens and performed medical treatment while I always carried risks on my back for the disease except the specialty domain. A stroke specialist in particular is an absent medical depopulated area, and it is difficult to perform the rt-PA IV therapy that is a standard therapy for a stroke for the immediate nature period. Using remote video diagnosis treatment supporting system SYNAPSE ERm that was the smartphone application that FUJIFILM developed for the purpose of canceling these, we introduced smartphone and Tokushima Prefectural Kaifu Hospital remoteness medical treatment support system (k-support) by the Internet as area medical treatment support in February, 2013. This system can provide image information and patient information such as CT or the MRI to a tablet phone and the smartphone of Tokushima Prefectural Kaifu Hospital full-time employment doctors and the doctors who support it, and work in a House in real time. In other words, we can obtain necessary information without asking the when and where and can send appropriate instructions, advice to the Tokushima Prefectural Kaifu Hospital medical attendant from a specialist for it. After introduction, the treatment with this system in 58 emergency patients was carried out in seven months until August 31. The example letting the wide area present the smartphone such as this system and a remote medical treatment support system using the Internet in the medical depopulated area is the first trial in this country.


Pathogenesis and Natural History of Brain Arteriovenous Malformation and Dural Arteriovenous Fistula

脳動静脈奇形と硬膜動静脈瘻の成因と自然歴


高次脳機能障害スクリーニングテスト Hibrid-STT作成の試みと有用性について


[Differential diagnosis of and therapy for anaplastic astroblastoma: case report and review of the literature].

Astroblastomas are rare glial tumors. We report a case of 33-year-old woman with high-grade astroblastoma with hypervascularity. She had a one-month history of right visual disturbance and papillar edema. MRI revealed a lobulated mass with cysts and flow voids in the right superficial frontal lobe, a phenomenon described as "bubbly appearance". Right carotid angiography demonstrated marked tumor stain and early venous filling. MR spectroscopy showed an increase in myoinositol and the choline/creatine ratio, and decreased N-acetyl aspartate. The lipid and lactate level was not increased. The well-circumscribed tumor was totally resected. Histological examination showed perivascular pseudorosettes and hyalinization of blood vessels with high cellularity, anaplastic nuclear features, focal necrosis, mitosis, and endothelial proliferation. Immunohistochemically, glial fibrillary acidic protein and S-100 protein were intensely positive and the MIB-1 labeling index was high(20%)in the tumor cells. Based on these findings, a diagnosis of high-grade astroblastoma was made. The patient received postoperative radiotherapy and chemotherapy with temozolomide and suffered no relapse in the course of 3 years after surgery. Characteristically, astroblastomas manifest a "bubbly appearance" and a lobulated mass on MRI scans. As these tumors tend to be hypervascular, angiograms are useful for designing the operative strategy. However, their low-or high grade is difficult to ascertain preoperatively based on MRI-, MRS-, and DSA findings. The standard therapy for high-grade astroblastoma is total resection and postoperative radiation therapy. As the incidence of tumor recurrence is high, we recommend additional chemotherapy with TMZ.


今，動脈硬化はこう治療する 頸動脈病変

今，動脈硬化はこう治療する 頸動脈病変


Catastrophic head and neck injuries in Judo players in Japan from 2003 to 2010

Few studies have documented catastrophic head and neck injuries in judo, but these injuries deserve greater attention. To determine the features of catastrophic head and neck injuries in judo. Descriptive epidemiological study. This study was based on the accident reports submitted to the All Japan Judo Federation's System for Compensation for Loss or Damage. A total of 72 judo injuries (30 head, 19 neck, and 23 other injuries) were reported between 2003 and 2010. The investigated parameters were mechanism of injury, age at time of injury, length of judo experience, diagnosis, and outcome. Among head injuries, 27 of 30 (90%) occurred in players younger than 20 years of age. The relationship between age, mechanism, and location of injury was more relevant when players younger than 20 years incurred head injury while being thrown (P = .0026). Among neck injuries, 13 of 19 (68%) occurred in players with more than 36 months of experience. The relationship between experience, mechanism, and location of injury was more relevant when experienced players incurred neck injury while executing an offensive maneuver (P = .0294). Acute subdural hematoma was diagnosed in 94% of head injuries. The outcomes of head injury were as follows: 15 players died; 5 were in a persistent vegetative state; 6 required assistance because of higher brain dysfunction, hemiplegia, or aphasia; and 4 had full recovery. Among neck injuries, 18 players were diagnosed with cervical spine injury, 11 of whom had fracture-dislocation of the cervical vertebra; there was also 1 case of atlantoaxial subluxation. The outcomes of neck injury were as follows: 7 players had complete paralysis, 7 had incomplete paralysis, and 5 had full recovery. Neck injuries were associated with having more experience and executing offensive maneuvers, whereas head injuries were associated with age younger than 20 years and with being thrown.


The ARNT-STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ+CD8αα+cells.

Intestinal intraepithelial T cells contribute to the regulation of inflammatory responses in the intestine; however, the molecular basis for their development and maintenance is unknown. The aryl hydrocarbon receptor complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and senses environmental factors, including gut microbiota. Here, we identify ARNT as a critical regulator of the differentiation of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells. Mice deficient in either ARNT or aryl hydrocarbon receptor show a greater than- eight-fold reduction in the number of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells. The number of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells is increased by treatment with an aryl hydrocarbon receptor agonist in germ-free mice and is decreased by antibiotic treatment. The Arnt-deficient precursors of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells express low amounts of STAT3 and fail to differentiate towards the TCRαβ(+)CD8αα(+) cell fate after IL-15 stimulation, a deficiency that is overcome by overexpression of Stat3. These data demonstrate that the ARNT-STAT3 axis is a critical regulator of TCRαβ(+)CD8αα(+) intestinal intraepithelial T-cell development and differentiation.


Stroke in evolutionを呈する急性期頸動脈狭窄症に対する血行再建術


Response of striosomal opioid signaling to dopamine depletion in 6-hydroxydopamine-lesioned rat model of Parkinsons disease: a potential compensatory role

The opioid peptide receptors consist of three major subclasses, namely, μ, δ, and κ (MOR, DOR, and KOR, respectively). They are involved in the regulation of striatal dopamine functions, and increased opioid transmissions are thought to play a compensatory role in altered functions of the basal ganglia in Parkinson's disease (PD). In this study, we used an immunohistochemistry with tyramide signal amplification (TSA) protocols to determine the distributional patterns of opioid receptors in the striosome-matrix systems of the rat striatum. As a most striking feature of striatal opioid anatomy, MORs are highly enriched in the striosomes and subcallosal streak. We also found that DORs are localized in a mosaic pattern in the dorsal striatum (caudate-putamen), with heightened labeling for DOR in the striosomes relative to the matrix compartment. In the 6-hydroxydopamine-lesioned rat model of PD, lesions of the nigrostriatal pathways caused a significant reduction of striatal labeling for both the MOR and DOR in the striosomes, but not in the matrix compartment. Our results suggest that the activities of the striosome and matrix compartments are differentially regulated by the opioid signals involving the MORs and DORs, and that the striosomes may be more responsive to opioid peptides (e.g., enkephalin) than the matrix compartment. Based on a model in which the striosome compartment regulates the striatal activity, we propose a potent compensatory role of striosomal opioid signaling under the conditions of the striatal dopamine depletion that occurs in PD.


福岡大学医学部柔道部における脳振盪の実態調査

福岡大学医学部柔道部における脳振盪の実態調査


Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism.

Neuropeptide Y is a novel bioactive substance that plays a role in the modulation of neurogenesis and neurotransmitter release, and thereby exerts a protective influence against neurodegeneration. Using a sensitive immunohistochemical method with a tyramide signal amplification protocol, we performed a post-mortem analysis to determine the striatal localization profile of neuropeptide Y in neurologically normal individuals and in patients with X-linked dystonia-parkinsonism, a major representative of the neurodegenerative diseases that primarily involve the striatum. All of the patients examined were genetically verified as having X-linked dystonia-parkinsonism. In normal individuals, we found a scattered distribution of neuropeptide Y-positive neurons and numerous nerve fibres labelled for neuropeptide Y in the striatum. Of particular interest was a differential localization of neuropeptide Y immunoreactivity in the striatal compartments, with a heightened density of neuropeptide Y labelling in the matrix compartment relative to the striosomes. In patients with X-linked dystonia-parkinsonism, we found a significant decrease in the number of neuropeptide Y-positive cells accompanied by a marked loss of their nerve fibres in the caudate nucleus and putamen. The patients with X-linked dystonia-parkinsonism also showed a lack of neuropeptide Y labelling in the subventricular zone, where a marked loss of progenitor cells that express proliferating cell nuclear antigen was found. Our results indicate a neostriatal defect of the neuropeptide Y system in patients with X-linked dystonia-parkinsonism, suggesting its possible implication in the mechanism by which a progressive loss of striatal neurons occurs in X-linked dystonia-parkinsonism.


Frequency of emerging positive diffusion-weighted imaging in early repeat examinations at least 24 h after transient ischemic attacks

The relationships between diffusion lesions and risk scores for patients with a Transient ischemic attack (TIA) and the optimal timing for diffusion lesion screening have not been characterized. The purpose of our study was to evaluate the appearance of diffusion-weighted imaging (DWI) lesions during follow-up examinations of patients with TIA or minor stroke without initial DWI lesions. We identified 31 patients who did not show diffusion lesions in initial DWI. A second magnetic resonance imaging (MRI) examination was performed 24 h after the initial MRI, and the patients were divided into two groups based on the results. Demographic and clinical data, including initial National Institutes of Health Stroke Scale scores, ABCD and ABCD(2) scores, and other MRI findings were evaluated. The data were analyzed using Spearman's rank tests and unpaired t tests. Ten patients (32.3 %) showed diffusion lesions on the second DWI examination. Both risk scores were higher in these patients compared with patients with negative results on follow-up DWI (P < 0.05, unpaired t test) and correlated with the length of the TIA (R s = 0.017, P < 0.05; R s = 0.003, P < 0.01; Spearman's rank test). Our results suggest that TIA patients with high-risk scores might be underestimated if the first MRI was performed within 24 h of symptom onset.


スポーツ頭部外傷における脳神経外科医の対応-ガイドライン作成に向けた中間提言-

スポーツ頭部外傷における脳神経外科医の対応-ガイドライン作成に向けた中間提言-


脳動脈瘤におけるNa+蓄積とRASの影響

脳動脈瘤におけるNa+蓄積とRASの影響


Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice

Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum.


Basal ganglia hyperintensity on T1-weighted imaging of a patient with central nervous system metastasis producing carcinoembryonic antigens

We herein report unusual basal ganglia hyperintense lesions on noncontrast T1-weighted magnetic resonance imaging in a patient with central nervous system metastasis from lung adenocarcinoma that was treated with gefitinib. T2*-weighted magnetic resonance imaging showed no hypointense lesions, thereby excluding the possibility of calcification or haemorrhage. A stereotactic brain biopsy of the left basal ganglia lesions revealed atypical cells, some of which formed a glandular lumen with a micropapillary pattern. These cells were immunopositive for markers of lung adenocarcinoma, thereby confirming the diagnosis of metastasis. We speculate that proteins, including carcinoembryonic antigens from the adenocarcinoma cells in the basal ganglia, may have contributed to the hyperintensity observed on noncontrast T1-weighted magnetic resonance imaging.


特集 大きく変貌した脳梗塞の診断と治療 慢性期治療(二次予防) 外科治療の適応

特集 大きく変貌した脳梗塞の診断と治療 慢性期治療(二次予防) 外科治療の適応


A Case of Cervical Extradural Arteriovenous Fistula presenting with Radiculopathy

Radiculopathy で発症した頚椎硬膜外病変の1例


整容的前頭側頭開頭の画像評価-側頭筋膜間脂肪層の変化に着目して-

整容的前頭側頭開頭の画像評価-側頭筋膜間脂肪層の変化に着目して-

第6回日本脳神経外科研究会講演集

第6回日本脳神経外科研究会講演集


Significance and future perspective of stroke care unit in Tokushima university hospital

徳島県の救急医療と地域医療:現状と展望 徳島大学病院における脳卒中ケアユニットの意義と今後の課題

Cerebral Stroke such as cerebral infarction, intracerebral hemorrhage and subarachnoid hemorrhage is a leading cause of being a bed-ridden state, thus measures against cerebral stroke are still ongoing issue. The university hospital which provides optimal treatment using advanced techniques must struggle to develop emergency medicine including acute cerebral stroke management. Stroke care unit was founded in 1999 in Tokushima university hospital and has contributed to educate medical students, to train junior residents and to promote clinical research with multidisciplinary approach. Furthermore, we adopted i-Stroke system which allows us to browse clinical data including radiological images and to discuss each other by smartphone. This system provided urgent management decision in acute stroke and contribute to improvement not only patients' outcome but physicians' quality of life. The university hospital must also construct a supporting system on medically underpopulated region in future.


The present conditions of the emergency care of South Tokushima and new action : From a neurosurgical viewpoint

徳島県の救急医療と地域医療:現状と展望 徳島県南部の救急医療の現状と新たな取り組み -脳神経外科の立場から-

A regular neurosurgeon was absent in the southern part II health demographic division of medical services where Kaifu-gun of South Tokushima was located after 2008 and was the present conditions that stroke treatment could not perform enough in comparison with prefecture central part. Furthermore, medical care collapse progressed with the obstetrics and gynecology department and pediatrics closedown at one sweep from the same period and, at the prefectural Kaifu Hospital which was this local nucleus hospital, became hard to maintain the emergency care, and increase of closedown of the emergency outpatient department on Saturday and the emergency transportation to the prefecture central part became remarkable, and it was with a big social problem for Tokushima. A medical difference might occur about stroke medical care in central part and the southern part in Tokushima. We performed the epidemiology survey by stroke patient in the southern II demographic division of medical services (popular name ``Kaifu project'') as a President of University of Tokushima discretion project for this fact-finding individually in the University of Tokushima neurosurgery classroom. In addition, I worked on the enlightenment for inhabitants in Kaifu-gun. ``Local neurosurgical medical treatment part'' was established as a college course financially maintained by private donations of Tokushima University Hospital from November 1，2011． Kaifu Hospital neurosurgery medical treatment was enabled daylong, and emergency correspondence came to be in this way possible. The Kaifu Hospital devises the maintenance policy about Tokushima, local inhabitants, a medical association, a local government and the figure which there should be of ``the new Kaifu Hospital'' for a tsunami now in the plan of the full-scale reconstruction move to the hill in 2015．


A clinical study on severe neurogenic stress cardiomyopathy after subarachnoid hemorrhage


脳神経外科手術における綿片カウントのリスクマネジメント -脳神経外科医の立場から-


Activation of signal transducer and activator of transcription-3 by a peroxisome proliferator-activated receptor gamma agonist contributes to neuroprotection in the peri-infarct region after ischemia in oophorectomized rats

The role of the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) after cerebral ischemia by the peroxisome proliferator-activated receptor (PPAR) agonist pioglitazone (PGZ) remains controversial. Whether the increase in p-STAT3 by estrogen is mediated by the estrogen receptor is also obscure. We examined the role of p-STAT3, PPAR, and estrogen receptor against ischemic brain damage after PGZ treatment. Female Wistar rats subjected or not subjected to bilateral oophorectomy were injected with 1.0 or 2.5 mg/kg PGZ 2 days, 1 day, and 1 hour before 90-minute middle cerebral artery occlusion-reperfusion and compared with vehicle-control rats. The cortical infarct size was larger in ovariectomized than in nonovarietomized rats; it was reduced by PGZ treatment. Inversely with the reduction of the infarct size, PPAR, and p-STAT3 but not estrogen receptor in the peri-infarct area were increased in PGZ-treated compared with vehicle-control rats. The increase in PPAR and p-STAT3 was associated with the transactivation of antiapoptotic and survival genes and the reduction of caspase-3 in this area. Inhibitors of PPAR or STAT3 abolished the PGZ-induced neuroprotection and the increase in p-STAT3. More importantly, p-STAT3 increased by PGZ was bound to PPAR and the complex translocated to the nucleus to dock to the response element through p-STAT3. Our findings suggest that the activation in the peri-infarct region of p-STAT3 and PPAR by PGZ is essential for neuroprotection after ischemia and that PGZ may be of benefit even in postmenopausal stroke patients.


Increase in body Na+-to-water ratio is associated with cerebral aneurysm formation in oophorectomized rats

The incidence of cerebral aneurysms is higher in women than in men, especially postmenopause. Although hypertension is thought to be associated with a high incidence of stroke, not all patients with unruptured cerebral aneurysms are hypertensive. The possibility of water-free Na(+) storage associated with hypertension has been raised. However, whether the increase in the body Na(+)/water ratio that characterizes water-free Na(+) accumulation is associated with the formation of cerebral aneurysms remains obscure. To examine this relationship, Sprague-Dawley female rats subjected to carotid artery ligation were divided into 3 groups: a high-salt diet group (HSD) without and another with bilateral oophorectomy (HSD/OVX) and a third group that underwent additional renal artery ligation (HSD/OVX/RL). Compared with rats receiving a normal diet (shams), water retention was increased in HSD rats but not in HSD/OVX rats. Interestingly, compared with HSD rats, the incidence of cerebral aneurysms and the body Na(+)/water ratio were significantly higher in HSD/OVX and HSD/OVX/RL rats, independent of hypertension. In their aneurysmal wall, ATP12, a subtype of Na(+)/K(+)-ATPase, was downregulated, whereas inflammatory-related molecules were upregulated. Treatment with low-dose olmesartan that did not affect the blood pressure in hypertensive HSD/OVX/RL rats reduced the rate of cerebral aneurysm formation, body Na(+) retention, and the Na(+)/water ratio and upregulated ATP12. These results suggest that the increase in the Na(+)/water ratio and a reduction in ATP12 may be associated with cerebral aneurysm formation. We provide the new insight that the management of water-free Na(+) is important to prevent their development.


Effect of statin therapy on carotid artery plaque assessed by integrated backscatter color mapping : Development of imaging analytical software and its application on 3 cases

脂質低下療法による頸動脈プラーク安定化の評価:超音波integrated backscatterを用いたカラーマッピングシステムの開発と臨床応用 症例報告 (第28回 徳島医学会賞受賞論文)

Background : The carotid plaque vulnerability is related to myocardial and cerebral infarction.We intended to develop an imaging system which enables to visualize tissue characteristics in thecarotid plaques based on ultrasound integrated backscatter(IB). And to test its clinical efficacy,effect of the statin therapy on the plaques was evaluated with our software. Methods and Results :Carotid ultrasound examination was performed and ultrasonographic RAW data of the plaqueswere obtained from8patients undergoing carotid artery endarterectomy. Tissue characteristicsin the plaques of resected examples were compared with preoperative ultrasonic images and thetissue IB values corresponding to the specimens were determined for developing our imaging system.Using this system, Color-coded maps of plaques in the three patients were constructed beforeand after lipid lowing therapy. We could demonstrate that lipid fraction in each plaque decreasedand fibrous or calcification fraction increased in the follow-up study. Conclusions : Changes inhistology of carotid plaques by statin could visualized with our imaging system. This techniquemay become a useful tool for the management of atherosclerosis.


Generalized dystonia in a patient with a novel mutation in the GLUD1 gene


A proposal for standardized analysis of the results of microvascular decompression for trigeminal neuralgia and hemifacial spasm

The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner. Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair. The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59). The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.


Evaluating stroke treatment in the south Tokushima ? medical areas without stroke specialists

脳卒中専門医不在地域における脳卒中治療と予後の検討

INTRODUCTION:For cranial nerve diseases, particularly stroke, early-stage treatment by stroke specialists cansignificantly alter patient prognosis. With respect to the treatment of acute cerebral infarction, t‐PAwas approved for health insurance coverage in Japan in November2005, and has greatly influencedmedical practice. However, the use of t‐PA necessitates an expertise in stroke treatment, and thedrug cannot be used in areas where stroke specialists are absent. Consequently, disparities maybe occurring in stroke treatment among different areas. We accordingly aimed to evaluate strokepatients in the south Tokushima Ⅱ medical areas(south Ⅱ medical areas)without stroke specialistsand those transferred to the stroke care unit in the Stroke Center of Tokushima UniversityHospital(Tokushima University Hospital SCU), and to clarify the presence or absence of disparitiesin area-based stroke treatment in Tokushima.METHODS:The subjects were103stroke patients in the south Tokushima Ⅱ medical areas without strokespecialists and 317 stroke patients in Tokushima University Hospital SCU, who were assessedbetween October1，2009and September30，2010.RESULTS:In the areas without stroke specialists, the prognosis of42% of the cerebral infarction patientswas related to the absence of stroke specialists, and to geographical disadvantages. In48% of thecerebral infarction patients in the areas without stroke specialists, the lapse time after the onset ofcerebral infarction exceeded3h at their initial examinations. However, this is considered likely tobe improved by the implementation of stroke awareness activities.DISCUSSION:Cerebral infarction, which is common in the elderly, is expected to increase in frequency andseverity in the future. Therefore, rigorous prevention, awareness activities to spread super-acutestroke treatment using t‐PA, and medical environmental improvement are necessary.


Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma

Interferon-beta (IFN-) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN--induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.


Autopsy case of amebic granulomatous meningoencephalitis caused by Balamuthia mandrillaris in Japan

Balamuthia mandrillaris is a free-living ameba that causes amebic encephalitis. Herein, we report an autopsy case of Balamuthia encephalitis proven with polymerase chain reaction (PCR) and immunohistochemistry from paraffin-embedded brain biopsy specimens. A 68-year-old Japanese male presented at a hospital with progressive right hemiparesis approximately 3 months before his death. An open-brain biopsy specimen showed diffuse meningitis with massive coagulative necrosis. The perivascular spaces contained numerous lymphocytes, histiocytes and giant cells, although the etiology was not determined. The patient deteriorated into coma and died from cerebral herniation. Autopsy revealed abundant trophozoites and cysts in the subarachnoid and Virchow-Robin's spaces. Electron-micrographs of the amebic cysts showed a characteristic triple-walled envelope. The amebas were identified as Balamuthia mandrillaris based on immunohistochemical analysis from the autopsy and biopsy specimens. Primer sets designed to amplify approximately 200 bp bands of mitochondrial 16S rRNA gene of Balamuthia by PCR produced positive results from the biopsy specimens but negative results from the autopsy specimens. In summary, PCR to amplify shorter segments of DNA may be of diagnostic value in detecting suspected cases of balamuthiasis in formalin-fixed, paraffin-embedded specimens. Increased awareness and timely diagnosis of Balamuthia encephalitis might lead to earlier initiation of therapy and improved outcome.


Aneurysm of the lateral spinal artery: A case report


一過性脳虚血発作患者における拡散強調画像の意義と落とし穴

一過性脳虚血発作患者における拡散強調画像の意義と落とし穴


Cell type-specific localization of optineurin in the striatal neurons of mice: Implications for neuronal vulnerability in huntington's disease

Striatal neuropathology of Huntington's disease (HD) involves primary and progressive degeneration of the medium-sized projection neurons, with relative sparing of the local circuit interneurons. The mechanism for such a patterned cell loss in the HD striatum continues to remain unclear. Optineurin (OPTN) is one of the proteins interacting with huntingtin and plays a protective role in several neurodegenerative disorders. To determine the cellular localization pattern of OPTN in the mouse striatum, we employed a highly sensitive immunohistochemistry with the tyramide signal amplification system. In this study, we show that OPTN appeared as a cytoplasmic protein within the subsets of the striatal neurons. Of particular interest was that OPTN was abundantly expressed in the interneurons, whereas low levels of OPTN were observed in the medium projection neurons. This cell type-specific distribution of OPTN in the striatum is strikingly complementary to the pattern of neuronal loss typically observed in the striatum of patients with HD. We suggest that OPTN abundance is an important cellular factor in considering the cell type-specific vulnerability of striatal neurons in HD.


Clinical characteristics of X-linked dystonia-parkinsonism


[Severe head injuries during Judo practice].

柔道における重症頭部外傷

The goal of this study is to elucidate the characteristic features of Judo head injuries and to propose safety measures and a reaction manual on how to prevent and to deal with such accidents in Japan. Thirty cases of severe head injuries suffered during Judo practice were enrolled in this study. They have made insurance claims for damage compensation and inquiries about Judo accidents attributed to the All Japan Judo Federation, from 2003 to 2010. The average age of the patients was 16.5 year old. The incidence of injury showed 2 peaks in different academic grade levels; one is in the first year of junior high-school (30.0%, n=9) and the other is in senior high school (26.7%, n=8). Around half of them were beginners. Four cases (13.3%) had past history of head trauma or headache and dizziness before a catastrophic accident, suggesting the presence of a second impact. Lucid interval was observed in 25 cases (83.3%). Most patients (93.3%) suffered acute subdural hematoma associated with avulsion of a cerebral bridging vein. Of patients who underwent emergency removal of the hematoma, 15 patients (50%) died and 7 patients (23.3%) entered a persistent vegetative state. Based on these findings, we propose an emergency manual with safety measures for effectively preventing and treating Judo head injuries in an appropriate manner. To reduce the disastrous head injuries in Judo, the safety measures and an optimal action manual should be reconsidered and widely spread and accepted by society.


Krüppel-like zinc-finger transcription factor 5 (KLF5) is highly expressed in large and giant unruptured cerebral aneurysms.

Krüppel-like zinc-finger transcription factor 5 (KLF5), known as BTEB2 and IKLF, has several biological functions that involve cell proliferation, development, and apoptosis. In human cerebral aneurysms, macrophage infiltration is profoundly associated with growth and rupture, but the role of KLF5 remains unclear. We examined the significance of KLF5 expression in cerebral aneurysms. Unruptured (n=15) and ruptured (n=12) aneurysms obtained at surgery or autopsy were divided into 3 size groups: small (<10 mm); large (10 mm but <25 mm); and giant (25 mm). Control samples comprised 5 cerebral arteries obtained from surgery or autopsy subjects. The expression of KLF5-, -smooth muscle actin-, and KP-1 (macrophages) -positive cells were counted and compared between groups. Media of control arteries was negative for KLF5. In the luminal layers, KLF5 in unruptured small aneurysm was also negative; KLF5 expression was higher in unruptured large/giant aneurysms than other groups (P<0.05). KP-1 expression in unruptured large/giant aneurysms, ruptured small aneurysms, and ruptured large/giant aneurysms was higher than in unruptured small aneurysms (P<0.05). In the unruptured large/giant aneurysms, KP-1-positive cells were lower than KLF5-positive cells. On the other hand, irrespective of size, KLF5 positivity tended to be lower than KP-1 in the luminal and abluminal layers of all ruptured aneurysms. This represents the first documentation that KLF5 is highly expressed in large and giant unruptured aneurysms and that in ruptured aneurysmal wall KLF5 expression was scarce. These findings suggest that the KLF5 expression and macrophage infiltration play essential roles on aneurysmal growth or rupture.


脳動静脈奇形と遺伝性出血性毛細血管拡張症

脳動静脈奇形と遺伝性出血性毛細血管拡張症


Special Interview 私の病院経営術ー地域に貢献し，地域と共に歩む医療ー


Cyclin-dependent kinase 5 with phosphorylation of tyrosine 15 residue is enriched in striatal matrix compartment in adult mice

Accumulating evidence suggests that the striosome-matrix systems have a tight link with motor and behavioral brain functions and their disorders. Cyclin-dependent kinase 5 (Cdk5) is a versatile protein kinase that plays a role in synaptic functions and cell survival in adult brain, and its kinase activity is stimulated by phosphorylation at tyrosine 15 residue (pY15). In this study, we used an immunohistochemical method to show differential localization of Cdk5-pY15 in the striatal compartments of adult mice, with a heightened density of Cdk5-pY15 labeling in the matrix relative to the striosomes. Our findings indicate that Cdk5-pY15 can be a new marker for the striatal matrix compartment, and suggest a possible involvement of Cdk5-mediated signaling in compartment-specific neurotransmission and disease pathology in the striatum.


Identification and localization of a neuron-specific isoform of TAF1 in rat brain: implications for neuropathology of DYT3 dystonia

The neuron-specific isoform of the TAF1 gene (N-TAF1) is thought to be involved in the pathogenesis of DYT3 dystonia, which leads to progressive neurodegeneration in the striatum. To determine the expression pattern of N-TAF1 transcripts, we developed a specific monoclonal antibody against the N-TAF1 protein. Here we show that in the rat brain, N-TAF1 protein appears as a nuclear protein within subsets of neurons in multiple brain regions. Of particular interest is that in the striatum, the nuclei possessing N-TAF1 protein are largely within medium spiny neurons, and they are distributed preferentially, though not exclusively, in the striosome compartment. The compartmental preference and cell type-selective distribution of N-TAF1 protein in the striatum are strikingly similar to the patterns of neuronal loss in the striatum of DYT3 patients. Our findings suggest that the distribution of N-TAF1 protein could represent a key molecular characteristic contributing to the pattern of striatal degeneration in DYT3 dystonia.


Long-term outcome of severe stroke patients: Is the ADL status at discharge from a stroke center indicative of the long-term outcome?

The objective of this study was to examine the possibility of predicting the long-term outcome of severe stroke patients from the ADL status at discharge. The design is a retrospective observational study in the stroke center at Tokushima University Hospital. Severe stroke patients at discharge with Barthel Index (BI) scores 40 (N=51) were divided into two subgroups retrospectively, improved and unimproved. The Functional Independence Measure (FIM) and BI were analyzed at discharge, 3 and 6 months after onset. Correlation analysis between BI and FIM showed good correlation, especially between BI and motor FIM (mFIM). In conclusion, the ADL status at discharge from a stroke center is not definitely indicative of the long-term outcome, although good recovery of severe stroke cases was observed in males and younger patients, and in patients with motor FIM score>25. This result shows that the first 3 months after the attack should be regarded as an important time window for intensive rehabilitation.

The Journal of Medical Investigation : JMI


Gait and posture assessments of a patient treated with deep brain stimulation in dystonia using three-dimensional motion analysis systems.

Kinesiologic analysis of gait disorders, postural instabilities and abnormal movements is quite difficult to assess objectively by clinical observation, such as by specific scale and video recordings. In this study, we reported one of the aspects of the usefulness of three-dimensional motion analysis (Vicon Systems, Oxford, United Kingdom), which can measure inclusive data of movement disorders and substitute for conventional assessments. A 49-year-old man who had various dystonic symptoms, mainly on his left side of the body, responded well to deep brain stimulation (DBS). The examination quantified how the involuntary movements or other symptoms with dystonia changed before and after treatments.


Exercise intervention soon after stroke patient onset to prevent muscle atrophy


Statins Promote the Growth of Experimentally Induced Cerebral Aneurysms in Estrogen-Deficient Rats

The pathogenesis of cerebral aneurysms is linked to inflammation, degradation of the extracellular matrix, and vascular wall apoptosis. Statins exert pleiotropic effects on the vasculature, independent of their cholesterol-lowering properties. To explore the detailed pathogenesis of cerebral aneurysms, we examined their progression in a rat model and studied whether statins prevent their initiation and growth. Cerebral aneurysms were induced in female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The development of aneurysm was assessed morphologically on corrosion casts. The effects of pravastatin (5, 25, or 50 mg/kg per day) and of simvastatin (5 mg/kg per day) on their aneurysms were studied. Human brain endothelial cells were also used to determine the effects of pravastatin. Pravastatin (5 mg/kg per day) reduced endothelial damage and inhibited aneurysm formation; there was an association with increased endothelial nitric oxide synthase (eNOS) levels and a decrease in human brain endothelial cell adhesion molecules. Unexpectedly, 25 mg/kg per day and 50 mg/kg per day pravastatin and 5 mg/kg per day simvastatin promoted aneurysmal growth, and high-dose pravastatin induced aneurysmal rupture. The deleterious effects exerted by these statins were associated with an increase in apoptotic caspase-3 levels and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, suggesting that statins exert bidirectional effects. Our results provide the first evidence that cerebral aneurysm growth is partly associated with apoptosis and issue a warning that statins exert bidirectional effects on cerebral aneurysms. Additional intensive research is necessary to understand better their mechanisms and to identify patients in whom the administration of statins may elicit deleterious effects.


脳梗塞急性期血管破綻の分子メカニズム

脳梗塞急性期血管破綻の分子メカニズム


Clinical results of boron neutron capture therapy (BNCT) for glioblastoma

The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.


Boron neutron capture therapy combined with fractionated photon irradiation for glioblastoma: A recursive partitioning analysis of BNCT patients

Eight patients to received Boron Neuron Capture Therapy (BNCT) were selected from 33 newly diagnosed glioblastoma patients (NCT(+) group). Serial 42 glioblastoma patients (NCT(-) group) were treated without BNCT. The median OS of the NCT(+) group and NCT (-) group were 24.4 months and 14.9 months. In the high risk patients (RPA class V), the median OS of the NCT(+) group tended to be better than that of NCT(-) group. 50% of BNCT patients were RPA class V.


Activation of estrogen receptor- and of angiotensin-converting enzyme 2 suppresses ischemic brain damage in oophorectomized rats.

Like the angiotensin II type 1 receptor blocker, endogenous estrogen (17-estradiol) is neuroprotective against cerebral ischemia; its effects are thought to be mediated by estrogen receptors (ERs). To verify the role of ERs and the brain renin-angiotensin system in estrogen-deficient rats with ischemia induced by middle cerebral artery occlusion, we compared rats subjected to oophorectomy (OVX(+)) with sham-oophorectomized rats (OVX(-)) and OVX(+) rats treated with 0.3 or 3.0 mg/kg of olmesartan for 2 weeks before middle cerebral artery occlusion. Independent of the blood pressure, the cortical infarct volume was larger in OVX(+) than in OVX(-) rats. It was smaller in olmesartan-pretreated OVX(+) rats. The expression of ER in the peri-infarct region was correlated with the reduction of cortical infarct but not that of ER or G protein-coupled estrogen receptor. Olmesartan prevented ER downregulation in the cortical peri-infarct area, without affecting ER or G protein-coupled estrogen receptor. Olmesartan also increased mRNA expression of angiotensin-converting enzyme 2, Bcl-2, and Bcl-xL and reduced angiotensin II and cleaved caspase 3. These effects were augmented by olmesartan and abolished by the ER inhibitor. In OVX(+) rats treated with the ER agonist alone, the infarct size was decreased, and the neuroprotective genes were upregulated. These findings suggest that the transactivation of neuroprotective genes and the reduction in brain angiotensin II are ER dependent and that this may augment neuroprotection together with an angiotensin II type 1 receptor blockade by olmesartan. We present the new insight that the activation of ER independent of estrogen contributes at least partly to limiting cerebral ischemic damage.


行政的な「高次脳機能障害」の診断

Diagnostic criteria of the administrative higher brain dysfunction are defined. Young people between the period of entering school and starting work occasionally suffer from brain damage. Although the patient may seem to recover, memory and attention disturbances may continue. As a result, higher brain dysfunction may interfere with return to school, and reinstatement is difficult.Patients diagnosed with higher brain dysfunction by these diagnostic criteria can continue rehabilitation and achieve functional restoration. In the Tokushima University Hospital, many patients with cerebrovascular disease, brain tumor, or traffic injury(in that order)consulted about higher brain dysfunction.


小脳血管芽腫と褐色細胞腫を合併したvon Hippel-Lindau病に対する手術の1例


Long-survivors of glioblastoma treated with boron neutron capture therapy (BNCT)

The purpose of this study was to compare the radiation dose between long-survivors and non-long-survivors in patients with glioblatoma (GBM) treated with boron neutron capture therapy (BNCT). Among 23 GBM patients treated with BNCT, there were five patients who survived more than three years after diagnosis. The physical and weighted dose of the minimum gross tumor volume (GTV) of long-survivors was much higher than that of non-long survivors with significant statistical differences.


改正臓器移植法と脳神経外科医

改正臓器移植法と脳神経外科医

The Journal of the Japan Medical Association


福嶌教偉 救急医療・脳神経外科施設からみた脳死下臓器提供の現況と課題

福嶌教偉 救急医療・脳神経外科施設からみた脳死下臓器提供の現況と課題


Bilateral pallidal deep brain stimulation in primary Meige syndrome

Primary Meige syndrome is an idiopathic movement disorder that manifests as craniofacial and often cervical dystonias. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as a powerful surgical option in the treatment of primary generalized or segmental dystonia. However, the experience with GPi-DBS in Meige syndrome is limited. We followed 5 patients with disabling Meige syndrome treated by bilateral GPi-DBS for 49 ± 43.7 (mean ± SD) months. All patients were assessed before surgery and at the last follow-up after surgery using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) which includes both the movement and disability scales. Bilateral GPi-DBS produced a sustained and long-lasting improvement in dystonia symptoms associated with Meige syndrome. At the last follow-up, the mean scores of BFMDRS movement and disability scales improved significantly by 84 ± 6.8% (range, 75-94%) and 89 ± 8.1% (range, 80-100%), respectively. Bilateral pallidal stimulation is a beneficial therapeutic option for long-term relief of the disabling dystonia symptoms in Meige syndrome.


Dural arteriovenous fistulae after cerebral infarction: report of two cases

We first report 2 patients in whom dural arteriovenous fistulae (dAVFs) developed after cerebral infarction. One patient was a 49-year-old man who had a right embolic stroke 6 months after his first ischemic attack. Angiograms showed a de novo left transverse sigmoid sinus dAVF. One year later, shunt flow through the dAVF was increased. The second patient was a 45-year-old woman who presented with right cerebral infarction and moyamoya disease. Three weeks later, she underwent right superficial temporal artery-middle cerebral artery bypass. Ten months after the operation, angiograms showed the development of dAVFs in the left transverse sigmoid sinus and progressive moyamoya disease. We document the first patients with cerebral infarction and progressive moyamoya disease in whom a de novo dAVF developed. Moyamoya disease and dAVF are associated with an increase in dural angiogenic factors, and ischemia induces their increase. This may be the mechanism by which vaso-occlusive ischemia contributes to the formation of de novo dAVFs.


Olfactory type G-protein alpha subunit in striosome-matrix dopamine systems in adult mice

There is a growing body of evidence that striosome-matrix dopamine systems are tightly linked with motor and behavioral brain functions and disorders. In this study, we used an immunohistochemical method to show differential expression of the olfactory type G-protein alpha subunit (Galphaolf) that involves in the coupling of dopamine D1 receptor with adenylyl cyclase in the striatal compartments of adult mice, and observed heightened density of Galphaolf labeling in the striosomes relative to the matrix compartment. Our findings suggest that Galphaolf could be one of the key molecules for controlling differential responses of the striosome and matrix compartments to dopamine D1 receptor signaling in the striatum of adult mice.


Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats.

OBJECTIVE: The formation of cerebral aneurysms is associated with endothelial damage and macrophage migration. Hypothesizing that the opening of tight junctions due to the disappearance of the tight junction proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia allows macrophage migration, leading to cerebral aneurysm formation, we investigated the role of tight junction proteins. METHODS: The vascular wall of female rats subjected to hypertension, oophorectomy (OVX), and hemodynamic stress to induce cerebral aneurysms was evaluated morphologically, immunohistochemically, and by quantitative RT-PCR. We also assessed the regulation of tight junction proteins in human brain endothelial cells (HBECs). RESULTS: In the very early stage before aneurysm formation, the expression of occludin and ZO-1 was reduced in injured endothelial cell junctions exhibiting gaps. In the course of aneurysmal progression their reduction progressed and was correlated with macrophage migration. In hypertension along with OVX rats we observed an increase in angiotensin II and the degradation molecules matrix metalloproteinase-9 (MMP-9), nicotinamide-adenine dinucleotide phosphate oxidases and monocyte chemoattractant protein-1. The mineralocorticoid receptor blocker eplerenone increased occludin and ZO-1 expression; this was associated with a reduction in angiotensin II and the degradation molecules and resulted in the inhibition of macrophage exudation and aneurysm formation. In HBECs, occludin and ZO-1 downregulation by angiotensin II and estrogen deficiency was reversed by eplerenone, the MMP inhibitor SB3CT, and apocynin. Our results suggest that macrophage migration is associated with the reduction in tight junction proteins induced by the degradation molecules. CONCLUSION: In rats, the destruction of tight junctions may facilitate macrophage migration and cerebral-aneurysm formation.


Microsurgical Management of Incomplete Coiled and Recurrent Aneurysms

コイル塞栓術後の脳動脈瘤手術の成績と注意点

We determined microsurgical techniques for treating previously coiled aneurysms and report the outcomes. Twelve symptomatic patients with incomplete or recurrent aneurysms were managed microsurgically. The necks of five incomplete coiled aneurysms were clipped (mean time to microsurgery, 35.5 days), and one was treated with bypass surgery. One of the patients who underwent neck clipping had bleeding during dissection of the aneurysm. Six patients who had recurrent aneurysms underwent microsurgery at a mean of 778 days after initial complete embolization. Two fully recovered from transient ischemic symptoms that occurred after microsurgery and the coil became extruded in one other patient. The necks of the aneurysms were clipped in five of these patients and the aneurysm was wrapped in one. Direct clipping is the preferred microsurgical treatment for coiled aneurysms. The necks of such aneurysms should be carefully clipped according to the timing of the surgery and the status of the aneurysm.

症候性脳動脈瘤に対してコイル塞栓術を施行した後に,日を置いて直達手術(クリッピング術など)を行った12症例について検討した.初回塞栓術で完全閉塞ができなかった群(6例)では,初回塞栓術から平均35.5日で直達手術を行った.1例に術中出血があり,後遺症が出現した.残り4例はコイルを摘出することなくクリッピングを行い,1例はhigh flow bypassを併用して動脈瘤および母血管を閉塞した.初回塞栓術にてほぼ完全に閉塞できた群(6例)では,初回塞栓術より平均778日後に直達手術を施行した.術中の破裂はなく,2例で一過性の脳虚血症状が出現したが,退院時には術前の状態に回復した.コイル塞栓術後に直達手術を行う際は,コイルの閉塞率と手術のタイミングにより手術方法を考慮すべきである.


Change of Platelet Aggregation During the Cessation of Antiplatelet Therapy in Patients with Cerebrovascular Reconstruction Surgery

抗血小板薬中止に伴う血小板凝集能の変化 脳血管障害による手術の場合


Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroked in routine clinical practice (The Japan post-marketing alteplase registration study (J-MARS)

In Japan, alteplase at 0.6 mg/kg was approved in October 2005 for use within 3 hours of stroke onset by the Ministry of Health, Labor and Welfare (MHLW). The aim of the Japan post-Marketing Alteplase Registration Study (J-MARS), which was requested by MHLW at the time of approval, was to assess the safety and efficacy of 0.6 mg/kg alteplase in routine clinical practice for the Japanese. A total of 7492 patients from 942 centers were enrolled in the J-MARS, an open-label, nonrandomized, observational study, from October 2005 to October 2007. Primary outcome measures were symptomatic intracranial hemorrhage (a deterioration in NIHSS score >or=4 from baseline) and favorable outcome (modified Rankin Scale score, 0-1) at 3 months after stroke onset. The proportion of patients with symptomatic intracranial hemorrhage in 7492 patients (safety analysis) was 3.5% (95% confidence interval [CI], 3.1%-3.9%) within 36 hours and 4.4% (95% CI, 3.9%-4.9%) at 3 months. The overall mortality rate was 13.1% (95% CI, 12.4%-13.9%) and the proportion of patients with fatal symptomatic intracranial hemorrhage was 0.9% (95% CI, 0.7%-1.2%). The outcomes at 3 months were available for 4944 patients and the proportion of favorable outcome (efficacy analysis) was 33.1% (95% CI, 31.8%-34.4%). The subgroup analysis in patients between 18 and 80 years with a baseline NIHSS score <25 demonstrated that favorable outcome at 3 months was 39.0% (95% CI, 37.4%-40.6%). These data suggest that 0.6 mg/kg intravenous alteplase within 3 hours of stroke onset could be safe and effective in routine clinical practice for the Japanese.


頸動脈内膜剥離術の適応と手術手技

頸動脈内膜剥離術の適応と手術手技

The Journal of Japanese College of Angiology


Bilateral pallidal stimulation in Meige syndrome

Meige 症候群に対する両側淡蒼球刺激術


[Revised act on organ transplantation from neurosurgeon's viewpoint].

特集: 改正臓器移植法の問題点とその対応 脳神経外科医の立場から

The revised act on organ transplantation was passed in July 2009; it will be implemented in July 2010. This law allows organ donation from a brain-dead person with or without an Organ Donation Decision Card, if the family members permit this donation and the brain-dead person had not decided against it when conscious. In Japan, the legal definition of human death has not changed after the revision of the act on organ transplantation; therefore, brain death is considered human death for the purpose of organ transplantation. Certain minor revisions are required in the medical and legal criteria for diagnosis of brain death, especially for children under 6 years. Ancillary tests, including radioisotope measurement of cerebral blood flow and auditory brainstem evoked potentials, should be considered for younger children or in cases where comprehensive neurological examination was not possible because of injuries to the face, eyes, or ears. An increase in the number of organ donations from brain-dead persons because of the revised act will greatly increase the responsibility of and burden on hospitals and neurosurgeons that treat many emergency cases of severe brain injury and stroke. Adequate socioeconomic and systemic medical support should be provided to hospitals where organ donation is carried out.

Brain and Nerve = Shinkei kenkyū no shinpo

脳と神経 - 神経研究の進歩


Incidence and clinical correlation of intracranial hemorrhages observed by 3-tesla gradient echo T2*-weighted images following intravenous thrombolysis with recombinant tissue plasminogen activator

The purpose of this study was to determine the incidence and clinical correlation of intracranial hemorrhages (ICHs) detected by 3-tesla gradient echo T(2)*-weighted images after intravenous recombinant tissue plasminogen activator (rt-PA) administration. We included 43 consecutive patients with anterior-circulation ischemia who underwent MRI studies before and after thrombolysis. Each hemorrhage was classified as a hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study definition. The clinical outcome was defined as an improvement (> or =4-point reduction) or deterioration (> or =4-point increase) based on a comparison between the initial and the 30-day NIHSS scores. The incidence of ICHs was 58%, and the HI rate was 52%; both were higher than the rates reported in the literature. Most of the patients with HI improved clinically, and these patients had second MRAs that showed recanalization. None of the patients with PH demonstrated improvement. Three-tesla MRI may reveal a higher frequency of HI type hemorrhages than lower-field MRIs, and HI may be a predictor of good recovery by reflecting the presence of recanalization. The rate of PH in our study was low compared to other studies, probably due to the lower dosage of rt-PA.


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