A Novel Approach to Microvascular Decompression for Hemifacial Spasm: Method Description and Associated Outcome

Microvascular decompression (MVD) is the only potential cure for hemifacial spasm (HFS). However, traditional techniques such as the interposition method may have limited effect in some cases. Alternative techniques have been proposed; however, they can be more complex or difficult to perform than the standard approach. To describe a safe decompression technique-the "shelter method"-which involves creating a shelter-like space around the facial nerve root exit zone and present associated outcomes. Medical records and intraoperative findings of 92 patients with HFS who underwent MVD using the shelter method between April 1997 and March 2017 were retrospectively reviewed. As a historical control group, we included 53 patients who had undergone MVD by the traditional interposition method before March 1989. The patients were divided into 3 subgroups according to the arteries involved and degree or direction of arterial compression to the seventh nerve. Patient outcomes were assessed as excellent, good, fair, and poor according to the MVD scoring system of the Japan Society for MVD Surgery. In the shelter method group, complete disappearance of HFS was achieved in 87 patients (94.6%). The curative rate of the shelter method group was significantly higher than that of the interposition method group. The overall complication rates were significantly lower in the shelter method group than in the interposition method group. Our findings indicate high curative and low complication rates of the shelter method, suggesting that it helps treat HFS caused by various types of arterial compression.


「コロナ禍におけるホスピタルアート制作の方法と意義―マスキングテープとフィルムシートの活用―」

『オンラインジャーナル』(アートミーツケア学会)

『オンラインジャーナル』(アートミーツケア学会)


"Further Hospital Art Development of Masking Tape Using Thin Film Sheet"

Asploro Journal of Biomedical and Clinical Case Reports


"Cœur résonant": online hospital art creation with people in the distance

Global Journal of Arts and Social Sciences


[実践報告]ホスピタルアートの普及を目指して-徳島の医療・福祉施設におけるマスキングテープアートの広がり-

『オンラインジャーナル』(アートミーツケア学会)

『オンラインジャーナル』(アートミーツケア学会)


Masking Tape Art-Work May Provide Beneficial Positive Effects

Edelweiss Journal of Biomedical Research and Review


Psychologically comfortable seasonal images for the project on the art in hospitals


Beneficial Art in Hospitals with Masking Tape Initiated from University Hospital


Disequilibrium of Plasma Protease/Anti-Protease Due to Severe Periodontal Disease Contributes to Human Subarachnoid Hemorrhage


Action observation treatment improves gait ability in subacute to convalescent stroke patients.

The aim of this study was to investigate the effects of action observation treatment (AOT) on gait ability in patients with subacute to convalescent stroke. Sixteen patients with subacute stroke were divided into a control group (n = 8) and AOT group (n = 8) when admitted to the convalescent ward. The control group received a conventional rehabilitation only. In addition to conventional rehabilitation, the AOT received AOT for 3 months (30 min per day 5 times per week). The AOT involved observing the action of another subject in a comfortable gait situation from the front, sides, and back via video and conducting the actual action. All participants were assessed during the main-assessment period, which included a baseline (i.e., when admitted to the convalescent ward) and 1, 2, and 3 months after baseline. The sub-assessment period at 2 and 3 months after baseline was conducted with participants who could walk independently. The main outcomes of the main-assessment and sub-assessment periods were Functional Ambulation Classification (FAC) and the 10-m walk test (10MWT), respectively. With respect to the FAC, we used a split plot design analysis of covariance to test the interaction between assessment time and group. There was no significant interaction between assessment time and group in FAC. However, a significant improvement of the 10MWT in the sub-assessment period was observed in the AOT group, but not the control group. Our results indicate that AOT may be an effective therapy for patients with subacute to convalescent stroke who can walk independently.


Importance of Managing the Water-Electrolyte Balance by Delivering the Optimal Minimum Amount of Water and Sodium After Subarachnoid Hemorrhage.

After aneurysmal subarachnoid hemorrhage (aSAH), crystalloid fluids with a relatively high sodium concentration have been used to maintain the cerebral blood flow. However, the prophylactic delivery of water and sodium by intravenous (IV) infusion will not necessarily improve the prognosis of patients after aSAH, and the excessive supply of water and sodium can negatively affect the outcome. We hypothesized that the delivery of an optimal amount of water and sodium separately might improve the outcome after aSAH. We recruited 55 consecutive patients who had undergone clipping or endovascular coil embolization after aSAH. Group 1 (n = 33) received conventional therapy (i.e., prophylactic IV sodium and water [protocol 1]). Group 2 (n = 22) received the optimal amount of water and sodium separately (protocol 2). The median total of water and sodium chloride supplied in group 1 was significantly greater than that supplied in group 2 (P < 0.01). The modified Rankin scale score at discharge was 0-2 in 15 patients (95%) in group 2 and 23 patients (55%) in group 1 (P < 0.001). On multivariate logistic regression analysis, the odds ratio for a discharge modified Rankin scale score of 0-2 or 3-6 was significantly associated with the treatment protocol (P < 0.05) and the net fluid balance on days 4-8 (P < 0.05). The separate delivery of optimal amounts of water and sodium could be a promising therapeutic strategy to improve the prognosis after aSAH.


A Single-center Retrospective Study with 5- and 10-year Follow-up of Carotid Endarterectomy with Patch Graft.

Carotid endarterectomy (CEA) is widely used for cervical artery stenosis. In Japan, primary closure after endarterectomy has been a standard technique. Recently, the patch closure has been shown to be superior to the primary suture for the prevention of restenosis and ipsilateral stroke. This study evaluated the 5- and 10-year outcomes following CEA with patch graft closure in our institution. Between January 2000 and March 2013, 134 patients, who underwent CEA with patch graft closure were investigated in the current retrospective study. Among these patients, 102 CEAs in 97 patients were followed up for 5 years and 66 CEAs in 61 patients were for 10 years after the procedure. Restenosis was defined as >50% recurrent luminal narrowing at the endarterectomy site. In 5 years, symptomatic restenosis exhibited minor stroke in one patient at 58 months after CEA (restenosis rate 1.0%). The ipsilateral minor stroke occurred in three patients including the above case (2.9%). In 10 years, asymptomatic restenosis occurred in three patients in addition to the above symptomatic case (restenosis rate 6.1%), and the ipsilateral minor stroke occurred in four patients (6.1%). Carotid endarterectomy with patch graft exerted a high protective effect from restenosis up to 5 and 10 years in our institution. The number of carotid artery stenting is increasing all over the world but we speculated that the established surgical procedure of patched CEA prevented restenosis and ipsilateral stroke.


Activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons.

The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training.


The risk of hemorrhage in stereotactic biopsy for brain tumors.

Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy. J. Med. Invest. 66 : 314-318, August, 2019.

The Journal of Medical Investigation : JMI


Diagnostic Performance of Arterial Spin Labeling for Grading Nonenhancing Astrocytic Tumors


脳震盪の病態と最近の話題

脳震盪の病態と最近の話題


Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study.

Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients. Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms. Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%. Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed.

Journal of Stroke & Cerebrovascular Diseases


Posttraumatic Cerebrospinal Fluid Leak Associated with an Upper Cervical Meningeal Diverticulum

Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear. We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved. Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak.


スポーツ頭部外傷の基礎知識

スポーツ頭部外傷の基礎知識

The Japanese Journal of Occupational Therapy


Flow Alteration Therapy for Ruptured Vertebral Artery Dissecting Aneurysms Involving the Posterior Inferior Cerebellar Artery

Surgery for- and endovascular treatment of vertebral artery (VA) dissecting aneurysms involving the origin of the posterior inferior cerebellar artery (PICA) remain challenging. Their ideal treatment is complete isolation of the aneurysm by surgical or endovascular trapping plus PICA reconstruction. However, postoperative lower cranial nerve palsy and medullary infarction are potential complications. We report four patients with VA dissecting aneurysms involving the PICA origin who were treated by occipital artery (OA)-PICA bypass followed by proximal occlusion of the VA and clip ligation of the PICA origin instead of trapping. There were no procedural or ischemic complications. In all patients, angiography performed 2-3 weeks later showed good patency of the bypass graft and complete obliteration of the aneurysm. During the follow-up period ranging from 1 to 14 years, none experienced bleeding. Although retrograde blood flow to the dissecting aneurysm persisted in the absence of trapping, iatrogenic lower cranial nerve injury could be avoided. The decrease in aneurysmal flow might elicit spontaneous thrombosis and prevent aneurysmal rerupture. Our technique might be less invasive than aneurysmal trapping and help to prevent rebleeding.


Down-regulation of MDR1 by Ad-DKK3 via Akt/NFB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model

Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.


Coloring Techinique of Magnetic Resonance Angiography for Superficial Temporal Artery to Middle Cerebral Artery Bypass surgery

Superficial temporal artery (STA)-to-middle cerebral artery (MCA) bypass is an established surgical technique for achieving revascularization. It is important to select the proper recipient artery of the MCA. Three-dimensional computed tomographic angiography (3D-CTA) and conventional angiography are useful in the selection process but need contrast agents. The authors have designed a coloring MRA technique that needs no agents to visualize the recipient artery. Retrospective evaluation of the efficacy and limitation for selection of the recipient artery and decision of the place and size of the craniotomy were carried out. The authors performed the coloring MRA before operation since January 2013. Ninety-two patients underwent STA-MCA bypass for atherosclerotic stenosis or occlusion of internal carotid artery (ICA), MCA with reference to the coloring MRA. To evaluate the efficacy of coloring MRA, the control group consisted of 75 patients who underwent STA-MCA bypass between January 2012 to November 2013 with reference to 3D-CTA. The size of craniotomy was retrospectively calculated and compared. Neither additional craniotomy nor wrong selection of the recipient artery was done in either group. There was no significant difference in size between the 2 groups in both single and double bypass. The coloring MRA technique was not inferior to 3D-CTA with respect to the size of craniotomy. This novel technique was found to be very helpful not only for the virtual identification of the proper recipient artery but also for preoperative simulation such as decisions about length of donor artery, location, and size of craniotomy.


Idiopathic and Chronic Epidural Hematoma in the Lumbar Spine: A Case Report and Review of Literatures

Spontaneous and chronic epidural hematoma (SSEH) in the lumbar spine is rare, and idiopathic and chronic SSEH in the lumbar spine is extremely rare disease. Most of lumbar SSEH were acute and secondary with trauma, hematologic disorders, drug, and surgical procedure. Only 20 cases of chronic SSEH in the lumbar spine have been reported and 14 cases among them were considered to be idiopathic. Definitive guidelines for management of this condition are not clear and surgical total evacuation was performed in most of the cases. Some authors reported the epidural bleeding originates in the rupture of Batson's plexus due to a rise in intra-abdominal pressure, but the mechanism is not clearly clarified. We report a surgical case of idiopathic and chronic SSEH. A 61-year-old woman suffered a sudden onset of severe lumbar pain during sleep. She had no history of trauma, spinal surgery, or hypertension. Magnetic resonance imaging revealed a lumbar chronic epidural hematoma which compressed the dural sac behind and extended from L2 to L5. This patient underwent the partial evacuation of the hematoma with partial hemilaminectomy on left at L2/3, resulting in immediate pain relief and resolution of symptoms and almost absorption of the hematoma within 1 week of the procedure. We presented this rare case and reviewed idiopathic and chronic epidural hematoma in the lumbar spine.


The Berlin international consensus meeting on concussion in sport.

The Fifth International Conference on Concussion in Sport was held in Berlin in October 2016. A series of 12 questions and subquestions was developed and the expert panel members were required to perform a systematic review to answer each question. Following presentation at the Berlin meeting of the systematic review, poster abstracts and audience discussion, the summary Consensus Statement was produced. Further, a series of tools for the management of sport-related concussion was developed, including the Sport Concussion Assessment Tool Fifth edition (SCAT5), the Child SCAT5, and the Concussion Recognition Tool Fifth edition. This paper elaborates on this process, the outcomes, and explores the implications for neurosurgeons in the management of sport-related concussion.


Multi-disciplinary approach for dystonia patients by treatment with deep brain stimulation

ジストニアDBS治療における多職種連携


Treatment with the PPAR Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.

Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP) rats. Three weeks later, they were ovariectomized (OVX/GFP rats). We subjected 7-week-old Wistar male and 13-week-old OVX/GFP rats to 90-min cerebral ischemia. Male and OVX/GFP rats were divided into two groups, one was treated with PGZ (2.5 mg/kg/day) and the other served as the vehicle control (VC). In both male and OVX/GFP rats, post-ischemia treatment with PGZ reduced neurological deficits and the infarct volume. In male rats, PGZ decreased the mRNA level of IL-6 and M1-like macrophages after 24 h. In OVX/GFP rats, PGZ augmented the proliferation of resident stem cells in the subventricular zone (SVZ) and the recruitment of GFP stem cells on days 7-14. Both types of proliferated stem cells migrated from the SVZ into the peri-infarct area. There, they differentiated into mature neurons, glia, and blood vessels in association with activated Akt, MAP2, and VEGF. Post-ischemia treatment with PGZ may offer a new avenue for stroke treatment through contribution to neuroprotection and neurogenesis.


Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats.

Estrogen deficiency is thought to be responsible for the higher frequency of aneurysmal subarachnoid hemorrhage in post- than premenopausal women. Estrogen replacement therapy appears to reduce this risk but is associated with significant side effects. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor (ER) modulator with fewer estrogenic side effects, reduces cerebral aneurysm rupture in a new model of ovariectomized rats. Ten-week-old female Sprague-Dawley rats were subjected to ovariectomy, hemodynamic changes, and hypertension to induce aneurysms (ovariectomized aneurysm rats) and treated with vehicle or with 0.3 or 1.0 mg/kg/day bazedoxifene. They were compared with sham-ovariectomized rats subjected to hypertension and hemodynamic changes (HT rats). The vasoprotective effects of bazedoxifene and the mechanisms underlying its efficacy were analyzed. During 12 weeks of observation, the incidence of aneurysm rupture was 52% in ovariectomized rats. With no effect on the blood pressure, treatment with 0.3 or 1.0 mg/kg/day bazedoxifene lowered this rate to 11 and 17%, almost the same as in HT rats (17%). In ovariectomized rats, the mRNA level of ERα, ERβ, and the tissue inhibitor of metalloproteinase-2 was downregulated in the cerebral artery prone to rupture at 5 weeks after aneurysm induction; the mRNA level of interleukin-1β and the matrix metalloproteinase-9 was upregulated. In HT rats, bazedoxifene restored the mRNA level of ERα and ERβ and decreased the level of interleukin-1β and matrix metalloproteinase-9. These findings suggest that bazedoxifene was protective against aneurysmal rupture by alleviating the vascular inflammation and degradation exacerbated by the decrease in ERα and ERβ. Our observation that bazedoxifene decreased the incidence of aneurysmal rupture in ovariectomized rats warrants further studies to validate this response in humans.


パーキンソン病と腰痛脊髄刺激療法適応と課題

パーキンソン病と腰痛脊髄刺激療法適応と課題


MicroRNA-449a deficiency promotes colon carcinogenesis.

MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our analysis found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the numbers and sizes of colon tumors. These effects were associated with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histological scores and was positively correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Additionally, activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.


Remarkable Shrinkage of a Growth Hormone (GH)-secreting Macroadenoma Induced by Somatostatin Analogue Administration: A Case Report and Literature Review.

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.


Risk Factors of Neurological Deterioration in Patients with Cerebral Infarction due to Large Artery Atherosclerosis

In some patients with acute ischemic stroke, neurological deterioration (ND) is observed, and it is difficult to predict at the time of admission. Especially in some patients with large-artery atherosclerosis (LAA), aggressive medical treatments and surgical interventions might be helpful to prevent ND. Therefore, we investigated factors associated with ND in patients with LAA. We studied patients with LAA who were admitted to our hospital. We divided them into 2 groups with (group 1) and without deterioration (group 2), and evaluated their medical records, risk factors, and radiological findings, such as number of diffusion-positive lesion and degree of stenosis. Our study population consisted of 171 patients; 71 (41.5%) did and 100 (58.5%) did not suffer deterioration. By univariate analysis, blood pressure (BP), heart rate, National Institutes of Health Stroke Scale (NIHSS) score, number of diffusion-positive lesion, count of red blood cell, high-density lipoprotein, and degree of stenosis differed significantly between the 2 groups. By multivariate analysis, systolic BP (170 mm Hg, odds ratio: 7.20, P <.001) was associated with ND. Furthermore, number of diffusion-weighted image (DWI)-positive lesion (8), degree of stenosis (>80.0%), and NIHSS score (4) were also independent factors associated with ND. High BP, severity of neurological deficit at the time of admission, and radiological findings, such as degree of stenosis and number of DWI-positive lesion, are independently associated with ND in patients with LAA.

Journal of Stroke & Cerebrovascular Diseases


Design and Synthesis of Novel Anti-metastatic Hypoxic Cytotoxin TX-2137 Targeting AKT Kinase.

The hypoxic microenvironment plays a crucial role in the malignant progression of tumor cells. Moreover, AKT, a serine/threonine kinase, is activated by various extracellular growth factors and is important for cell growth, survival, and motility of leukocytes, fibroblasts, endothelial cells, and tumor cells. Therefore, we aimed to design an anti-metastatic hypoxic cytotoxin which has inhibitory effects on AKT.TX-2137 was designed and synthesized based on the structural similarity of a preexisting AKT1/2 kinase inhibitor and a hypoxic cytotoxin tirapazamine. TX-2137 effectively reduced the expression of phosphorylated AKT and matrix metalloproteinase 9 (MMP9) and showed strong inhibition of the proliferation of B16-F10, HT-1080, and MKN-45 cells. In addition, TX-2137 exhibited hypoxia-selective cytotoxicity towards A549 cells and inhibited liver metastasis of B16-F10 cells in a xenograft chick embryo model in the same way as doxorubicin.TX-2137 may be a potent lead compound in the development of a novel anti-metastatic AKT kinase inhibitor.


Postoperative Hematoma Requiring Recraniotomy in 1149 Consecutive Patients with Intracranial Tumors

The reported 30-day mortality rate after brain tumor surgery is 2.2% to 2.9%, with a postoperative hematoma (POH) as the most frequent cause of death. To investigate the risk factors for a POH requiring a recraniotomy after brain tumor surgery in a large, contemporary, single-institution consecutive series. We included 1149 patients who underwent surgery for intracranial tumors at the Tokushima University Hospital from 1997 to 2014. The patient charts were retrospectively studied from our prospectively collected database. We analyzed the risk factors, type of hemorrhage, time to reoperation, and outcomes. The incidence of a POH requiring a recraniotomy was 2.09%. Among the patients with a POH requiring a recraniotomy, 12.5% died within 30 days of the first surgery. The incidence of a POH requiring a recraniotomy significantly correlated with the incidence of a hemangioblastoma, infratentorial tumors, and a prolonged operative time (>10 h), but not with the patient age or sex, surgical procedure (biopsy or craniotomy), surgical type (primary or secondary), bleeding volume, or intraoperative blood transfusion requirement. A recraniotomy for a POH was performed in 54% of the patients just after the first operation, and within 24 h for 79% of the patients. The clinical status at the time of discharge deteriorated in 52% of the patients. Hemangioblastomas, infratentorial tumors, and an operative time exceeding 10 h were significantly correlated with an increased risk of a POH; these factors were responsible for 12.5% of the 30-day surgical mortality rate.


Consensus statement on concussion in sport - the 5th international conference on concussion in sport held in Berlin, October 2016


Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset - Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients

As the safety and effectiveness of urgent carotid artery stenting (CAS) for neurologically progressing patients remain controversial, we retrospectively analyzed the outcome of urgent CAS based on the patients' pathophysiological condition and neuroimaging findings. We divided 71 patients who underwent CAS within 14 days of stroke onset into two groups. Group 1 (n = 35) was comprised of patients with progressing neurologic signs and a reversible ischemic penumbra on magnetic resonance images (MRI). They were treated by urgent CAS. Group 2 (n = 36) was neurologically stable and underwent prophylactic CAS. In all patients we recorded the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin scale (mRS). Urgent CAS resulted in significant improvement in the NIHSS score, when compared before and after CAS in group 1 (5.3 ± 4.3, P < 0.01). The rate of good outcomes (mRS 0-2 at 3 months post-CAS) was 48.6% in group 1, and 75% in group 2. The cumulative incidence of ipsilateral stroke between 31 days and 1 year was 5.9% in group 1, and 0% in group 2. The procedural complication rate was similar in both groups (group 1: 5.7%, n = 2; group 2: 5.6%, n = 2). No patient suffered a symptomatic intracerebral hemorrhage. When the pathophysiological status and neuroimaging findings are used to determine patient eligibility for urgent CAS, this treatment improve neurologic outcome and can be performed as safely as prophylactic CAS in our cohort of patients with acute ischemic stroke.


Pulsatile Tinnitus due to an Aberrant Internal Carotid Artery in the Middle Ear:A Case Report

中耳内頚動脈走行異常により拍動性耳鳴を生じた1症例


Intra-arterial high signals on arterial spin labeling perfusion images predict the occluded internal carotid artery segment

Arterial spin labeling (ASL) involves perfusion imaging using the inverted magnetization of arterial water. If the arterial arrival times are longer than the post-labeling delay, labeled spins are visible on ASL images as bright, high intra-arterial signals (IASs); such signals were found within occluded vessels of patients with acute ischemic stroke. The identification of the occluded segment in the internal carotid artery (ICA) is crucial for endovascular treatment. We tested our hypothesis that high IASs on ASL images can predict the occluded segment. Our study included 13 patients with acute ICA occlusion who had undergone angiographic and ASL studies within 48 h of onset. We retrospectively identified the high IAS on ASL images and angiograms and recorded the occluded segment and the number of high IAS-positive slices on ASL images. The ICA segments were classified as cervical (C1), petrous (C2), cavernous (C3), and supraclinoid (C4). Of seven patients with intracranial ICA occlusion, five demonstrated high IASs at C1-C2, suggesting that high IASs could identify stagnant flow proximal to the occluded segment. Among six patients with extracranial ICA occlusion, five presented with high IASs at C3-C4, suggesting that signals could identify the collateral flow via the ophthalmic artery. None had high IASs at C1-C2. The mean number of high IAS-positive slices was significantly higher in patients with intra- than extracranial ICA occlusion. High IASs on ASL images can identify slow stagnant and collateral flow through the ophthalmic artery in patients with acute ICA occlusion and help to predict the occlusion site.


Noninfectious prevertebral soft-tissue inflammation and hematoma eliciting swelling after anterior cervical discectomy and fusion.

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) procedures are performed to treat patients with cervical myelopathy or radiculopathy. Dysphagia is a post-ACDF complication. When it coincides with prevertebral space enlargement and inflammation, surgical site infection and pharyngoesophageal perforation must be considered. The association between dysphagia and prevertebral inflammation has not been reported. The authors investigated factors eliciting severe dysphagia and its relationship with prevertebral inflammation in patients who had undergone ACDF. MATERIALS The clinical data of 299 patients who underwent 307 ACDF procedures for cervical radiculopathy or myelopathy at Kushiro Kojinkai Memorial Hospital and Kushiro Neurosurgical Hospital between December 2007 and August 2014 were reviewed. RESULTS After 7 ACDF procedures (2.3%), 7 patients suffered severe prolonged and/or delayed dysphagia and odynophagia that prevented ingestion. In all 7 patients the prevertebral space was enlarged. In 5 (1.6%) the symptom was thought to be associated with prevertebral soft-tissue edema; in all 5 an inflammatory response, hyperthermia, and an increase in the white blood cell count and in C-reactive protein level was observed. After 2 procedures (0.7%), we noted prevertebral hematoma without an inflammatory response. None of the patients who had undergone 307 ACDF procedures manifested pharyngoesophageal perforation or surgical site infection. CONCLUSIONS Severe dysphagia and odynophagia are post-ACDF complications. In most instances they are attributable to prevertebral soft-tissue edema accompanied by inflammatory responses such as fever and an increase in the white blood cell count and in C-reactive protein. In other cases these anomalies are elicited by hematoma not associated with inflammation.


Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma.

Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.


What strategies can be used to effectively reduce the risk of concussion in sport?

To examine the effectiveness of concussion prevention strategies in reducing concussion risk in sport. Systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Eleven electronic databases searched and hand-search of references from selected studies. The following were the study inclusion criteria: (1) contained original human research data; (2) investigated an outcome of concussion or head impact; (3) evaluated a concussion prevention intervention; (4) included sport participants; (5) analytical study designand (6) peer-reviewed. The following were the exclusion criteria: (1) review articles, case series or case studies and (2) not in English. The studies selected (n=48) provided evidence related to protective gear (helmets, headgear, mouthguards) (n=25), policy and rule changes (n=13) and other interventions (training, education, facilities) (n=10). Meta-analyses demonstrate a combined effect of a 70% reduction (incidence rate ratio (IRR)=0.3 (95% CI: 0.22 to 0.41)) in concussion risk in youth ice hockey leagues where policy disallows body checking, and the point estimate (IRR=0.8 (95% CI: 0.6 to 1.1)) suggests a protective effect of mouthguards in contact and collision sport (basketball, ice hockey, rugby). Highlights include a protective effect of helmets in skiing/snowboarding and the effectiveness of policy eliminating body checking in youth ice hockey. Future research should examine mouthguards in contact sport, football helmet padding, helmet fit in collision sport, policy limiting contact practice in youth football, rule enforcement to reduce head contact in ice hockey and soccer, ice surface size and board/glass flexibility in ice hockey and training strategies targeting intrinsic risk factors (eg, visual training). PROSPERO 2016:CRD42016039162.


The Current Status of Microvascular Decompression for the Treatment of Hemifacial Spasm in Japan: An Analysis of 2907 Patients Using the Japanese Diagnosis Procedure Combination Database

Microvascular decompression (MVD) is widely used as a safe and effective treatment for hemifacial spasm (HFS). However, the extent of application of this therapeutic method and its outcomes in Japan are currently unclear. To address these questions, we analyzed the utilization of MVD for the treatment of HFS during the 33- month period from July 2010 to March 2013. We conducted an analysis on data contained in the Diagnosis Procedure Combination database in Japan. This analysis showed that MVD was used for the treatment of HFS in 2907 cases (men, 916; women, 1991) with 2.2 times more women treated than men. MVD for HFS was most frequently performed in women aged 50 to 69 years; however, most men were aged between 40 and 59 years at the time of the procedure. The numbers of procedures performed per 100,000 population/year were 0.83 overall in Japan, with the numbers larger in prefectures with larger populations. Regarding discharge outcomes, the mortality rate was 0.1%. The mean length of hospital stay in patients undergoing MVD for HFS was 14.7 days. This analysis provides preliminary information regarding the trends in the performance of MVD for the treatment of HFS in Japan. Further studies on other registries that contain data obtained by standardized assessment methods and that include long-term outcomes and postoperative complications are required.


Tissue type plasminogen activator and edaravone combination therapy: YAMATO study

We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.


Usefulness of 3-Tesla magnetic resonance arterial spin-labeled imaging for diagnosis of cranial dural arteriovenous fistula

Conventional digital subtraction angiography (DSA) has been a useful tool for the diagnosis of cranial dural arteriovenous fistula (cDAVF). In most patients with cDAVF, blood flow through the arteriovenous shunt was pooled at diseased veins and/or sinuses. Therefore, we speculated that pooled blood at diseased veins in patients with cDAVF could be detected on arterial spin-labeled imaging (ASL). The purpose of the present study was to investigate the usefulness of ASL to detect cDAVF. Consecutive 13 patients with cDAVF who were admitted to our hospital between April 2013 and September 2016 were included in our study. We performed magnetic resonance imaging (MRI), including ASL, before DSA and within 7days after treatment for all of our patients. The accuracy for diagnosis of cDAVF was compared between conventional MRI findings and ASL findings. We also investigated the difference in ASL findings before and after treatment. We could detect venous ASL signals in 12 patients, and this was more sensitive for diagnosis of cDAVF versus conventional MRI findings. ASL found the same location of cDAVF as conventional angiography. After successful treatment, venous ASL signals disappeared. ASL might be useful to detect cDAVF and predict the location of diseased sinuses.


Bone scintigraphy for the diagnosis of the responsible level of osteoporotic vertebral compression fractures in percutaneous balloon kyphoplasty

This study was to investigate the efficacy of bone scintigraphy in order to diagnose the correct level of vertebral compression fractures (VCF) for the severe back pain before balloon kyphoplasty (BKP) was performed. A total of 30 consecutive patients were treated with BKP for 38 times since May 2012. Eleven patients had acute multi-level VCFs. Bone scintigraphy was performed preoperatively except for the first case and the case with a chronic course and the level responsible for the pain was defined with bone scintigraphy. The responsible level of acute single level VCF was easily diagnosed with T1, T2, and fat sat T2 but the responsible level of acute multi-level VCFs was not easily determined. BKP was performed at the most accumulated level on bone scintigraphy and the preoperative and postoperative Visual analogue score (VAS) scores were researched with questionnaire postoperatively. BKP was effective in relief of pain at the most accumulated level on bone scintigraphy. Preoperative VAS score (average 8.6) was significantly improved at post-ope day1 (average 3.9), at discharge (average 2.4) and at 1 month after discharge (average 2.1). New symptomatic VCFs after the first treatment occurred in 5 patients at an adjacent level in 3 and twice in 2 of 5 and additional BKP was effective in each patient. The correct level of symptomatic VCF in the patients with acute multi-level VCFs should be diagnosed to achieve good clinical results. In this study, we showed that bone scintigraphy is very useful in diagnosing the proper level for BKP in addition to CT and MRI.


Optimal Timing of Diffusion-Weighted Imaging to Avoid False-Negative Findings in Patients With Transient Ischemic Attack

We aimed to investigate the optimal timing of diffusion-weighted imaging (DWI) in patients with transient ischemic attack (TIA). Seventy-three consecutive patients with TIA underwent DWI on admission (initial DWI) and at 24 hours after admission (second DWI). Patients were divided into 2 groups based on initial DWI findings in relation to the second examination: false negative (group 1) and other (group 2). The probability of initial false-negative findings was determined for each hour from TIA onset to initial DWI. Multivariate analysis was used to evaluate the independent risk factors associated with false-negative findings on initial DWI. Of the 73 patients examined (56 men; mean age, 68 years), 9 (12%) were categorized into group 1. The latency from TIA onset to initial DWI was 1.7±0.6 hours for group 1 (range, 1-2.8 hours) and 3.3±2.6 hours for group 2 (range, 35 minutes to 12 hours). The probability of false-negative findings on initial DWI decreased in a time-dependent manner (25%, 21%, and 7% for 1, 2, and 3 hours, respectively), and no false-negative findings were observed on initial DWI performed at >3 hours from symptom onset. Short latency (2 hours) from TIA onset to initial DWI was an independent risk factor related to false-negative findings (odds ratio, 13.11; 95% confidence interval, 1.07-161.38; P=0.045). If the duration between TIA symptom onset and initial DWI is <2 hours, a repeat examination should be performed to minimize the risk of false-positive findings.


Cryptic Recanalization of Chronic Vertebral Artery Occlusion by Head Rotation

Journal of Stroke & Cerebrovascular Diseases


Coexistence of Quasi-moyamoya Disease and POEMS Syndrome in a Patient with Intracranial Hemorrhage: A Case Report and Literature Review

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare paraneoplastic syndrome elicited by plasma cell dyscrasia. Its clinical manifestations are multiple and stroke is not a recognized feature. A 44-year-old woman with a 3-month history of bilateral lower extremity sensorimotor disturbance was admitted to our hospital. Examinations revealed polyneuropathy, organomegaly, hypothyroidism, monoclonal gammopathy, pelvic plasmacytoma, and elevated serum vascular endothelial growth factor (VEGF) levels. A diagnosis of POEMS was made. Her condition was improved by radiation therapy of her pelvic plasmacytoma and she continued to be seen on an outpatient basis. Five years after her first admission she was re-admitted with sudden-onset right hemiparesis. A brain computed tomography (CT) scan revealed a left intracranial hemorrhage and magnetic resonance (MR) angiography and cerebral angiography showed occlusion of the proximal portion of the bilateral middle cerebral artery and narrowing of the bilateral internal carotid artery at the terminal portion; moyamoya vessels were seen. This is the first report of a patient whose intracranial hemorrhage was attributable to quasi-moyamoya disease associated with POEMS syndrome. We suggest that the POEMS syndrome be ruled out in the differential diagnosis of patients presenting with atypical stroke, multivessel stenotic lesions (moyamoya vessels), and polyneuropathy.


Usefulness of a novel higher brain dysfunction screening test for evaluating higher brain function in healthy persons.

To accurately and rapidly screen for higher brain dysfunction, we developed a screening test named the "higher brain dysfunction screening test" (HIBRID-ST). Previous studies have reported a decrease in higher brain function with age. However, whether HIBRID-ST can detect a decrease in higher brain function in healthy persons remains unclear. We aimed to assess the usefulness of HIBRID-ST for evaluating higher brain function in healthy persons. We recruited 60 persons without physiological abnormalities and divided them into six equal groups based on their age (20s-70s). HIBRID-ST addresses orientation, short-term memory, word recall, situational awareness, visual short-term memory, and graphic replication and includes the Trail Making and Kana-hiroi tests. There was a significant negative correlation between the participants' age and their total HIBRID-ST score (ϱ = -0.68, p < 0.01). The total HIBRID-ST score of participants in their 70s was significantly lower than that of participants in their 20s-60s; the total HIBRID-ST score of participants in their 60s was significantly lower than that of participants in their 20s-50s. Our findings show that HIBRID-ST accurately detects an age-related decline in higher brain function. Further studies are needed to examine the usefulness of HIBRID-ST in patients with higher brain dysfunction. J. Med. Invest. 64: 280-285, August, 2017.

The Journal of Medical Investigation : JMI


Differences In High-Intensity Signal Volume Between Arterial Spin Labeling And Contrast-Enhanced T1-Weighted Imaging May Be Useful For Differentiating Glioblastoma From Brain Metastasis

To determine whether differences in tumor volume between arterial spin labeling (ASL) and contrast-enhanced T1-weighted MR images (CE+T1WI) can help differentiate glioblastoma (GBM) from brain metastasis. Patients with a diagnosis of GBM (n=25) or brain metastasis (n=13) were examined by both conventional and ASL MR imaging. Volumes of interest with high signal intensity on ASL and CE+T1WI were defined using three dimensional analysis software. Tumor volume difference (ASL-CE) and tumor volume ratio (ASL/CE) were obtained. Absolute maximal tumor blood flow (TBF) and TBF ratio (normalized to white matter) were also measured. The Mann-Whitney U test and receiver operating characteristic curve analysis were performed to compare measurements between the tumor groups. Both tumor volume difference and tumor volume ratio were significantly higher in GBM than in metastasis. Both TBF and TBF ratio were higher for GBM than for metastasis, but the differences were not significant. The difference in tumor volume as measured by ASL high signal intensity and CE+T1WI might be useful for differentiating GBM from metastasis, whereas ASL-derived TBF is insufficient. J. Med. Invest. 64: 58-63, February, 2017.


ジストニアに対する脳深部刺激療法:淡蒼球刺激と視床刺激の併用

ジストニアに対する脳深部刺激療法:淡蒼球刺激と視床刺激の併用


Therapeutic Perspective on Tardive Syndrome with Special Reference to Deep Brain Stimulation

Tardive syndrome (TDS) is a potentially permanent and irreversible hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Guidelines published by the American Academy of Neurology recommend pharmacological first-line treatment for TDS with clonazepam (level B), ginkgo biloba (level B), amantadine (level C), and tetrabenazine (level C). Recently, a class II study provided level C evidence for use of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with TDS. Although the precise pathogenesis of TDS remains to be elucidated, the beneficial effects of GPi-DBS in patients with TDS suggest that the disease may be a basal ganglia disorder. In addition to recent advances in understanding the pathophysiology of TDS, this article introduces the current use of DBS in the treatment of medically intractable TDS.


In-hospital ischemic stroke at Tokushima University Hospital

徳島大学病院脳卒中センターにおける院内発症脳卒中の検討

We assessed the current status of patients with acute in-hospital stroke. 63 patients with acute in-hospital stroke were enrolled. The most prevalent subtype of stroke was embolism(n＝24). The main cause of hospitalization were malignant neoplasms in15. Only 5 patients were treated with rt-PA, 8 patients received endovascular interventions. In-hospital stroke is a sever complication of in-patients and is associated with an unfavorable prognosis, but endovascular interventions offer safe and feasible therapeutic treatment options.


Congenital craniopharyngioma treated by radical surgery: case report and review of the literature

Craniopharyngiomas are 5-10 % of all pediatric tumors, but are seldomly encountered in the perinatal period. Only seven instances of a truly antenatal diagnosis of a congenital craniopharyngioma that subsequently underwent radical surgery have been reported. We present the case of a patient who received the diagnosis of a suprasellar tumor during the prenatal period and received radical surgery. We report a case of a neonatal craniopharyngioma treated surgically. The pregnancy progressed uneventfully until a routine ultrasound at 37 weeks of gestation showed a 15 × 15 mm high echoic mass in the center of the fetal head. Neonatal Gd-enhanced T1-weighted MRI at 5 days of life showed a homogenously enhanced mass (16×22×15 mm) in the sellar and suprasellar lesion. As the tumor showed rapid growth at the 3rd month of life, the patient underwent a surgical treatment and the mass was totally removed. Three years later, the physical and mental development of the patient was normal, and Gd-MRI studies showed no tumor recurrence. The present case is the eighth case of a truly antenatal diagnosis of a craniopharyngioma that underwent successful radical surgery. Craniopharyngioma is a benign tumor and thought to be a slow growing tumor in childhood. The results of radical surgery were very poor, and the mortality and morbidity rates were high in the previous reports due to the huge size of tumor at operation. The present case demonstrated the rapid growth in short interval of Gd-MRI. This is the first report of tumor kinetics of congenital craniopharyngioma with previous reports. The calculated tumor doubling time in our case was 37 days.


Incidence, predictors, and etiology of subsequent ischemic stroke within one year after transient ischemic attack

Background Incidence and predictors of ischemic stroke in patients with transient ischemic attack (TIA) have not been fully clarified outside Europe and North America. Aims We undertook the present prospective, multicenter study to clarify the incidence, predictors, and etiology of ischemic stroke within one year of TIA onset in Japan. Methods The study subjects were patients within seven days of TIA onset who were enrolled in a prospective register from 57 hospitals between June 2011 and December 2013. The primary endpoint was occurrence of ischemic stroke. Results Of 1365 consecutive patients, 1245 were followed for one year after TIA onset; 101 (8.1%) experienced ischemic stroke during follow-up. The leading subtype of ischemic stroke was small-vessel occlusion (SVO) followed by large-artery atherosclerosis (LAA) attributable to intracranial artery diseases. When dividing ischemic stroke events between those occurring within the first 90 days after TIA onset and those occurring after the first 90 days, the leading subtype of ischemic stroke within the first 90 days after TIA onset was SVO, followed by LAA attributable to intracranial artery diseases. In comparison, the subtypes most commonly seen beyond the first 90 days after TIA onset were cardioembolic and LAA attributable to intracranial artery disease. The one-year risk of ischemic stroke increased significantly as ABCD(2) score increased, at 6.2% for 0-3 points, 7.2% for 4-5 points, and 11.6% for 6-7 points. Conclusions The one-year ischemic stroke risk after TIA was about 8% and was associated with the ABCD(2) score. The most common subtype of subsequent ischemic stroke was SVO.


Correlation of 3D Arterial Spin Labeling and Multi-Parametric Dynamic Susceptibility Contrast Perfusion MRI in Brain Tumors.

Arterial spin labeling (ASL) is an alternative method to Dynamic susceptibility contrast (DSC) perfusion MRI for brain tumors. However, ASL cerebral blood flow (CBF) can be easily affected by transit time. DSC MRI derived time to maximum of the residue function (Tmax) is possible to assess the transit time on ASL. Thirty patients with brain tumors were studied using ASL and DSC MRI. The relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), Tmax, and mean transit time (MTT) were obtained from DSC MRI. The ratios of the parameters were analyzed. ASL CBF ratio correlated with the DSC rCBF ratio (r=0.78, p<0.001) and rCBV ratio (r=0.74, p<0.001). There was a moderate correlation between ASL CBF ratio and Tmax ratio (r=-0.43, p<0.05) in brain tumors. ASL CBF strongly correlated with DSC rCBF and rCBV. In addition, a negative correlation was found between ASL CBF and Tmax in brain tumors, indicating that these parameters would be affected by transit time. This may explain why ASL CBF is different from DSC rCBF and rCBV. The decreased DSC Tmax value may suggest high vascularity in a tumor. J. Med. Invest. 63: 175-181, August, 2016.


【高次脳機能障害】 外傷と高次脳機能障害

【高次脳機能障害】 外傷と高次脳機能障害

The Journal of the Japan Medical Association


"Drip and Ship" Cases of Intravenous rt-PA Therapy Transported to stroke Care Unit

徳島大学病院脳卒中センターに搬送されたrt-PA静注療法の"Drip and Ship"症例における検討

Recently,"Drip and Ship"treatment conducted in collaboration of a hospital in remote area and an institution capable of emergency stroke treatment under guidance by a stroke specialist has been reported to be effective. "Drip and Ship" treatment refers to initiating intravenous recombinant tissue-type plasminogen activator(rt-PA)infusion at a remote hospital(Drip)and then transporting patients to an institution capable of multimodality management and endovascular treatment of stroke(Ship). We report here a case analysis and examinations on treatment methods, prognosis, and some other parameters in 16 patients who were transported to the Stroke Care Unit(SCU)of the Tokushima University Hospital while undergoing"Drip and Ship"treatment between June 2013 and November 2015. Occluded vessels were recanalized by rt-PA administration in 5/12patients (42%). For 6 cases in which recanalization was not achieved with rt-PA, endovascular treatment was performed, and recanalization was obtained in 3 patients(50%). There was a marked improvement(8 4points on average)in NIHSS at the time of discharge compared to that before rt-PA administration. A representative case showed a 26-point improvement in NIHSS at the time of discharge compared to the pretreatment value. The advantage of"Drip and Ship"treatment is two-fold : It allows for rt-PA treatment of acute ischemic stroke patients at remote-area institutions incapable of multimodality stroke management, and also makes it possible to add endovascular treatment for rt-PA-irresponsive cases in which recanalization of occluded vessels could not be achieved with rt-PA therapy. The results suggest that the"Drip and Ship"treatment is a safe and effective means to eliminate regional disparities in intravenous rt-PA therapy and can make more contributions to the collaborative stroke care in the Tokushima prefecture in the future.


Successful emergency carotid endarterectomy after thrombolysis with intravenous recombinant tissue-type plasminogen activator

Acute internal carotid artery (ICA) occlusion may result in severe disability or death. Revascularization by carotid artery stenting after treatment with intravenous (iv) recombinant tissue-type plasminogen activator (rt-PA) has been documented. However, there are few reports on emergency carotid endarterectomy (CEA) within 24 hours after the iv administration of rt-PA. We treated a 58-year-old man with right ICA occlusion with iv rt-PA. Although partial recanalization of the ICA was obtained, severe stenosis at the origin of the ICA persisted and he developed fluctuating neurological deficits. To prevent progressive stroke he underwent CEA 10.5 hours after rt-PA treatment. Thereafter his blood pressure was strictly controlled under sedation. During and after CEA there were no hemorrhagic complications. Our findings suggest that emergency CEA may be an option to address symptomatic severe residual ICA stenosis even after iv rt-PA therapy delivered in the acute stage. J. Med. Invest. 63: 300-304, August, 2016.

The Journal of Medical Investigation : JMI


Histopathological Findings in Brains of Patients Who Died in the Acute Stage of Poor-grade Subarachnoid Hemorrhage.

Patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) are likely to die due to irreversible acute-stage primary brain damage. However, the mechanism(s) and pathology responsible for their high mortality rate remain unclear. We report our findings on the brains of individuals who died in the acute stage of SAH. An autopsy was performed on the brains of 11 SAH patients (World Federation of Neurosurgical Societies grade 5) who died within 3 days of admission and who did not receive respiratory assistance. All brains were free of intracranial hematoma and hydrocephalus; all harbored ruptured aneurysms. In all brains, multiple infarcts with perifocal edema were scattered throughout the cortex and subcortical white matter of the whole brain. Infarcts with a patchy - were more often seen than infarcts with a wedge-shaped pattern. Microscopic examination revealed multiple areas with cytotoxic edema and neuronal death indicative of acute ischemic changes. Edema and congestion were more obvious in areas where the subarachnoid clot tightly adhered to the pia mater. Pathologically, the brains of deceased patients with acute poor-grade SAH were characterized by edema and multifocal infarcts spread throughout the whole brain; they were thought to be attributable to venous ischemia. Diffuse disturbance in venous drainage attributable to an abrupt increase in the intracranial pressure and focal disturbances due to tight adhesion of the subarachnoid clot to the pia mater, may contribute strongly to irreversible brain damage in the acute stage of SAH.


Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats

Hyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear. Thirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries. They were divided into two groups and methionine (MET) was or was not added to their drinking water. In another set of experiments, the role of folic acid (FA) against cerebral aneurysms was assessed. During a 12-week observation period, subarachnoid hemorrhage due to aneurysm rupture was observed at the anterior communicating artery (AcomA) or the posterior half of the circle of Willis. HHcy induced by excessive MET intake significantly increased the incidence of ruptured aneurysms at 6-8 weeks. At the AcomA of rats treated with MET, we observed the promotion of aneurysmal growth and infiltration by M1 macrophages. Furthermore, the mRNA level of MMP-9, the ratio of MMP-9 to the tissue inhibitor of metalloproteinase-2, and the level of interleukin-6 were higher in these rats. Treatment with FA abolished the effect of MET, suggesting that the inflammatory response and vascular degradation at the AcomA is attributable to HHcy due to excessive MET intake. We first demonstrate that in hypertensive ovariectomized rats, HHcy induced by excessive MET intake may be associated with the propensity of the aneurysm wall to rupture.


Trigeminal neuralgia caused by fibrous bands: case illustration


Comparison of brain tumor contrast-enhancement on T1-CUBE and 3D-SPGR images

T1-Cube (GE HealthCare) is a relatively new 3-dimensional (3D) fast spin-echo (FSE)-based magnetic resonance (MR) imaging sequence that uses a variable flip angle to acquire gap-free volume scans. We compared the gadolinium enhancement characteristics of a heterogeneous population of brain tumors imaged by T1-Cube and then 3D fast spoiled gradient recall acquisition in steady state (3D FSPGR) 3-tesla MR imaging to identify the superior modality for specific diagnostic purposes. We examined 61 lesions from 32 patients using the 2 sequences after administration of gadopentetic acid (Gd-DTPA; 0.1 mmol/kg). Two neuroradiologists independently measured each lesion twice using a region-of-interest (ROI) method. We measured the contrast-to-noise ratio (CNR), the difference in signal intensity (SI) between the tumor and normal white matter relative to the standard deviation (SD) of the SI within the lesion, for both post-contrast 3D FSPGR and post-contrast T1-Cube images of the same tumor and compared modality-specific CNRs for all tumors and in subgroups defined by tumor size, enhancement ratio, and histopathology. The mean CNR was significantly higher on T1-Cube images than 3D FSPGR images for the total tumor population (1.85 ± 0.97 versus 1.12 ± 1.05, P < 0.01) and the histologic types, i.e., metastasis (P < 0.01) and lymphoma (P < 0.05). The difference in CNR was even larger for smaller tumors in the metastatic group (4.95 to 23.5 mm(2)) (P < 0.01). In contrast, mean CNRs did not differ between modalities for high grade glioma and meningioma. Gadolinium enhancement of brain tumors was generally higher when imaged by T1-Cube than 3D FSPGR, and T1-Cube with Gd enhancement may be superior to 3D FSPGR for detecting smaller metastatic tumors.


Drip-and-ship thrombolytic therapy Supported by the telestroke system for acute ischemic stroke patients living in medically under-served Areas.

There are a few stroke specialists in medically under-served areas in Japan. Consequently, in remote area patients may not receive thrombolysis with intravenous recombinant tissue plasminogen activator (iv rt-PA), the standard treatment for acute ischemic stroke. Using a mobile telestroke support system (TSS) that accesses the internet via a smart phone, we implemented iv rt-PA infusion therapy under a drip-and-ship protocol to treat the stroke patients in medically under-served areas. The physicians at the Tokushima Prefectural Kaifu Hospital (TPKH), located in rural Japan, can relay CT or MRI scans and other patient data via their smart phone to off-site stroke specialists. In the course of 34 months, we used the TSS in 321 emergencies. A total of 9 of 188 (4.8%) with acute ischemic stroke, received iv rt-PA infusion therapy using a mobile TSS; in 5 among these (55.6%), we obtained partial or complete recanalization of occluded arteries. None suffered post-treatment hemorrhage and their average NIH stroke score fell from 14.6 at the time of admission to 6.8 at 24 h post-infusion. The drip-and-ship protocol contributed to the safe and effective treatment of the stroke patients living in medically under-served rural areas.


Noninvasive quantitative tissue characterization of carotid plaque using color-coded mapping based on ultrasound integrated backscatter.


We review current topics in sport-related head injuries including acute subdural hematoma (ASDH), traumatic cerebrovascular disease, cerebral 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 and Japanese judo. Rotational acceleration can cause either cerebral concussion or ASDH due to rupture of a parasagittal bridging vein. Although rare, approximately 80% of patients with cerebral infarction due to sport participation are diagnosed with ischemia or infarction due to arterial dissection. Computed tomography angiography, magnetic resonance angiography, and ultrasound are useful for diagnosing arterial dissection; ultrasound is particularly useful for detecting dissection of the common and internal carotid arteries. Repeated sports head injuries increase the risks of future concussion, cerebral swelling, ASDH, and CTE. To avoid fatal consequences of CTE, it is essential to understand the criteria for safe post-concussion sports participation. Once diagnosed with a concussion, an athlete should not be allowed to return to play on the same day and should not resume sports before the concussion symptoms have completely resolved. Information about the risks and management of head injuries in different sports should be widely disseminated in educational institutions and by sport organization public relations campaigns.


Primary Pulmonary Synovial Sarcoma Showing a Prolonged Survival with Multimodality Therapy

A 54-year-old man was referred to our hospital due to a mass shadow noted on a chest X-ray. Thoracoscopic lobectomy yielded a diagnosis of primary pulmonary synovial sarcoma according to the histology and SYT-SSX1 gene analyses. Five months after the thoracic surgery, he developed brain metastasis; therefore, we performed resection of the brain metastatic focus followed by radiotherapy. As a local recurrence in the thoracic cavity concurrently emerged, systemic chemotherapy was also administered. These observations indicated that a multidisciplinary approach may be useful against primary pulmonary synovial sarcoma, although there is presently no established therapeutic strategy due to its rarity and highly aggressive nature.


腰椎ドレナージを併用した開頭術後に続発性脳脊髄液漏出症を合併した1例,

腰椎ドレナージを併用した開頭術後に続発性脳脊髄液漏出症を合併した1例,


硬膜動静脈瘻の病態把握(判断)と治療(行動)

硬膜動静脈瘻の病態把握(判断)と治療(行動)


Site-specific elevation of interleukin-1β and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model

The pathogenesis of subarachnoid hemorrhage remains unclear. No models of cerebral aneurysms elicited solely by surgical procedures and diet have been established. Elsewhere we reported that only few rats in our original rat aneurysm model manifested rupture at the anterior and posterior Willis circle and that many harbored unruptured aneurysms at the anterior cerebral artery-olfactory artery bifurcation. This suggests that rupture was site-specific. To test our hypothesis that a site-specific response to hemodynamic changes is associated with aneurysmal rupture, we modified our original aneurysm model by altering the hemodynamics. During 90-day observation, the incidence of ruptured aneurysms at the anterior and posterior Willis circle was significantly increased and the high incidence of unruptured aneurysms at the anterior cerebral artery-olfactory artery persisted. This phenomenon was associated with an increase in the blood flow volume. Notably, the level of matrix metalloproteinase-9 associated with interleukin-1β was augmented by the increase in the blood flow volume, suggesting that these molecules exacerbated the vulnerability of the aneurysmal wall. The current study first demonstrates that a site-specific increase in interleukin-1β and matrix metalloproteinase-9 elicited by hemodynamic changes is associated with rupture. Our novel rat model of rupture may help to develop pharmaceutical approaches to prevent rupture.

Journal of Cerebral Blood Flow and Metabolism


小児の全身性ジストニアに対し脳深部刺激術を施行した1例

小児の全身性ジストニアに対し脳深部刺激術を施行した1例


スポーツにおける脳振盪に関する共同声明 ー第4回国際スポーツ脳振盪会議ー【開設と翻訳】


Nuclear factor kappa b is under the control of dopamine signaling in the mouse striatum


The susceptibility vessel sign containing two compositions on 3-tesla T2*-weighted image and single corticosubcortical infarct on diffusion-weighted image are associated with cardioembolic stroke

Although accurate diagnosis of the ischemic stroke subtype is one of the most important factors for selection of therapeutic approach, it is sometimes difficult at the time of admission. We previously reported that susceptibility vessel sign (SVS) with two layers (termed two-layered SVS) on 3-tesla-T2*-weighted image (T2*-WI) might be useful to predict cardioembolic stroke in patients with cerebral major vessel occlusion. We studied about biomarkers on magnetic resonance imaging (MRI), including two-layered SVS for diagnosing cardioembolic stroke. We included 132 ischemic stroke patients within 24h from onset who suffered internal carotid artery or middle cerebral artery occlusion due to cardioembolic stroke (group CE) or large artery atherosclerosis (group LAA). We studied about biomarkers on MRI such as two-layered SVS and abnormal finding patterns of diffusion-weighted image (DWI) for diagnosis of cardioembolic stroke in addition to laboratory data, physiological examination, and clinical findings. In this study, 132 patients (72 men and 60 women, age 74.5 ± 12.1 years) were included. Of these, 63 (47.7%) were cardioembolic stroke. In univariate analysis, frequency of comorbid atrial fibrillation, presence of two-layered SVS on T2*-WI and that of single corticosubcortical infarct on DWI, intima-media thickness were significantly higher in group CE. In multivariate analysis, the presence of two-layered SVS and single corticosubcortical infarct were associated with cardioembolic stroke (odds ratio, two-layered SVS, 30.08, p<0.001; single corticosubcortical infarct, 15.78, p<0.001). Biomarkers associated with cardioembolic stroke may be two-layered SVS on T2*-WI and single corticosubcortical infarct on DWI.


Predictors of a favorable outcome after recanalization in patients with cerebral major vessel occlusion

Although tissue plasminogen activator and endovascular treatment were reported to be useful for recanalization in patients with major vessel occlusion (MVO), the outcome in some patients with recanalization was unfavorable. We could detect prolongation of the ipsilateral posterior cerebral artery (PCA) to the ischemic side on magnetic resonance angiography in some patients (ipsilateral-PCA sign). We investigated the predictors including radiological findings for a favorable outcome after successful recanalization. We included 76 patients with MVO of the anterior circulation and documented recanalization by treatment. We divided our patients into 2 groups: group F (modified Rankin scale [mRS] score = 0-2) and group UF (mRS score = 3-6). We compared biomarkers between the groups. National Institutes of Health Stroke Scale (NIHSS) score before treatment in group F (8.5) was lower than that in group UF (16.0; P <.001). Sensitivity of the ipsilateral-PCA sign was commonly associated with group F (67.5% versus 19.4%, P <.001), and specificity of the sign was 80.6%. Absence of infarcts in the anterior cerebral artery (ACA) territory and ACA occlusion were also associated with a favorable outcome. In multivariate analysis, the ipsilateral-PCA sign and NIHSS score (≤ 10) were independent predictors of favorable outcome (odds ratio = 9.92, 95% confidence interval [CI] 2.71-36.23, P = .001; and odds ratio = 9.15, 95% CI 2.44-34.36, P = .001, respectively) The ipsilateral-PCA sign and low NIHSS score (≤ 10) were predictors of a favorable outcome in patients with MVO and documented recanalization by treatments.

Journal of Stroke & Cerebrovascular Diseases


Craniotomy for cerebellar hemangioblastoma excision in a patient with von Hipel-Lindau disease complicated by uncontrolled hypertension due to pheochromocytoma

This report describes a patient with Von Hippel-Lindau (VHL) syndrome and uncontrolled hypertension due to pheochromocytoma who underwent craniotomy for the excision of a cerebellar hemangioblastoma combined with a laparoscopic adrenalectomy. A 31-year-old man presented with severe headache. MRI showed areas of abnormal enhancement in the left cerebellum that were determined to be hemangioblastoma with mass effect and obstructive hydrocephalus. His blood pressure rose abruptly and could not be controlled. CT of the abdomen revealed bilateral suprarenal tumors, and the patient was diagnosed as having VHL syndrome.On the third day, he presented with increasing headache, a decreased level of consciousness, and hemiparesis. We were not able to perform an craniotomy because abdominal compression in the prone or sitting position resulted in severe hypertension. We performed ventricular drainage to control his ICP. On the fifth day, we first performed a bilateral laparoscopic adrenalectomy to control ICP and then moved the patient to the prone position before performing a craniotomy to remove the left cerebellar hemangioblastoma. DISCU: ssion & conclusion In patients with pheochromocytoma, the effects of catecholamine oversecretion can cause significant perioperative morbidity and mortality, but these can be prevented by appropriate preoperative medical management. When carrying out an excision of cerebellar hemangioblastomas in patients with intracranial hypertension complicated by abnormal hypertension due to pheochromocytoma whose blood pressure is not sufficiently controlled, tumor resection of the pheochromocytoma prior to cerebellar hemangioblastoma excision in the same surgery may prevent increased ICP and reduce perioperative risk.

International Journal of Surgery Case Reports


N-Butyl-2-cyanoacrylate Embolization of an Intraosseous Dural Arteriovenous Fistula Associated With Acute Epidural Hematoma: Technical Case Report

Intraosseous dural arteriovenous fistulae (DAVF) are rare, especially those with drainage into the diploic venous system. The clinical presentation depends on the location of the lesion. This is the first report of an intraosseous DAVF associated with acute epidural hematoma. A 25-year-old man presented with headache and nausea. Imaging of the brain revealed abnormal signals indicative of acute epidural hematoma in the right frontal convexity. Angiography demonstrated a DAVF in the region of the frontal bone. Right external carotid artery angiography showed that the DAVF was fed mainly by the right middle meningeal artery with drainage into diploic veins. Immediately after embolization of the middle meningeal and the distal internal maxillary artery with 17% N-butyl-2-cyanoacrylate, the shunt was completely occluded. The patient was discharged 4 days later without clinical complications. Intraosseous DAVF can be treated by surgical resection or endovascular embolization. Curative treatment requires careful inspection of the angiographic architecture and microsurgical anatomy.


Safety and tolerability of desmoteplase within 3 to 9 hours after symptoms onset in Japanese patients with ischemic stroke

This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke. Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 μg/kg and then 90 μg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography. The incidence of symptomatic intracranial hemorrhage (≤72 hours) was defined as the primary end point. The occurrence of asymptomatic ICH, symptomatic cerebral edemas, and adverse events were other safety outcomes of special interest. Symptomatic intracranial hemorrhage was observed within 72 hours in 2 patients treated with placebo and in 1 patient treated with 70 μg/kg desmoteplase. Any ICH (symptomatic or asymptomatic ICH) within 72 hours were observed in 7 (43.8%) patients treated with placebo, in 8 (50%) patients treated with 70 μg/kg desmoteplase, and in 9 (56.3%) patients treated with 90 μg/kg desmoteplase. Desmoteplase treatment with 70 or 90 μg/kg was not associated with an increased risk of symptomatic cerebral edema compared with placebo. There were no other serious safety concerns associated with desmoteplase. Desmoteplase in both 70 and 90 μg/kg doses had a favorable safety profile and was well tolerated in Japanese patients with acute ischemic stroke when administered 3 to 9 hours after stroke symptoms onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01104467.


Therapeutically Targeting Tumor Necrosis Factor-/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage.

Vascular smooth muscle cell TNF and sphingosine-1-phosphate signaling significantly enhance cerebral artery tone in SAH; anti-TNF and anti-sphingosine-1-phosphate treatment may significantly improve clinical outcome.


Radiation-induced meningiomas after BNCT in patients with malignant glioma,

Of the 180 patients with malignant brain tumors whom we treated with boron neutron capture therapy (BNCT) since 1968, only one (0.56%) developed multiple radiation-induced meningiomas. The parasagittal meningioma that had received 42 Gy (w) for BNCT showed more rapid growth on Gd-enhanced MRI scans and more atypical features on histopathologic studies than the temporal convexity tumor that had received 20 Gy (w). Long-term follow up MRI studies are necessary in long-survivors of malignant brain tumors treated by BNCT.


Increasing upper-limb joint range of motion in post-stroke hemiplegic patients by daily hair-brushing.


Intraoperative Arachnoid Plasty Has Possibility to Prevent Chronic Subdural Hematoma after Surgery for Unruptured Cerebral Aneurysms.

Some patients develop chronic subdural hematomas (CSDHs) after the clipping/coating of unruptured aneurysms. The risk factors are not well understood and while no preventive methods are currently available, arachnoid plasty (ARP) may intercept the development of postoperative CSDH. We investigated the risk factors for CSDH and the usefulness of ARP to prevent postoperative CSDH. Between January 2009 and June 2013, 393 patients underwent 416 aneurysm surgeries via the pterional approach at Kushiro Kojinkai Memorial Hospital. Of these, 394 aneurysms (371 patients) were included in this study. Using multivariate analysis we evaluated the relationship between the patient demographics and clinical characteristics, and the development of postoperative symptomatic CSDH. We also studied the effect of ARP performed during aneurysm surgery. We found that symptomatic CSDH developed after 20 (5.1%) of the 394 operations; it was addressed by burr hole surgery and evacuation/irrigation. Male gender, advanced age, and oral anticoagulant therapy were significant risk factors for CSDH. Additive ARP, performed in the course of 132 surgeries (33.5%) was found to be a significant negative risk factor. The incidence of CSDH was significantly lower in patients who had undergone ARP than in patients who had not undergone it (0.8% vs. 7.3%, p < 0.01). We first report that ARP is useful for the prevention of CSDH in patients treated by aneurysm surgery.


Protective Role of Peroxisome Proliferator-Activated Receptor-γ in the Development of Intracranial Aneurysm Rupture.

Inflammation is emerging as a key component of the pathophysiology of intracranial aneurysms. Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear hormone receptor of which activation modulates various aspects of inflammation. Using a mouse model of intracranial aneurysm, we examined the potential roles of PPARγ in the development of rupture of intracranial aneurysm. A PPARγ agonist, pioglitazone, significantly reduced the incidence of ruptured aneurysms and the rupture rate without affecting the total incidence aneurysm (unruptured aneurysms and ruptured aneurysms). PPARγ antagonist (GW9662) abolished the protective effect of pioglitazone. The protective effect of pioglitazone was absent in mice lacking macrophage PPARγ. Pioglitazone treatment reduced the mRNA levels of inflammatory cytokines (monocyte chemoattractant factor-1, interleukin-1, and interleukin-6) that are primarily produced by macrophages in the cerebral arteries. Pioglitazone treatment reduced the infiltration of M1 macrophage into the cerebral arteries and the macrophage M1/M2 ratio. Depletion of macrophages significantly reduced the rupture rate. Our data showed that the activation of macrophage PPARγ protects against the development of aneurysmal rupture. PPARγ in inflammatory cells may be a potential therapeutic target for the prevention of aneurysmal rupture.


The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats

Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+)) rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which characterizes water-free Na(+) accumulation, was associated with detrimental vascular effects independent of the blood pressure (BP). We hypothesized that an increase in brain water-free Na(+) accumulation is associated with ischemic brain damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase in the brain Na(+)/water ratio was positively correlated with expansion of the cortical infarct volume without affecting the BP. Interestingly, OVX(+) was associated with the decreased expression of ATP1α3, a subtype of the Na(+) efflux pump. HSD increased the expression of brain Na(+) influx-related molecules and the mineralocorticoid receptor (MR). The pretreatment of OVX(+)/HSD rats with the MR antagonist eplerenone reduced brain water-free Na(+) accumulation, up-regulated ATP1α3, down-regulated MR, and reduced the cortical infarct volume. Our findings show that the increase in the brain Na(+)/water ratio elicited by estrogen deficiency or HSD is associated with ischemic brain damage BP-independently, suggesting the importance of regulating the accumulation of brain water-free Na(+). The up-regulation of ATP1α3 and the down-regulation of MR may provide a promising therapeutic strategy to attenuate ischemic brain damage in postmenopausal women.


PPAR-dependent- and -independent inhibition of the HMGB1/TLR9 Pathway by EPA attenuates ischemic brain damage in ovariectomized rats

High mobility group box 1 (HMGB1) elevation after cerebral ischemia activates inflammatory pathways via receptors such as the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) and leads to brain damage. Eicosapentaenoic acid (EPA), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, attenuates postischemic inflammation and brain damage in male animals. However, postischemic HMGB1 signaling and the effects of EPA on ovariectomized (OVX(+)) rats remain unclear. We hypothesized that EPA attenuates brain damage in OVX(+) rats via the inhibition of HMGB1 signaling in a PPARγ-dependent manner. Seven-week-old female Sprague-Dawley rats were divided into 3 groups; nonovariectomized (OVX(-)) rats and EPA-treated and EPA-untreated OVX(+) rats before cerebral ischemia induction. Another set of EPA-treated OVX(+) rats was injected with the PPARγ inhibitor GW9662. OVX(+) decreased the messenger RNA level of PPARγ and increased that of HMGB1, RAGE, TLR9, and tumor necrosis factor alpha (TNFα) in parallel with ischemic brain damage. EPA restored the PPARγ expression, downregulated the HMGB1 signal-related molecules, and attenuated the ischemic brain damage. Neither OVX(+) nor EPA affected the expression of TLR2 or TLR4. Interestingly, GW9662 partially abrogated the EPA-induced neuroprotection and the downregulation of RAGE and TLR9. In contrast, GW9662 did not affect HMGB1 or TNFα. These results suggest that EPA exerts PPARγ-dependent and PPARγ-independent effects on postischemic HMGB1/TLR9 pathway. The cortical infarct volume exacerbated by OVX(+) is associated with the upregulation of the HMGB1/TLR9 pathway. Suppression of this pathway may help to limit ischemic brain damage in postmenopausal women.

Journal of Stroke & Cerebrovascular Diseases


Improvement of plasma biomarkers after switching stroke patients from other angiotensin II type I receptor blockers to olmesartan

Managing hypertension is crucial for preventing stroke recurrence. Some stroke patients experience resistant hypertension. In our experimental stroke model, olmesartan increased the expression of angiotensin (Ang) II converting enzyme-2. We hypothesized that switching to olmesartan affects biomarkers and the blood pressure (BP) in stroke patients whose BP is insufficiently controlled by standard doses of Ang II type I receptor blockers (ARBs) other than olmesartan. We recruited 25 patients to study our hypothesis. All had a history of stroke or silent cerebral infarction. We switched them to olmesartan (10-40 mg per day) for 12 weeks and determined their plasma level of Ang-(1-7), peroxiredoxin, oxidized low-density lipoprotein (oxLDL)/β-2-glycoprotein I (β2GPI) complex, adiponectin, high mobility group box 1 (HMGB1), and tumor necrosis factor-α (TNFα) and recorded their BP before and after olmesartan treatment. After switching the patients to olmesartan, their plasma level of Ang-(1-7) as a vasoprotective indicator and adiponectin regulating metabolic syndrome was increased, and peroxiredoxin and the oxLDL/β2GPI complex indicating its antioxidative stress and its proatherogenicity were lower than their baseline. This suggests that olmesartan may be more effective than other ARBs to improve these conditions. Neither HMGB1 nor TNFα reflecting an inflammatory response was affected, suggesting that the anti-inflammatory effects of olmesartan are similar to those of other ARBs. The recommended BP (<140/90) was obtained in 10 of the 25 patients after switching to olmesartan. No adverse events occurred. Switching from other ARBs to olmesartan may be a promising therapeutic option in patients with resistant hypertension.


Predictability of the future development of aggressive behavior of cranial dural arteriovenous fistulas based on decision tree analysis.

OBJECT The severity of clinical signs and symptoms of cranial dural arteriovenous fistulas (DAVFs) are well correlated with their pattern of venous drainage. Although the presence of cortical venous drainage can be considered a potential predictor of aggressive DAVF behaviors, such as intracranial hemorrhage or progressive neurological deficits due to venous congestion, accurate statistical analyses are currently not available. Using a decision tree data mining method, the authors aimed at clarifying the predictability of the future development of aggressive behaviors of DAVF and at identifying the main causative factors. METHODS Of 266 DAVF patients, 89 were eligible for analysis. Under observational management, 51 patients presented with intracranial hemorrhage/infarction during the follow-up period. RESULTS The authors created a decision tree able to assess the risk for the development of aggressive DAVF behavior. Evaluated by 10-fold cross-validation, the decision tree's accuracy, sensitivity, and specificity were 85.28%, 88.33%, and 80.83%, respectively. The tree shows that the main factor in symptomatic patients was the presence of cortical venous drainage. In its absence, the lesion location determined the risk of a DAVF developing aggressive behavior. CONCLUSIONS Decision tree analysis accurately predicts the future development of aggressive DAVF behavior.


Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice

Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling, which are processes that have important roles in the pathophysiology of intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in the development of intracranial aneurysm rupture using a mouse model of intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10 mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks. Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. The protective effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7) was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and aneurysms, Mas receptor mRNA expression was very scarce in these tissues. Angiotensin-(1-7) reduced the expression of tumor necrosis factor-α and interleukin-1β in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner.

Journal of Cerebral Blood Flow and Metabolism


Development of a highly sensitive immunohistochemical method to detect neurochemical molecules in formalin-fixed and paraffin-embedded tissues from autopsied human brains.

Immunohistochemistry (IHC) is a valuable method for identifying discrete neurochemical molecules by the interaction of target antigens with validated antibodies tagged with a visible label (e.g., peroxidase). We have developed an immunostaining method that is highly sensitive in detection of neurochemical antigens. Our IHC method, which we call the PBTA method, involves a hybrid protocol that implements aspects of both the polymer and avidin-biotin-complex (ABC) methods in combination with biotin-tyramide amplification. When using [Met]-enkephalin as a target antigen, the sensitivity of the PBTA method for IHC was more than 100-fold higher compared with the polymer and ABC methods. In addition, its sensitivity for enzyme-linked immunosorbent assay was about 1,000-fold higher compared with the ABC method. We examined the utility of our IHC method for both chromogenic and fluorescence detection systems used to visualize neurochemical peptides and proteins in formalin-fixed, paraffin-embedded tissues from autopsied human brains. The results convincingly demonstrate that under optimal conditions, our IHC method is highly sensitive without increasing non-specific background activities. Our IHC method could be a powerful tool for detection and visualization of neurochemical antigens that are present even in trace amounts in autopsied human brains.


スマートデバイスとインターネットを用いた医療過疎地域での脳卒中支援システムの導入


Diagnosis of brain tumors using dynamic contrast-enhanced perfusion imaging with a short acquisition time

This study sought to determine the diagnostic utility of perfusion parameters derived from dynamic contrast-enhanced (DCE) perfusion MRI with a short acquisition time (approximately 3.5 min) in patients with glioma, brain metastasis, and primary CNS lymphoma (PCNSL). Twenty-six patients with 29 lesions (4 low-grade glioma, 13 high-grade glioma, 7 metastasis, and 5 PCNSL) underwent DCE-MRI in a 3 T scanner. A ROI was placed on the hotspot of each tumor in maps for volume transfer contrast K (trans) , extravascular extracellular volume V e , and fractional plasma volume V p . We analyzed differences in parameters between tumors using the Mann-Whitney U test. We calculated sensitivity and specificity using receiver operating characteristics analysis. Mean K (trans) values of LGG, HGG, metastasis and PCNSL were 0.034, 0.31, 0.38, 0.44, respectively. Mean Ve values of each tumors was 0.036, 0.57, 0.47, 0.96, and mean Vp value of each tumors was 0.070, 0.086, 0.26, 0.17, respectively. Compared with other tumor types, low-grade glioma showed lower K (trans) (P < 0.01, sensitivity = 88%, specificity = 100%) and lower V e (P < 0.01, sensitivity = 96%, specificity = 100%). PCNSL showed higher V e (P < 0.01, sensitivity = 100%, specificity = 88%), but the other perfusion parameters overlapped with those of different histology. Kinetic parameters derived from DCE-MRI with short acquisition time provide useful information for the differential diagnosis of brain tumors.