Kohhei Nakajima and Shinji Nagahiro : 脳神経外科周術期管理のすべて 意識障害・脳ヘルニア，脳死, Medicus SHUPPAN, Tokyo, Mar. 2014.
5.
Ryoma Morigaki, Ryuji Kaji, Shinji Nagahiro and Satoshi Goto : Thalamic deep brain stimulation for Parkinsons disease., 2011.
6.
Ryoma Morigaki, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Current use of thalamic surgeries or treating movement disorders, 2011.
7.
有田 憲生 and Shinji Nagahiro : 脳腫瘍手術のすべて 手技の工夫と要点が動画ですばやく理解できる, Medicus SHUPPAN, 2010.
8.
Hwan Ki Park, Yoshiteru Urai, Osamu Jinnouchi, Atsuhiko Suzue, Tokujiro Kanamori, Kyung Tak Kwak, Oded-Ben Yoseph, Shinji Nagahiro and Kiyoshi Fukui : 6-12 Astroglial expression of D-amino acid oxidase, --- regional and cell-type specific expression ---, Nova Science Publishers, New York, Jan. 2007.
Academic Paper (Judged Full Paper):
1.
Shinji Nagahiro, Yoshifumi Mizobuchi, Kohhei Nakajima and Yasushi Takagi : A Novel Approach to Microvascular Decompression for Hemifacial Spasm: Method Description and Associated Outcome, Operative Neurosurgery, Vol.00, 1-7, 2022.
(Summary)
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.
Kei Tanaka, Shinji Nagahiro and Hiroshi Bandou : "Further Hospital Art Development of Masking Tape Using Thin Film Sheet", Asploro Journal of Biomedical and Clinical Case Reports, Vol.4, No.3, 195-198, 2021.
Kei Tanaka, Shinji Nagahiro and Hiroshi Bandou : "Cœur résonant": online hospital art creation with people in the distance, Global Journal of Arts and Social Sciences, Vol.3, No.4, 1-2, 2021.
(Keyword)
Tokushirna University Hospital Art Labo (THAL) / Masking tape / film sheets / BNP Parisbas / Social actiqn program
Kei Tanaka, Shinji Nagahiro and Hiroshi Bandou : Psychologically comfortable seasonal images for the project on the art in hospitals, Arts & Humanities Open Access Journal, Vol.4, No.5, 187-189, 2020.
Kei Tanaka, Shinji Nagahiro and Hiroshi Bandou : Beneficial Art in Hospitals with Masking Tape Initiated from University Hospital, Asploro Journal of Biomedical and Clinical Case Reports, Vol.3, No.3, 202-206, 2020.
Akemi Hioka, Yoshiteru Tada, Keiko Kitazato, Naoki Akazawa, Yasushi Takagi and Shinji Nagahiro : Action observation treatment improves gait ability in subacute to convalescent stroke patients., Journal of Clinical Neuroscience, Vol.75, 55-61, 2020.
(Summary)
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.
Eiji Shikata, Tetsuya Tamura, Kiyohito Shinno, Yoshihiro Okayama, Naoki Shinohara, Kenji Shimada, Yasuhisa Kanematsu, Keiko T Kitazato, Shinji Nagahiro and Yasushi Takagi : Importance of Managing the Water-Electrolyte Balance by Delivering the Optimal Minimum Amount of Water and Sodium After Subarachnoid Hemorrhage., World Neurosurgery, Vol.129, e352-e360, 2019.
(Summary)
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.
Toshiyuki Okazaki, Yasuhisa Kanematsu, Kenji Shimada, Masaaki Korai, Junichiro Satomi, Masaaki Uno, Shinji Nagahiro and Yasushi Takagi : A Single-center Retrospective Study with 5- and 10-year Follow-up of Carotid Endarterectomy with Patch Graft., Neurologia Medico-Chirurgica, Vol.59, No.6, 231-237, 2019.
(Summary)
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.
Akemi Hioka, Yoshiteru Tada, Keiko Kitazato, Yasuhisa Kanematsu, Yoshifumi Mizobuchi, Hideo Mure, Kenji Shimada, Toshiyuki Okazaki, Masaaki Korai, Noki Akazawa, Yuki Matsumoto, Yuki Matsumoto, Yasushi Takagi and Shinji Nagahiro : Activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons., Journal of Clinical Neuroscience, Vol.60, 79-83, 2019.
(Summary)
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.
Yoshifumi Mizobuchi, Kohhei Nakajima, Toshitaka Fujihara, Kazuhito Matsuzaki, Hideo Mure, Shinji Nagahiro and Yasushi Takagi : The risk of hemorrhage in stereotactic biopsy for brain tumors., The Journal of Medical Investigation : JMI, Vol.66, No.3,4, 314-318, 2019.
(Summary)
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.
(Keyword)
Adolescent / Adult / Aged / Aged, 80 and over / Biopsy / Brain / Brain Neoplasms / Cerebral Hemorrhage / Female / Humans / Male / Middle Aged / Stereotaxic Techniques / Young Adult
Shinji Nagahiro, Yoshiteru Tada, Junichiro Satomi, Tomoya Kinouchi, Kazuyuki Kuwayama, Kenji Yagi, Kohhei Nakajima, Nobuhisa Matsushita, Takeshi Miyamoto, Tadashi Yamaguchi, Kenji Shimada, Masaaki Korai, Hideo Mure, Y Okayama, Takashi Abe, Masafumi Harada, Keiko T. Kitazato and Yasuhisa Kanematsu : Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study., Journal of Stroke & Cerebrovascular Diseases, Vol.27, No.8, 2134-2140, 2018.
(Summary)
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.
N Enomoto, Hideo Mure, Toshiyuki Okazaki, M Azumi, S Okita, Shinji Nagahiro and Yasushi Takagi : Posttraumatic Cerebrospinal Fluid Leak Associated with an Upper Cervical Meningeal Diverticulum, World Neurosurgery, Vol.116, 50-55, 2018.
(Summary)
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.
Yasuhisa Kanematsu, Junichiro Satomi, Masaaki Korai, Toshiyuki Okazaki, Idumi Yamaguchi, Yoshiteru Tada, Masaaki Uno, Shinji Nagahiro and Yasushi Takagi : Flow Alteration Therapy for Ruptured Vertebral Artery Dissecting Aneurysms Involving the Posterior Inferior Cerebellar Artery, Neurologia Medico-Chirurgica, Vol.58, 341-349, 2018.
(Summary)
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.
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohhei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, KT Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro and Yasushi Takagi : 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, Journal of Neuro-Oncology, Vol.139, No.2, 323-332, 2018.
(Summary)
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.
Toshiyuki Okazaki, Shinsuke Irie, Toru Inagaki, Osamu Saito, Motoshige Yamashina, Hitoshi Hayase, Hiroshi Nakagawa, Shinji Nagahiro and Koji Saito : Coloring Techinique of Magnetic Resonance Angiography for Superficial Temporal Artery to Middle Cerebral Artery Bypass surgery, World Neurosurgery, Vol.112, No.112, e113-e118, 2018.
(Summary)
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.
Toshiyuki Okazaki, Hitoshi Nakagawa, Hitoshi Hayase, Shinsuke Irie, Toru Inagaki, Osamu Saito, Motoshige Yamashita, Shinji Nagahiro and Koji Saito : Idiopathic and Chronic Epidural Hematoma in the Lumbar Spine: A Case Report and Review of Literatures, Neurologia Medico-Chirurgica, Vol.58, No.3, 138-144, 2018.
(Summary)
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.
GA Davis, RG Ellenbogen, J Bailes, RC Cantu, KM Johnston, GT Manley, Shinji Nagahiro, A Sills, CH Tator and P McCrory : The Berlin international consensus meeting on concussion in sport., Neurosurgery, Vol.82, No.2, 232-236, 2018.
(Summary)
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.
Tomoya Kinouchi, Keiko T. Kitazato, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Nobuhisa Matsushita, Yoshitaka Kurashiki, Junichiro Satomi, Masataka Sata and Shinji Nagahiro : 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., Translational Stroke Research, Vol.9, No.3, 306-316, 2017.
(Summary)
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.
Hidetsugu Maekawa, Yoshiteru Tada, Kenji Yagi, Takeshi Miyamoto, Kitazato T. Keiko, Masaaki Korai, Junichiro Satomi, Tomoki Hashimoto and Shinji Nagahiro : Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats., Journal of Neuroinflammation, Vol.2, No.14, 197, 2017.
(Summary)
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.
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.
Kiyoe Kurahashi, Itsuro Endo, Takeshi Kondo, Kana Morimoto, Sumiko Yoshida, Akio Kuroda, Ken-ichi Aihara, Munehide Matsuhisa, Kohhei Nakajima, Yoshifumi Mizobuchi, Shinji Nagahiro, Masahiro Abe and Seiji Fukumoto : Remarkable Shrinkage of a Growth Hormone (GH)-secreting Macroadenoma Induced by Somatostatin Analogue Administration: A Case Report and Literature Review., Internal Medicine, Vol.56, No.18, 2455-2461, 2017.
(Summary)
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.
Nobuaki Yamamoto, Junichiro Satomi, Yuki Yamamoto, Kenji Shono, Yasuhisa Kanematsu, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : Risk Factors of Neurological Deterioration in Patients with Cerebral Infarction due to Large Artery Atherosclerosis, Journal of Stroke & Cerebrovascular Diseases, Vol.26, No.8, 1801-1806, 2017.
(Summary)
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.
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.
Teruyoshi Kageji, Yoshifumi Mizobuchi, Kohhei Nakajima and Shinji Nagahiro : Postoperative Hematoma Requiring Recraniotomy in 1149 Consecutive Patients with Intracranial Tumors, Operative Neurosurgery, Vol.13, No.3, 392-397, 2017.
(Summary)
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.
Paul McCrory, Willem Meeuwisse, Jiří Dvořák, Mark Aubry, Julian Bailes, Steven Broglio, Robert C. Cantu, David Cassidy, Ruben J. Echemendia, Rudy J. Castellani, Gavin A. Davis, Richard Ellenbogen, Carolyn Emery, Lars Engebretsen, Nina Feddermann-Demont, Christopher C. Giza, Kevin M. Guskiewicz, Stanley Herring, Grant L. Iverson, Karen M. Johnston, James Kissick, Jeffrey Kutcher, John J. Leddy, David Maddocks, Michael Makdissi, Geoff T. Manley, Michael McCrea, William P. Meehan, Shinji Nagahiro, Jon Patricios, Margot Putukian, Kathryn J. Schneider, Allen Sills, Charles H. Tator, Michael Turner and Pieter E. Vos : Consensus statement on concussion in sport - the 5th international conference on concussion in sport held in Berlin, October 2016, British Journal of Sports Medicine, Vol.51, No.11, 838-847, 2017.
Yasuhisa Kanematsu, Junichiro Satomi, Kazuyuki Kuwayama, Izumi Yamaguchi, Shotaroh Yoshioka, Tomoya Kinouchi, Yoshiteru Tada, Nobuaki Yamamoto, Shunji Matsubara, Kenji Shono and Shinji Nagahiro : 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, Neurologia Medico-Chirurgica, Vol.57, No.6, 278-283, 2017.
(Summary)
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.
Kazuyuki Kuwayama, Junichiro Satomi, Tadashi Yamaguchi, Idumi Yamaguchi, Shu Sogabe, Shotaroh Yoshioka and Shinji Nagahiro : Pulsatile Tinnitus due to an Aberrant Internal Carotid Artery in the Middle Ear:A Case Report, Neurological Surgery, Vol.45, No.4, 321-324, 2017.
Shu Sogabe, Junichiro Satomi, Yoshiteru Tada, Yasuhisa Kanematsu, Kazuyuki Kuwayama, Kenji Yagi, Shotaroh Yoshioka, Yoshifumi Mizobuchi, Hideo Mure, Izumi Yamaguchi, Takashi Abe, Nobuaki Yamamoto, Keiko Kitazato, Ryuji Kaji, Masafumi Harada and Shinji Nagahiro : Intra-arterial high signals on arterial spin labeling perfusion images predict the occluded internal carotid artery segment, Neuroradiology, Vol.59, No.6, 587-595, 2017.
(Summary)
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.
Kenji Yagi, Hiroshi Nakagawa, Toshiyuki Okazaki, Shinsuke Irie, Toru Inagaki, Osamu Saito, Shinji Nagahiro and Koji Saito : Noninfectious prevertebral soft-tissue inflammation and hematoma eliciting swelling after anterior cervical discectomy and fusion., Journal of Neurosurgery. Spine, Vol.26, No.4, 459-465, 2017.
(Summary)
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.
Aya Sato, Yoshifumi Mizobuchi, Kohhei Nakajima, Kenji Shono, Toshitaka Fujihara, Teruyoshi Kageji, Keiko Kitazato, Kazuhito Matsuzaki, Hideo Mure, Kazuyuki Kuwayama, Akiko Sumi, Hideyuki Saya, Oltea Sampetrean and Shinji Nagahiro : Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma., Journal of Neuro-Oncology, Vol.132, No.2, 231-238, 2017.
(Summary)
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.
Carolyn A. Emery, Amanda M. Black, Ash Kolstad, German Martinez, Alberto Nettel-Aguirre, Lars Engebretsen, Karen Johnston, James Kissick, David Maddocks, Charles Tator, Mark Aubry, Jiří Dvořák, Shinji Nagahiro and Kathryn Schneider : What strategies can be used to effectively reduce the risk of concussion in sport?, British Journal of Sports Medicine, Vol.51, No.12, 978-984, 2017.
(Summary)
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.
(Keyword)
Athletes / Athletic Injuries / Basketball / Brain Concussion / Football / Head Protective Devices / Hockey / Humans / Mouth Protectors / Risk Reduction Behavior / Skiing / Soccer
Yoshifumi Mizobuchi, Kenji Muramatsu, Makoto Ohtani, Junichiro Satomi, Kiyohide Fushimi, Shinya Matsuda and Shinji Nagahiro : 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, Neurologia Medico-Chirurgica, Vol.57, No.4, 184-190, 2017.
(Summary)
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.
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.
Nobuaki Yamamoto, Junichiro Satomi, Yuki Yamamoto, Izumi Yamaguchi, Shinji Nagahiro and Ryuji Kaji : Usefulness of 3-Tesla magnetic resonance arterial spin-labeled imaging for diagnosis of cranial dural arteriovenous fistula, Journal of the Neurological Sciences, Vol.372, 428-432, 2017.
(Summary)
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.
Toshiyuki Okazaki, Hiroshi Nakagawa, Kenji Yagi, Hitoshi Hayase, Shinji Nagahiro and Koji Saito : Bone scintigraphy for the diagnosis of the responsible level of osteoporotic vertebral compression fractures in percutaneous balloon kyphoplasty, Clinical Neurology and Neurosurgery, Vol.152, 23-27, 2017.
(Summary)
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.
(Keyword)
Aged / Aged, 80 and over / Female / Fractures, Compression / Humans / Kyphoplasty / Male / Middle Aged / Osteoporotic Fractures / Radionuclide Imaging / Spinal Fractures
Kenji Shono, Junichiro Satomi, Yoshiteru Tada, Yasuhisa Kanematsu, Nobuaki Yamamoto, Yuishin Izumi, Ryuji Kaji, Masafumi Harada and Shinji Nagahiro : Optimal Timing of Diffusion-Weighted Imaging to Avoid False-Negative Findings in Patients With Transient Ischemic Attack, Stroke, Vol.48, No.7, 1990-1992, 2017.
(Summary)
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.
(Keyword)
Aged / Aged, 80 and over / Diffusion Magnetic Resonance Imaging / False Negative Reactions / Female / Humans / Ischemic Attack, Transient / Male / Middle Aged / Retrospective Studies / Risk Factors / Sensitivity and Specificity / Time Factors
Izumi Yamaguchi, Junichiro Satomi, Nobuaki Yamamoto, Shotaroh Yoshioka, Yoshiteru Tada, Kenji Yagi, Yasuhisa Kanematsu and Shinji Nagahiro : Coexistence of Quasi-moyamoya Disease and POEMS Syndrome in a Patient with Intracranial Hemorrhage: A Case Report and Literature Review, NMC Case Report Journal, Vol.4, 5-9, 2017.
(Summary)
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.
Akemi Hioka, Yoshifumi Mizobuchi, Yoshiteru Tada, Kyoko Nishi, Yasuhiko Shirayama, Shinsuke Katoh, N Akazawa, Ryuji Kaji, Y Ojima and Shinji Nagahiro : Usefulness of a novel higher brain dysfunction screening test for evaluating higher brain function in healthy persons., The Journal of Medical Investigation : JMI, Vol.64, No.3.4, 280-285, 2017.
(Summary)
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.
Mungunbagana Ganbold, Masafumi Harada, Delgerdalai Khashbat, Takashi Abe, Teruyoshi Kageji and Shinji Nagahiro : 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, The Journal of Medical Investigation : JMI, Vol.64, No.1.2, 58-63, 2017.
(Summary)
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.
Ryoma Morigaki, Hideo Mure, Ryuji Kaji, Shinji Nagahiro and Satoshi Goto : Therapeutic Perspective on Tardive Syndrome with Special Reference to Deep Brain Stimulation, Frontiers in Psychiatry, Vol.7, 207, 2016.
(Summary)
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.
蔭山 彩人, Yasuhisa Kanematsu, 山口 泉, Nobuaki Yamamoto, Tomoya Kinouchi, Yoshiteru Tada, Kyoko Nishi, Junichiro Satomi and Shinji Nagahiro : In-hospital ischemic stroke at Tokushima University Hospital, Shikoku Acta Medica, Vol.72, No.5-6, 195-198, 2016.
(Summary)
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.
Teruyoshi Kageji, Takeshi Miyamoto, Yumiko Kotani, Tuyoshi Kaji, Yoshimi Bando, Yoshifumi Mizobuchi, Kohhei Nakajima and Shinji Nagahiro : Congenital craniopharyngioma treated by radical surgery: case report and review of the literature, Child's Nervous System, Vol.33, No.2, 357-362, 2016.
(Summary)
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.
Toshiyuki Uehara, Kazuo Minematsu, Tomoyuki Ohara, Kazumi Kimura, Yasushi Okada, Yasuhiro Hasegawa, Norio Tanahashi, Akifumi Suzuki, Shigeharu Takagi, Jyoji Nakagawara, Kazumasa Arii, Shinji Nagahiro, Kuniaki Ogasawara, Shinichiro Uchiyama, Masayasu Matsumoto, Koji Iihara, Kazunori Toyoda and PROMISE-TIA investigators : Incidence, predictors, and etiology of subsequent ischemic stroke within one year after transient ischemic attack, International Journal of Stroke, Vol.12, No.1, 84-89, 2016.
(Summary)
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.
Delgerdalai Khashbat, Takashi Abe, Mungunbagana Ganbold, Seiji Iwamoto, Naoto Uyama, Saho Irahara, Youichi Otomi, Masafumi Harada, Teruyoshi Kageji and Shinji Nagahiro : Correlation of 3D Arterial Spin Labeling and Multi-Parametric Dynamic Susceptibility Contrast Perfusion MRI in Brain Tumors., The Journal of Medical Investigation : JMI, Vol.63, No.3-4, 175-181, 2016.
(Summary)
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.
布村 俊幸, Yasuhisa Kanematsu, 山上 圭, Kyoko Nishi, 山本 雄貴, Nobuaki Yamamoto, 安積 麻衣, 西山 徹, 鹿草 宏, 山口 泉, 吉岡 正太郎, Junichiro Satomi and Shinji Nagahiro : "Drip and Ship" Cases of Intravenous rt-PA Therapy Transported to stroke Care Unit, Shikoku Acta Medica, Vol.72, No.3-4, 107-112, 2016.
(Summary)
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.
Yoko Yamamoto, Toshiyuki Okazaki, Keishi Yoda, Yoshiteru Tada and Shinji Nagahiro : Successful emergency carotid endarterectomy after thrombolysis with intravenous recombinant tissue-type plasminogen activator, The Journal of Medical Investigation : JMI, Vol.63, No.3-4, 300-304, 2016.
(Summary)
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.
Junichiro Satomi, Hadeishi Hiromu, Yoshida Yasuji, Suzuki Akifumi and Shinji Nagahiro : Histopathological Findings in Brains of Patients Who Died in the Acute Stage of Poor-grade Subarachnoid Hemorrhage., Neurologia Medico-Chirurgica, 2016.
(Summary)
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.
Masaaki Korai, 北里 慶子, Yoshiteru Tada, Takeshi Miyamoto, Kenji Shimada, Nobuhisa Matsushita, Yasuhisa Kanematsu, Junichiro Satomi, 橋本 友紀 and Shinji Nagahiro : Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats, Journal of Neuroinflammation, Vol.13, No.1, 165, 2016.
(Summary)
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.
Mungunkhuyag Majigsuren, Takashi Abe, Teruyoshi Kageji, Kazuhito Matsuzaki, Mayumi Takeuchi, Seiji Iwamoto, Youichi Otomi, Naoto Uyama, Shinji Nagahiro and Masafumi Harada : Comparison of brain tumor contrast-enhancement on T1-CUBE and 3D-SPGR images, Magnetic Resonance in Medical Sciences, Vol.15, No.1, 34-40, 2016.
(Summary)
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.
(Keyword)
Adult / Aged / Aged, 80 and over / Astrocytoma / Brain Neoplasms / Contrast Media / Female / Gadolinium DTPA / Humans / Image Enhancement / Image Processing, Computer-Assisted / Imaging, Three-Dimensional / Lymphoma, Large B-Cell, Diffuse / magnetic resonance imaging / Male / Meningioma / Middle Aged / Oligodendroglioma / Signal-To-Noise Ratio / White Matter
Teruyoshi Kageji, Fumiaki Obata, Hirofumi Oka, Yasuhisa Kanematsu, Ryo Tabata, Kenji Tani, Hiroyashu Bando and Shinji Nagahiro : Drip-and-ship thrombolytic therapy Supported by the telestroke system for acute ischemic stroke patients living in medically under-served Areas., Neurologia Medico-Chirurgica, Vol.56, No.12, 753-758, 2016.
(Summary)
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.
(Keyword)
Aged / Aged, 80 and over / Female / Fibrinolytic Agents / Humans / Japan / Male / Medically Underserved Area / Stroke / Telemedicine / Thrombolytic Therapy / Time-to-Treatment / Tissue Plasminogen Activator / Treatment Outcome
Yoshifumi Mizobuchi and Shinji Nagahiro : A Review of Sport-Related Head Injuries, Korean Journal of Neurotrauma, Vol.12, No.1, 1-5, 2016.
(Summary)
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.
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.
Takeshi Miyamoto, DK Kung, KT Kitazato, Kenji Yagi, Kenji Shimada, Yoshiteru Tada, Masaaki Korai, Yoshitaka Kurashiki, Tomoya Kinouchi, Yasuhisa Kanematsu, Junichiro Satomi, T Hashimoto and Shinji Nagahiro : 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, Journal of Cerebral Blood Flow and Metabolism, Vol.37, No.8, 2795-2805, 2016.
(Summary)
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.
Ryoma Morigaki, Ryosuke Miyamoto, Shinya Ohkita, Yoshifumi Mizobuchi, Hideo Mure, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Nuclear factor kappa b is under the control of dopamine signaling in the mouse striatum, Neurologia Medico-Chirurgica, Vol.55, 305, 2016.
74.
Nobuaki Yamamoto, Junichiro Satomi, Yamamoto Yuki, Takahiro Furukawa, Yoshiteru Tada, Masafumi Harada, Shinji Nagahiro and Ryuji Kaji : 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, Journal of the Neurological Sciences, Vol.359, No.1-2, 141-145, 2015.
(Summary)
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.
Nobuaki Yamamoto, Junichiro Satomi, Yuishin Izumi, Yamamoto Yuki, Shinji Nagahiro and Ryuji Kaji : Predictors of a favorable outcome after recanalization in patients with cerebral major vessel occlusion, Journal of Stroke & Cerebrovascular Diseases, Vol.24, No.12, 2793-2799, 2015.
(Summary)
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.
Yoshifumi Mizobuchi, Teruyoshi Kageji, T Yamaguchi and Shinji Nagahiro : Craniotomy for cerebellar hemangioblastoma excision in a patient with von Hipel-Lindau disease complicated by uncontrolled hypertension due to pheochromocytoma, International Journal of Surgery Case Reports, Vol.17, 96-99, 2015.
(Summary)
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.
Shotaroh Yoshioka, Kazuyuki Kuwayama, Junichiro Satomi and Shinji Nagahiro : N-Butyl-2-cyanoacrylate Embolization of an Intraosseous Dural Arteriovenous Fistula Associated With Acute Epidural Hematoma: Technical Case Report, Neurosurgery, Vol.11, No.Suppl 3, E468-E471, 2015.
(Summary)
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.
(Keyword)
Adult / Central Nervous System Vascular Malformations / Cerebral Angiography / Drainage / Embolization, Therapeutic / Enbucrilate / Frontal Bone / Hematoma, Epidural, Cranial / Humans / Male / Maxillary Artery / Meningeal Arteries / Treatment Outcome
E Mori, K Minematsu, J Nakagawara, Y Hasegawa, Shinji Nagahiro, Y Okada, T Truelsen, A Lindsten, A Ogawa, T Yamaguchi and DIAS-J Investigators : Safety and tolerability of desmoteplase within 3 to 9 hours after symptoms onset in Japanese patients with ischemic stroke, Stroke, Vol.46, No.9, 2549-2554, 2015.
(Summary)
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.
Kenji Yagi, Darcy Lidington, Hoyee Wan, C Jessica Fares, Anja Meissner, Manabu Sumiyoshi, Jinglu Ai, D Warren Foltz, A Sergei Nedospasov, Stefan Offermanns, Shinji Nagahiro, Loch R Macdonald and Steffen-Sebastian Bolz : Therapeutically Targeting Tumor Necrosis Factor-/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage., Stroke, Vol.46, No.8, 2260-2270, 2015.
(Summary)
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.
Teruyoshi Kageji, Kenji Shono, Yoshifumi Mizobuchi, Kohhei Nakajima, Shinji Nagahiro and Y Nakagawa : Radiation-induced meningiomas after BNCT in patients with malignant glioma,, Applied Radiation and Isotopes, Vol.106, 256-259, 2015.
(Summary)
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.
Takako Minagawa, Ayako Tamura, Takako Ichihara, Yukari Hisaka and Shinji Nagahiro : Increasing upper-limb joint range of motion in post-stroke hemiplegic patients by daily hair-brushing., British Journal of Neuroscience Nursing, Vol.11, No.3, 112-117, 2015.
Kenji Yagi, Shinsuke Irie, Toru Inagaki, Yosuke Ishii, Osamu Saito, Tejin Lee, Hiroshi Nakagawa, Koji Saito and Shinji Nagahiro : Intraoperative Arachnoid Plasty Has Possibility to Prevent Chronic Subdural Hematoma after Surgery for Unruptured Cerebral Aneurysms., Neurologia Medico-Chirurgica, Vol.55, No.6, 493-497, 2015.
(Summary)
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.
Kenji Shimada, Hjime Furukawa, Kousuke Wada, Masaaki Kohrai, Yuan Wei, Yoshiteru Tada, Atsushi Kuwahara, Fumiaki Shikata, Keiko T. Kitazato, Shinji Nagahiro, Michael T. Lawton and Tomoki Hashimoto : Protective role of peroxisome proliferator-activated receptor- in the development of intracranial aneurysm rupture, Stroke, Vol.46, No.6, 1664-1672, 2015.
(Summary)
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.
Manabu Sumiyoshi, T Keiko Kitazato, Kenji Yagi, Takeshi Miyamoto, Yoshitaka Kurashiki, Nobuhisa Matsushita, Tomoya Kinouchi, Kazuyuki Kuwayama, Junichiro Satomi and Shinji Nagahiro : The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats, Brain Research, Vol.1616, 37-44, 2015.
(Summary)
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.
Manabu Sumiyoshi, Junichiro Satomi, KT Kitazato, Kenji Yagi, Yoshitaka Kurashiki, Masaaki Korai, Takeshi Miyamoto, Kazuyuki Kuwayama and Shinji Nagahiro : PPAR-dependent- and -independent inhibition of the HMGB1/TLR9 Pathway by EPA attenuates ischemic brain damage in ovariectomized rats, Journal of Stroke & Cerebrovascular Diseases, Vol.24, No.6, 1187-1195, 2015.
(Summary)
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.
Yoshiteru Tada, Kenji Yagi, Masaaki Uno, Nobuhisa Matsushita, Yasuhisa Kanematsu, Kazuyuki Kuwayama, Kenji Shimada, Kyoko Nishi, Motohiro Hirasawa, Junichiro Satomi, KT Kitazato, Teruyoshi Kageji, E Matsumura and Shinji Nagahiro : Improvement of plasma biomarkers after switching stroke patients from other angiotensin II type I receptor blockers to olmesartan, Journal of Stroke & Cerebrovascular Diseases, Vol.24, 1487-1492, 2015.
(Summary)
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.
Junichiro Satomi, AHMAD AMMAR GHAIBEH, Hiroki Moriguchi and Shinji Nagahiro : Predictability of the future development of aggressive behavior of cranial dural arteriovenous fistulas based on decision tree analysis., Journal of Neurosurgery, Vol.123, No.1, 86-90, 2015.
(Summary)
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.
Kenji Shimada, Hajime Furukawa, Kosuke Wada, Yuan Wei, Yoshiteru Tada, Atsushi Kuwabara, Fumiaki Shikata, Yasuhisa Kanematsu, Michael T. Lawton, Keiko T. Kitazato, Shinji Nagahiro and Tomoki Hashimoto : Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice, Journal of Cerebral Blood Flow and Metabolism, Vol.35, No.7, 1163-1168, 2015.
(Summary)
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.
(Keyword)
Aneurysm, Ruptured / Angiotensin I / Angiotensin II / Angiotensin II Type 2 Receptor Blockers / Animals / brain / Cerebral Arteries / cytokinesis / Imidazoles / Male / Mice / Mice, Inbred C57BL / knockout mice / Peptide Fragments / Pyridines / RNA, Messenger / Receptor, Angiotensin, Type 2 / Subarachnoid Hemorrhage
Satoshi Goto, Ryoma Morigaki, Shinya Okita, Shinji Nagahiro and Ryuji Kaji : Development of a highly sensitive immunohistochemical method to detect neurochemical molecules in formalin-fixed and paraffin-embedded tissues from autopsied human brains., Frontiers in Neuroanatomy, Vol.9, No.22, 2015.
(Summary)
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.
Takashi Abe, Yoshifumi Mizobuchi, Kohhei Nakajima, Youichi Otomi, Saho Irahara, Yuki Obama, Mungunkhuyag Majigsuren, Delgerdalai Khashbat, Teruyoshi Kageji, Shinji Nagahiro and Masafumi Harada : Diagnosis of brain tumors using dynamic contrast-enhanced perfusion imaging with a short acquisition time, SpringerPlus, Vol.24, No.4, 88, 2015.
(Summary)
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.
Norio Nakajima, Shinji Nagahiro, Junichiro Satomi, Yoshiteru Tada, Kohhei Nakajima, Shu Sogabe, Mami Hanaoka, Shunji Matsubara, Masaaki Uno and Koichi Satoh : Prevention of retrograde blood flow into large or giant internal carotid artery aneurysms by endovascular coil embolization with high-flow bypass: surgical technique and long-term results, World Neurosurgery, Vol.83, No.6, 1127-1134, 2015.
(Summary)
Recanalization has been reported in large or giant aneurysms of the internal carotid artery (ICA) addressed by high-flow bypass and endovascular treatment. Aneurysmal recanalization may be attributable to retrograde blood flow into the aneurysm through the ICA branches, such as the ophthalmic artery or the meningohypophyseal trunk, or through the surgically created bypass. We modified the endovascular treatment of aneurysms to prevent retrograde flow and evaluated the long-term efficacy of our method. We used a hybrid operative/endovascular technique to treat 5 patients with large or giant aneurysms arising from the C2-C4 segment of the ICA who presented with visual symptoms due to the mass effect of the aneurysm. To prevent retrograde flow into the aneurysm our modified endovascular treatment involves coil embolization of the aneurysmal orifice and the ICA, including the origin of the ophthalmic artery and meningohypophyseal trunk, and placement of a high-flow bypass using a radial artery graft. During the 5- to 12-year follow-up period, 4 aneurysms disappeared, and the other decreased in size. There were no subarachnoid hemorrhages. All bypass grafts remained patent. Visual preservation was achieved in 2 patients; 1 patient manifested visual improvement. Although 2 patients experienced transient neurological deficits we encountered no permanent complications in this series. The final modified Rankin scale of the 5 patients was 0 or 1. Prevention of retrograde flow into the aneurysm by coil embolization with high-flow bypass is a safe and effective method. It prevents the recanalization of large or giant ICA aneurysms.
Keijiro Hara, Teruyoshi Kageji, Yoshifumi Mizobuchi, Keiko T. Kitazato, Toshiyuki Okazaki, Toshitaka Fujihara, Kohhei Nakajima, Hideo Mure, Kazuyuki Kuwayama, Tomoyo Hara and Shinji Nagahiro : Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma, Cancer Letters, Vol.356, 496-505, 2015.
(Summary)
The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.
Shinji Nagahiro and Yoshifumi Mizobuchi : Visionary Approach to Sports Head Injury, Japanese Journal of Neurosurgery, Vol.23, No.12, 957-964, 2014.
(Summary)
We review current topics in sports-related head injuries including acute subdural hematoma (ASDH) and cerebral concussion. Sports-related ASDH is a leading cause of death and severe morbidity in popular contact sports like American football in the USA and judo in Japan. It is thought that rotational acceleration is most likely to produce not only cerebral concussion but also ASDH due to rupture of a parasagittal bridging vein, depending on the severity of the rotational acceleration injury. Repeated sports head injuries increase the risk for future concussion, cerebral swelling, or ASDH and chronic traumatic encephalopathy (CTE). To avoid fatal consequences or CTE resulting from repeated concussions, an understanding of the criteria for a safe post-concussion return to play is essential. Once diagnosed with a concussion, the athlete must not be allowed to return to play on the same day and should not resume play before the concussion symptoms have completely resolved. If brain damage has been confirmed or a subdural hematoma is present, the athlete should not be allowed to participate in any contact sports. Information on the risk for and management of head injuries in athletes participating in different sports should be widely disseminated in educational institutions and by public relations campaigns of sports organizations. Efforts must be made to educate not only personnel and parents directly involved in the care of athletes but also the general public.
(Keyword)
sports head injuries / acute subdural hematoma / concussion / sports head injuries / acute subdural hematoma / concussion
Nobuaki Yamamoto, Junichiro Satomi, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?, Clinical Neuroradiology, 2014.
(Summary)
The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.
Nobuaki Yamamoto, Junichiro Satomi, Yoshiteru Tada, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : The two-1 layered susceptibility vessel sign on 3-tesla T2*-weighted imaging is a predictive biomarker of stroke subtype, Stroke, Vol.46, No.1, 269-271, 2014.
(Summary)
A susceptibility vessel sign (SVS) on 1.5-tesla (T)-T2*-weighted images may predict cardioembolism. It has also been detected in patients with large artery atherosclerosis. In patients with major vessel occlusion, the SVS was comprised 2 layers on 3T-T2*-weighted images. We assessed the efficacy of 2-layered SVS on 3T-T2*-weighted imaging scans for predicting cardioembolism. Our study included 132 patients who had ischemic stroke within the preceding 24 hours and presented with internal carotid artery or middle cerebral artery occlusion because of cardioembolism or large artery atherosclerosis. We compared 2-layered SVS and SVS on 3T-T2*-weighted imaging scans for their sensitivity, specificity, and diagnostic odds ratio for predicting cardioembolism. We enrolled 132 patients (72 men; mean age, 74.5 years); of these, 63 (47.7%) were presented with cardioembolism. Although the sensitivity of SVS and 2-layered SVS for cardioembolism and large artery atherosclerosis was not statistically different (74.6% and 58.0%, respectively), the sensitivity of 2-layered SVS was significantly higher in patients with cardioembolism (42.9%) than those with large artery atherosclerosis (2.9%; P<0.001). The specificity and diagnostic odds ratio for 2-layered SVS for cardioembolism were 97.1% and 25.1; for SVS they were 42.0% and 2.1, respectively. The specificity of 2-layered SVS for cardioembolism was high. It may be useful for predicting cardioembolism and for the management of patients with acute ischemic stroke.
Yoshiteru Tada, Hiroshi Makino, Hajime Furukawa, Kenji Shimada, Kosuke Wada, EI Liang, Shoko Murakami, Mari Kudo, DK Kung, KT Kitazato, Shinji Nagahiro, MT Lawton and Tomoki Hashimoto : Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice, Neurosurgery, Vol.75, No.6, 690-695, 2014.
(Summary)
Epidemiological studies have indicated that postmenopausal women have a higher incidence of intracranial aneurysms than men in the same age group. To investigate whether estrogen or estrogen receptors (ERs) mediate protective effects against the formation of intracranial aneurysms. Intracranial aneurysms were induced in mice by combining a single injection of elastase into the cerebrospinal fluid with deoxycorticosterone acetate salt hypertension. The mice were treated with estrogen (17β-estradiol), an ERα agonist (propyl pyrazole triol), and an ERβ agonist (diarylpropionitrile) with and without a nitric oxide synthase inhibitor. The ovariectomized female mice had a significantly higher incidence of aneurysms than the male mice, which was consistent with findings in previous epidemiological studies. In ovariectomized female mice, an ERβ agonist, but not an ERα agonist or 17β-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERβ agonist was absent in the ovariectomized ERβ knockout mice. The protective effect of the ERβ agonist was negated by treatment with a nitric oxide synthase inhibitor. The effects of sex, menopause, and estrogen treatment observed in this animal study were consistent with previous epidemiological findings. Stimulation of estrogen receptor-β was protective against the formation of intracranial aneurysms in ovariectomized female mice.
Shinji Nagahiro and Yoshifumi Mizobuchi : Current topics in sports-related head injuries: A review, Neurologia Medico-Chirurgica, Vol.54, No.11, 878-886, 2014.
(Summary)
We review the current topic in sports-related head injuries including acute subdural hematoma (ASDH), concussion, and chronic traumatic encephalopathy (CTE). Sports-related ASDH is a leading cause of death and severe morbidity in popular contact sports like American football in the USA and judo in Japan. It is thought that rotational acceleration is most likely to produce not only cerebral concussion but also ASDH due to the rupture of a parasagittal bridging vein, depending on the severity of the rotational acceleration injury. Repeated sports head injuries increase the risk for future concussion, cerebral swelling, ASDH or CTE. To avoid fatal consequences or CTE resulting from repeated concussions, an understanding of the criteria for a safe post-concussion return to play (RTP) is essential. Once diagnosed with a concussion, the athlete must not be allowed to RTP the same day and should not resume play before the concussion symptoms have completely resolved. If brain damage has been confirmed or a subdural hematoma is present, the athlete should not be allowed to participate in any contact sports. As much remains unknown regarding the pathogenesis and pathophysiology of sports-related concussion, ASDH, and CTE, basic and clinical studies are necessary to elucidate the crucial issues in sports-related head injuries.
Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Sakai Waka, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : Predictors of neurologic deterioration in patients with small-vessel occlusion and infarcts in the territory of perforating arteries, Journal of Stroke & Cerebrovascular Diseases, Vol.23, No.8, 2151-2155, 2014.
(Summary)
It is difficult to predict neurologic deterioration in patients with small-vessel occlusion (SVO), that is, small infarcts in the territory of cerebral perforating arteries. We reviewed 110 patients with SVO who were admitted to our hospital. We divided them into groups with (n = 32, group 1) and without deterioration (n = 78, group 2) and evaluated their medical records, risk factors, magnetic resonance imaging findings, grade of periventricular hyperintensity (PVH), maximum diameter of the infarct area, and the number of slices showing infarcts on diffusion-weighted images (DWI). Our study population consisted of 110 patients (71 males and 39 females; mean age 69.2 years): 32 (29%) did and 78 (71%) did not suffer deterioration. By univariate analysis, the age, current smoking, history of stroke, maximum diameter of the infarcted area, number of DWI slices with infarcts, frequency of PVH, and PVH grade based on Fazekas classification differed significantly between the 2 groups. By multivariate analysis, conventional risk factors other than PVH and history of stroke were not associated with neurologic deterioration (PVH grade ≥ 2 versus PVH grade ≤ 1, odds ratio 6.72, P = .006; with stroke versus without stroke, odds ratio .21, P = .049). We also found that higher the PVH grade, the worse the National Institutes of Health Stroke Scale score at the time of discharge. PVH and without history of stroke are independently associated with neurologic deterioration in patients with SVO.
(Keyword)
Aged / Aged, 80 and over / Brain Infarction / Cerebral Arteries / Cerebral Ventricles / Diffusion Magnetic Resonance Imaging / Female / Humans / Intracranial Thrombosis / magnetic resonance imaging / Male / Middle Aged / Odds Ratio / Predictive Value of Tests / Risk Factors / smoking / PVH grade / neurologic deterioration / predictors / small vessel occlusion
Motohiro Hirasawa, Hideo Mure, Hiroyuki Toi and Shinji Nagahiro : Surgical results of lumbor interbody fusion using calcium phosphote cement, Neurologia Medico-Chirurgica, Vol.54, No.9, 722-726, 2014.
(Summary)
Clinical and radiological outcomes of lumbar interbody fusion using artificial fusion cages filled with calcium phosphate cements (CPCs) were retrospectively reviewed. Between 2002 and 2011, 25 patients underwent lumbar interbody fusion at Tokushima University Hospital, and 22 patients were enrolled in this study. Of these, 5 patients received autologous local bone grafts and 17 received CPC. Japan Orthopedic Association (JOA) score was used for clinical outcome assessments. Lumbar radiography and computed tomography (CT) were performed at 12, 24 months and last follow-up period to assess bony fusion. The mean JOA score of all patients improved from 9.3 before surgery to 21.0 at 24 months after surgery. Fusion had occurred in 5 of 5 patients in the local bone graft group and in 16 of 17 patients in CPC group at 24 months postoperatively. No surgically related complication was occurred in both groups. CPC is a useful and safe graft material for lumbar interbody fusion.
J Fujinami, T Uehara, K Kimura, Y Okada, Y Hasegawa, H Tanahashi, A Suzuki, S Takagi, J Nakagawara, K Arii, Shinji Nagahiro, K Ogasawara, T Nagao, S Uchiyama, M Matsumoto, K Iihara and K Minematsu : Incidence and predictors of ischemic stroke events during hospitalization in patients with transient ischemic attack, Cerebrovascular Diseases, Vol.37, No.5, 330-335, 2014.
(Summary)
The purpose of this study was to elucidate the incidence and predictors of ischemic stroke or recurrent transient ischemic attack (TIA) during acute hospitalization in patients with TIA. We carried out a multicenter retrospective study to clarify the characteristics of in-patients with TIA. The subjects of this study were TIA patients admitted to 13 stroke hospitals within 7 days after onset between 2008 and 2009. TIA was defined as focal neurologic symptoms ascribable to a vascular etiology lasting less than 24 h. We investigated the incidence and predictors of ischemic events including ischemic stroke or recurrent TIA during hospitalization. A total of 464 patients with TIA (292 men, 69 ± 13 years) were registered. Of those, 400 (86.2%) were admitted within 24 h of TIA onset. The mean length of hospital stay was 13 days. During hospitalization, 8 patients had ischemic strokes and 26 had recurrent TIAs. The leading subtype of 8 ischemic strokes was small vessel disease (n = 3) followed by cardioembolism (n = 2). Multiple logistic regression analysis showed that hypertension (OR: 3.41; 95% CI: 1.23-12.3), MRI-diffusion-weighted image positivity (OR: 2.49; 95% CI: 1.15-5.25), and hemiparesis (OR: 2.30; 95% CI: 1.02-5.88) were independently associated with ischemic events during hospitalization. In this study, 1.7% of patients with TIA had ischemic stroke during acute hospitalization, and the most common subtype was small vessel disease. Subsequent ischemic stroke and recurrent TIA were associated with hypertension, positive DWI findings, and hemiparesis.
(Keyword)
Adult / Aged / Aged, 80 and over / Diffusion Magnetic Resonance Imaging / Female / Hospitalization / Humans / Incidence / Ischemic Attack, Transient / Male / Middle Aged / Predictive Value of Tests / Retrospective Studies / Risk Factors / Stroke
Teruyoshi Kageji, Yoshifumi Mizobuchi, Shinji Nagahiro, Y Nagasawa and H Kumada : Correlation between rediatio dose and histopathological findings in patients with glioblastoma treated with boron neutron capture therapy (BNCT), Applied Radiation and Isotopes, Vol.88, 20-22, 2014.
(Summary)
The purpose of this study was to clarify the correlation between the radiation dose and histopathological findings in patients with glioblastoma multiforme (GBM) treated with boron neutron capture therapy (BNCT). Histopathological studies were performed on specimens from 8 patients, 3 had undergone salvage surgery and 5 were autopsied. For histopathological cure of GBM at the primary site, the optimal minimal dose to the gross tumor volume (GTV) and the clinical target volume (CTV) were 68Gy(w) and 44Gy(w), respectively.
Teruyoshi Kageji, Shinji Nagahiro, Junichiro Satomi, Yuka Terasawa and Masafumi Harada : Evolution of Stroke Emergency System in Tokushima University Hospital, Japanese Journal of Stroke, Vol.36, No.3, 223-229, 2014.
(Summary)
We established the stroke care unit (SCU) for stroke emergency system in Tokushima University Hospital. There were 3,452 patients admitted with acute stroke from 1999 to 2013 in our institute, and 131 patients with acute ischemic stroke were treated with rt-PA (recombinant tissue-type plasminogen activator) intravenous infusion therapy. Revascularization therapy for acute ischemic stroke was done in 20% of patients and rt-PA intravenous infusion therapy in 10.6% of patients. SCU was on track since 2008 and the implementation rate of therapy during this period was 12.8%. The activity of stroke center in our institute promotes improvement of stroke medical level in the region, increase of convalescence rehabilitation facility, and increase in the hospital medical fees. As a result, the stroke center has contributed to medical students and young doctors for the education of stroke. Challenge for the future is the establishment of the treatment system for acute stroke in the medical depopulated area.
Susumu Miyamoto, Takashi Yoshimoto, Nobuo Hashimoto, Yasushi Okada, Ichiro Tsuji, Teiji Tominaga, Jyoji Nakagawara, C Jun Takahashi, K yamada, Y Tomata, T Fukui, Y Fukuuchi, T Ohmoto, Y Kuwabara, Y Nagata, J Ono, T Machida, R Sakakibara, K Yamane, S Okita, T Iwama, Y Kaku, N Saito, H Fukuyama, K Houkin, S Kuroda, I Yabe, F Moriwaka, A Ogawa, K Ogasawara, K Yoshida, K Fuji, M Yamada, K Sato, S Yamagata, S Takeuchi, K Hayashi, N Horie, K Yamada, T Osato, T Watanabe, K Honjo, K Sako, H Nakase, S Kawaguchi, S Nishimura, J Yamano, H Naritomi, T Inoue, H Abe, A Suzuki, T Ishikawa, Y Akiyama, T Suenaga, M Fujimura, Shinji Nagahiro, Masaaki Uno, Kyoko Nishi, Junichiro Satomi, Y Okada, A Kawashima, K Yamaguchi and Y Tsutsumi : Effect of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease - Results of the Japan adult moyamoya trial-, Stroke, Vol.45, No.5, 1415-1421, 2014.
(Summary)
About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial-intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial-intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan-Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P=0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148-1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan-Meier survival analysis (2.7%/y versus 7.6%/y; P=0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125-1.009). Although statistically marginal, Kaplan-Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000166.
N Etminan, K Beseoglu, DL Barrow, J Bedersonn, Jr RD Brown, Jr ES Connolly, CP Derdeyn, D Hnggi, D Hasan, S Juvela, H Kasuya, PJ Kirkpatrick, N Knuckey, T Koivisto, G Lanzino, MT Lawton, P LeRoux, CG McDougall, E Mee, J Mocco, A Molyneux, MK Morgan, K Mori, A Morita, Y Murayama, Shinji Nagahiro, A Pasqualin, A Raabe, J Raymond, GJE Rinkel, D fenacht R, V Seifert, J Spears, HJ Steiger, H Steinmetz, JC Torner, P Vajkoczy, I Wanke, GKC Wong, JH Wong and RL MacDonald : Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: Proposal of an international research group, Stroke, Vol.45, No.5, 1523-1530, 2014.
(Summary)
To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.
Yoshiteru Tada, K Wada, Kenji Shimada, H Makino, EI Liang, S Murakami, M Kudo, F Shikata, RAP Silva, KT Kitazato, DM Hasan, Yasuhisa Kanematsu, Shinji Nagahiro and T Hashimoto : Estrogen protects against intracranial aneurysm rupture in ovariectomized mice, Hypertension, Vol.63, 1339-1344, 2014.
(Summary)
Clinical observations suggest that postmenopausal women have a higher incidence of aneurysmal rupture than premenopausal women. We hypothesize that a relative deficiency in estrogen may increase the risks of aneurysmal growth and subarachnoid hemorrhage in postmenopausal women. We assessed the effects of estrogen and selective estrogen receptor subtype agonists on the development of aneurysmal rupture in ovariectomized female mice. We used an intracranial aneurysm mouse model that recapitulates the key features of human intracranial aneurysms, including spontaneous rupture. Ten- to 12-week-old ovariectomized female mice received treatment with estrogen, nonselective estrogen receptor antagonist, estrogen receptor-α agonist, or estrogen receptor-β agonist starting 6 days after aneurysm induction so that the treatments affected the development of aneurysmal rupture without affecting aneurysmal formation. Estrogen significantly reduced the incidence of ruptured aneurysms and rupture rates in ovariectomized mice. Nonselective estrogen receptor antagonist abolished the protective effect of estrogen. Although estrogen receptor-α agonist did not affect the incidence of ruptured aneurysms or rupture rates, estrogen receptor-β agonist prevented aneurysmal rupture without affecting the formation of aneurysms. The protective role of estrogen receptor-β agonist was abolished by the inhibition of nitric oxide synthase. We showed that estrogen prevented aneurysmal rupture in ovariectomized female mice. The protective effect of estrogen seemed to occur through the activation of estrogen receptor-β, a predominant subtype of estrogen receptor in human intracranial aneurysms and cerebral arteries.
Toshiyuki Okazaki, Y Yamamoto, K Yoda and Shinji Nagahiro : The ratio of D-dimer to brain natriuretic peptide may help to differentiate between cerebral infarction with and without acute aortic dissection, Journal of the Neurological Sciences, Vol.340, No.1-2, 133-138, 2014.
(Summary)
Previous studies reported that the plasma d-dimer level reflects the activity of thrombus formation in the left atrium of patients with acute cerebral infarction and acute aortic dissection (AAD). Brain natriuretic peptide (BNP) is considered to be a marker of chronic heart failure. The differential diagnosis in the emergency room between stroke due to cardioembolism and AAD is difficult but important for early treatment especially in patients requiring intravenous thrombolysis with a recombinant tissue-type plasminogen activator. We aimed to investigate the association between the plasma d-dimer and BNP levels in patients with cerebral infarction and AAD. We identified 115 consecutive patients with ischemic stroke who were admitted within 72 h of symptom onset and 15 consecutive patients with AAD and measured the level of plasma d-dimer and BNP and the d-dimer:BNP ratio. In patients with AAD the d-dimer level was significantly higher than that in patients with any other stroke subtypes and their BNP level was significantly lower than that in patients with cardioembolic stroke. The d-dimer:BNP ratio was significantly higher in patients with AAD than in those with any other stroke subtype. Compared to patients with a cardioembolic stroke subtype they manifested significantly higher d-dimer levels and d-dimer:BNP ratios suggesting that this ratio may help to diagnose cerebral infarction due to AAD (sensitivity 80%, specificity 93.5%, cut-off 0.074). When the population was limited to patients within 6h of onset, the ratio had higher sensitivity and specificity at the same cut-off value (sensitivity 81.8%, specificity 96.4%). We found that the d-dimer:BNP ratio may be helpful in distinguishing between cerebral infarction with and without AAD.
Koji Tanaka, Toshiyuki Uehara, Kazumi Kimura, Yasushi Okada, Yasuhiro Hasegawa, Norio Tanahashi, Akifumi Suzuki, Shigeharu Takagi, Jyoji Nakagawara, Kazumasa Arii, Shinji Nagahiro, Kuniaki Ogasawara, Takehiko Nagao, Shinichiro Uchiyama, Masayasu Matsumoto, Koji Iihara, Kazunori Toyoda and Kazuo Minematsu : Features of patients with transient monocular blindness: a multicenter retrospective study in Japan, Journal of Stroke & Cerebrovascular Diseases, Vol.23, 151-154, 2014.
(Summary)
Transient monocular blindness (TMB) is associated with a transient ischemic attack (TIA). The purpose of this study was to investigate the features of TMB in the Japanese population using data from a multicenter retrospective study of TIA. The subjects were consecutive TIA patients admitted to 13 stroke centers within 7 days after symptom onset. We compared clinical characteristics of patients with TMB and those without TMB who had other symptoms of cerebral TIA. A total of 464 patients were registered between January 2008 and December 2009, and 444 patients (283 men, mean age: 68.5 years) were included in the analysis. Thirteen patients (2.9%) presented with TMB. Patients with TMB were less likely to arrive at the specialized stroke center quickly than those without TMB (P = .013). Stenotic lesions in the extracranial internal carotid artery were more common in patients with TMB (33.3% versus 9.1%, P = .022). TMB was not common in our TIA inpatients. This study suggests that patients with TMB should immediately undergo a diagnostic workup, including brain and vessel imaging, and cardiac evaluation, as is performed in patients with other cerebral TIA symptoms. A larger, prospective cohort is needed to confirm the risks and outcomes of patients with TMB in the Japanese population.
(Keyword)
Aged / Aged, 80 and over / Amaurosis Fugax / diagnostic imaging / Female / Humans / Ischemic Attack, Transient / Japan / Male / Middle Aged / Patient Admission / Predictive Value of Tests / Prognosis / Retrospective Studies / Risk Assessment / Risk Factors / Time-to-Treatment / Transportation of Patients
Yoshiteru Tada, Junichiro Satomi, Takashi Abe, Kazuyuki Kuwayama, Shu Sogabe, Koji Fujita, Nobuaki Yamamoto, Ryuji Kaji, Masafumi Harada and Shinji Nagahiro : Intra-arterial signal on arterial spin labeling perfusion MRI to identify the presence of acute middle cerebral artery occlusion, Cerebrovascular Diseases, Vol.38, No.3, 191-196, 2014.
(Summary)
The susceptibility vessel sign on gradient echo-type-T2*-weighted imaging is a well-known marker of arterial occlusion. Stagnant flow in front of the middle cerebral artery (MCA) occlusion sites may contribute to the intra-arterial, high-intensity signal on arterial spin labeling magnetic resonance imaging (MRI), making it another potential marker of MCA occlusion. We compared the intra-arterial, high-intensity signal and susceptibility vessel sign in patients with symptomatic MCA occlusion and patients without major vessel occlusion. We identified transient ischemic attack or ischemic stroke patients with (1) 3-T MRI performed within 24 h after clinical onset including arterial spin labeling, T2*-weighted imaging, and magnetic resonance angiography (MRA) and (2) either having MCA occlusion (n = 34 patients) or without major vessel occlusion (n = 24 patients). The intra-arterial, high-intensity signal was defined as an enlarged circular or linear bright hyperintensity within the artery. The susceptibility vessel sign was defined as an enlarged spot of hypointensity within the MCA, in which the diameter of the hypointense signal within the vessel exceeded the contralateral vessel diameter. The presence or absence of the intra-arterial, high-intensity signal and susceptibility vessel sign were assessed, along with their inter-rater agreement and consistency with the presence of MCA occlusion on MRA. The intra-arterial, high-intensity signal was detectable in 30 patients (52%), and susceptibility vessel sign was observed in 17 patients (29%). The sensitivity of the intra-arterial high-intensity signal was significantly higher than that of the susceptibility vessel sign (88% vs. 50%; p < 0.05). The accuracy of the intra-arterial high-intensity signal was also higher than that of the susceptibility vessel sign (93% vs. 71%; p < 0.05). The intra-arterial high-intensity signal was situated in the proximal regions of the susceptibility vessel sign on T2*WI within the MCA. Neither the intra-arterial high-intensity signal nor the susceptibility vessel sign was observed in patients without major vessel occlusion. Inter-rater agreement was good for intra-arterial high-intensity signal detection (κ = 0.73) and moderate for susceptibility vessel sign detection (κ = 0.47). The presence or absence of the intra-arterial high-intensity signal was highly consistent with that of MCA occlusion on MRA (κ = 0.74). The intra-arterial high-intensity signal on arterial spin labeling appears to be useful to identify the presence of acute MCA occlusion and may be associated with stagnant flow in front of occlusion sites. The intra-arterial high-intensity signal may also be used to identify the occlusion site.
(Keyword)
Aged / Aged, 80 and over / Cerebral Angiography / Female / Humans / Infarction, Middle Cerebral Artery / Ischemic Attack, Transient / Magnetic Resonance Angiography / magnetic resonance imaging / Male / Middle Aged / Middle Cerebral Artery / Sensitivity and Specificity / Stroke
Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : Reversibility of ischemic findings on 3-tesla magnetic resonance T2(*)-weighted image after recanalization, The Journal of Medical Investigation : JMI, Vol.61, No.1,2, 190-196, 2014.
(Summary)
Ischemic vessel signs (IVS) can be detected on 3-tesla T2(*)-weighted magnetic resonance images as a vessel enlargement at the territory of acute ischemia caused by major vessel occlusion or stenosis. Here, we studied changes in IVS before and after recanalization by the administration of intravenous recombinant tissue plasminogen activator (IV rtPA), carotid artery stenting or percutaneous transluminal angioplasty in patients with major vessel occlusion or stenosis. We performed magnetic resonance imaging for all patients treated by IV rtPA at the time of admission, shortly after and 24-72 hours after treatment with IV rtPA. We reviewed the IVS to assess its natural course of IVS by assessing patients who did not recanalize. IVS tended to disappear after recanalization. Conversely, in patients without recanalization, IVS did not disappear shortly after IV rtPA; rather, it disappeared 24-72 hours after IV rtPA, especially in the presence of complete infarction. Recanalization by IV rtPA or endovascular treatment contributed to improved clinical deficits or the prevention from further progression. IVS can be a parameter of misery perfusion and an important factor to detect the patients who have an indication of treatment for recanalization.
Toshiyuki Uehara, Kazumi Kimura, Yasushi Okada, Yasuhiro Hasegawa, Norio Tanahashi, Akifumi Suzuki, Shigeharu Takagi, Jyoji Nakagawara, Kazumasa Arii, Shinji Nagahiro, Kuniaki Ogasawara, Takehiko Nagao, Shinichiro Uchiyama, Masayasu Matsumoto, Koji Iihara, K Toyoda and Koji Minematsu : Factors associated with onset-to-door time in patients with transient ischemic attack admitted to stroke centers, Stroke, Vol.45, No.2, 611-613, 2014.
(Summary)
The aim of this study was to elucidate the factors associated with the time from symptom onset to arrival at a stroke center (onset-to-door time [ODT]) in patients with classically defined transient ischemic attack using data from a multicenter, retrospective study. The subjects were patients with transient ischemic attack admitted to 13 stroke centers in Japan within 7 days of onset between 2008 and 2009. A total of 464 patients registered (292 men, 68.5±13.2 years old), and 421 of them (268 men, 68.8±13.1 years old) were included in the analyses. ODT was classified into the following 5 categories: <3 hours, 3 to 6 hours, 7 to 12 hours, 13 to 24 hours, and >24 hours. There were 233 patients (55.3%) who visited a stroke center within 3 hours of symptom onset. Multiple ordinal logistic regression analysis revealed that motor weakness, speech disturbance, and duration of symptoms >10 minutes were independently associated with a short ODT. Furthermore, a history of transient ischemic attack and hypertension and a referral from another medical facility were independently associated with a long ODT. Patients with a higher ABCD2 score were likely to arrive at a stroke center more quickly. We identified several factors that were positively and negatively associated with the ODT in patients with transient ischemic attack.
(Keyword)
Aged / Aged, 80 and over / Emergency Medical Services / Female / Hospital Units / Humans / hypertension / Ischemic Attack, Transient / Japan / Logistic Models / Male / Middle Aged / Muscle Weakness / Referral and Consultation / Retrospective Studies / Speech Disorders / Stroke / Time Factors / Treatment Outcome
Yoshiteru Tada, Wada Kosuke, Kenji Shimada, Makino Hiroshi, EI Liang, Murakami Shoko, Kudo Mari, KT Kitazato, Shinji Nagahiro and Hashimoto Tomoki : Roles of hypertension in the rupture of intracranial aneurysms, Stroke, Vol.45, No.2, 579-586, 2014.
(Summary)
Systemic hypertension has long been considered a risk factor of aneurysmal rupture. However, a causal link between systemic hypertension and the development of aneurysmal rupture has not been established. In this study, using a mouse model of intracranial aneurysm rupture, we examined the roles of systemic hypertension in the development of aneurysmal rupture. Aneurysms were induced by a combination of deoxycorticosterone acetate (DOCA)-salt and a single injection of elastase into the cerebrospinal fluid in mice. Antihypertensive treatment was started 6 days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysm with subarachnoid hemorrhage. Hydralazine (direct vasodilator) or discontinuation of DOCA-salt treatment was used to assess the roles of systemic hypertension. Captopril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin II type 1 receptor antagonist) was used to assess the roles of the local renin-angiotensin system in the vascular wall. Normalization of blood pressure by hydralazine significantly reduced the incidence of ruptured aneurysms and the rupture rate. There was a dose-dependent relationship between reduction of blood pressure and prevention of aneurysmal rupture. Captopril and losartan were able to reduce rupture rate without affecting systemic hypertension induced by DOCA-salt treatment. Normalization of blood pressure after aneurysm formation prevented aneurysmal rupture in mice. In addition, we found that the inhibition of the local renin-angiotensin system independent from the reduction of blood pressure can prevent aneurysmal rupture.
Toshiyuki Okazaki, Teruyoshi Kageji, Yoshifumi Mizobuchi, Takeshi Miyamoto and Shinji Nagahiro : Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma: A case report,, Applied Radiation and Isotopes, Vol.88, 28-31, 2014.
(Summary)
Boron neutron capture therapy (BNCT) has been reported to be effective in the patients with glioblastoma multiforme (GBM). Median survival time (MST) of GBM patients treated with BNCT is approximately two years. GBM patients surviving 2 or 3 years are considered long-term survivors. In general, most recurrences are local and dissemination is rare. We report an unusual patient with three recurrences; the first and the second recurrences were local, and the third recurrence was dissemination nine years after BNCT.
Junichiro Satomi, Yoshiteru Tada, Kenji Yagi, Nobuhisa Matsushita, Nobuaki Yamamoto, Yasuhisa Kanematsu and Shinji Nagahiro : Treatment Outcomes in Patients Older than 80 Years Presenting with Ruptured Intracranial Aneurysms, Surgery for Cerebral Stroke, Vol.42, No.1, 42-46, 2014.
(Summary)
While the number of elderly patients who presented with aneurysmal subarachnoid hemorrhage (SAH) has been increasing, its optimal management in that population remains controversial. Therefore, we retrospectively reviewed the treatment outcomes in 49 consecutive patients aged between 80 and 94 years who presented with SAH. The neurological World Federation of Neurological Surgeons (WFNS) grade at the time of admission was Grade I in 7, Grade II in 11, Grade III in 8, Grade IV in 13, and Grade V in 10 patients. Of the 49 patients, 28 underwent coil embolization, and 7 (25%) had a favorable outcome (mRS: 0-2) at discharge, while in 21 (75%) the outcome was poor (mRS: 3-6). Six patients underwent clipping; the outcome was favorable in one patient (17%) and poor in 5 (83%). Of 15 patients under conservative therapy none had a favorable outcome. A low WFNS grade (I-II) was significantly associated with a favorable outcome (p<0.05). Although the treatment outcome in elderly patients with SAH was poor, radical treatment of ruptured aneurysms should be considered if their WFNS grade is low.
Yuka Terasawa, Nobuaki Yamamoto, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Junichiro Satomi, Masafumi Harada, Shinji Nagahiro and Ryuji Kaji : Brush sign on 3-T t2*-weighted MRI as a potential predictor of hemorrhagic transformation after tissue plasminogen activator therapy, Stroke, Vol.45, No.1, 274-276, 2014.
(Summary)
The brush sign (BS) is the enlargement of medullary veins on 3-T T2*-weighted MRI seen in patients with ischemic stroke because of major cerebral artery occlusion. However, the clinical relevance of BS in patients with acute stroke remains unclear. We assessed the correlation between detecting BS with the development of hemorrhagic transformation after intravenous thrombolysis. We enrolled consecutive patients with M1 or M2 occlusion treated with intravenous tissue plasminogen activator. We classified the patients into 2 groups: the group positive for BS (P-BS) and the group negative for BS (N-BS). We investigated the differences in MRI findings and the clinical outcome between the 2 groups. The subjects consisted of 36 patients (19 men; mean age, 74.7 years). Twenty-one patients (58%) had M1 occlusion, and 15 (42%) had M2 occlusion. Twenty-five patients (69%) were classified into the P-BS group and 11 (31%) into the N-BS group. Recanalization was observed in 15 (60%) and 10 (90%) patients in the P-BS and N-BS groups, respectively (P=0.116). Hemorrhagic transformation on MRI was observed more frequently in the P-BS group than in the N-BS group (64% versus 18%; P=0.027). A good outcome (mRS, 0-1) at discharge was found in 24% of patients in the P-BS group and in 45% of patients in the N-BS group (P=0.152). A multivariate logistic regression analysis revealed that the presence of BS (odds ratio, 9.08; 95% confidence interval, 1.4-59.8; P=0.022) was independently associated with hemorrhagic transformation. BS may predict the development of hemorrhagic transformation in patients with acute stroke treated with intravenous tissue plasminogen activator.
Teruyoshi Kageji, Shinji Nagahiro, Yoshifumi Mizobuchi, Kazuhito Matsuzaki, Y Nagasawa and H Kumada : Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment, The Journal of Medical Investigation : JMI, Vol.61, No.3-4, 254-263, 2014.
(Summary)
The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.
Shunji Matsubara, Koichi Satoh, Junichiro Satomi, Toshio Shigekiyo, Tomoya Kinouchi and Shinji Nagahiro : Acquired pial and dural arteriovenous fistulae following superior sagittal sinus theombosis in patients with protein S deficiency: A report of two cases, Neurologia Medico-Chirurgica, Vol.54, No.3, 245-252, 2014.
(Summary)
Two patients with protein S deficiency with acquired multiple pial and dural arteriovenous fistulae (AVFs) following superior sagittal sinus (SSS) thrombosis are reported. Case 1 is a 38-year-old male with protein S deficiency who developed generalized seizure due to SSS thrombosis. Local fibrinolysis was achieved in the acute stage. His 10-month follow-up angiogram revealed an asymptomatic acquired dural AVF arising from the middle meningeal artery and the anterior cerebral artery with drainage to the thrombosed cortical vein in the right frontal lobe. Furthermore, his 2-year follow-up angiogram revealed a de novo pial AVF from the middle cerebral artery in the Sylvian fissure with drainage to the cortical vein initially thrombosed. However, this asymptomatic pial AVF caused bleeding in the ipsilateral cerebral hemisphere 12 years after onset, whereas the dural AVF spontaneously disappeared. Surgical disconnection was successfully performed to eliminate the source of hemorrhage. Case 2 is a 50-year-old male with a past history of SSS thrombosis with protein S deficiency who developed pulsatile tinnitus and generalized seizure. His angiogram showed a cortical dural AVF in the left parietal lobe and a sporadic dural AVF involving the right sigmoid sinus. The parietal lesion was eliminated by transarterial embolization followed by craniotomy. However, a de novo pial AVF emerged from the middle cerebral artery adjacent to the previously treated lesion. Of four cortical AVFs in two patients, thrombosis of cortical veins caused by protein S deficiency might play an important role in their formation. Long-term follow-up is required because this peculiar disorder has an unusual clinical course.
(Keyword)
Adult / Central Nervous System Vascular Malformations / Cerebral Angiography / Combined Modality Therapy / Craniotomy / Embolization, Therapeutic / Humans / Magnetic Resonance Angiography / Male / Middle Aged / Pia Mater / Protein S Deficiency / Sagittal Sinus Thrombosis / Thrombolytic Therapy / Urokinase-Type Plasminogen Activator
Teruyoshi Kageji, Hirofumi Oka, Shinji Nagahiro, Junichiro Satomi, Yoshifumi Mizobuchi, Kenji Tani, Mitsuhiro Kohno, Shino Yuasa, Ryo Tabata, Hiroyashu Bando, 森 敬子, 小幡 史明, 三橋 乃梨子, 浦岡 秀行 and 濱口 隼人 : Introduction of Tokushima Prefectural Kaifu Hospital telemedicine support system (k-support) using a smartphone and the Internet, Shikoku Acta Medica, Vol.69, No.5-6, 243-250, 2013.
(Summary)
Because a specialist in general medical treatment lacked the Kaifu area of South Tokushima absolutely, we forced a limited doctor to many burdens and performed medical treatment while I always carried risks on my back for the disease except the specialty domain. A stroke specialist in particular is an absent medical depopulated area, and it is difficult to perform the rt-PA IV therapy that is a standard therapy for a stroke for the immediate nature period. Using remote video diagnosis treatment supporting system SYNAPSE ERm that was the smartphone application that FUJIFILM developed for the purpose of canceling these, we introduced smartphone and Tokushima Prefectural Kaifu Hospital remoteness medical treatment support system (k-support) by the Internet as area medical treatment support in February, 2013. This system can provide image information and patient information such as CT or the MRI to a tablet phone and the smartphone of Tokushima Prefectural Kaifu Hospital full-time employment doctors and the doctors who support it, and work in a House in real time. In other words, we can obtain necessary information without asking the when and where and can send appropriate instructions, advice to the Tokushima Prefectural Kaifu Hospital medical attendant from a specialist for it. After introduction, the treatment with this system in 58 emergency patients was carried out in seven months until August 31. The example letting the wide area present the smartphone such as this system and a remote medical treatment support system using the Internet in the medical depopulated area is the first trial in this country.
Junichiro Satomi and Shinji Nagahiro : Pathogenesis and Natural History of Brain Arteriovenous Malformation and Dural Arteriovenous Fistula, Japanese Journal of Neurosurgery, Vol.22, No.12, 898-903, 2013.
Yoshitaka Kurashiki, Teruyoshi Kageji, Yoshifumi Mizobuchi, Junichiro Satomi, Koichi Satoh, Takanori Hirose and Shinji Nagahiro : [Differential diagnosis of and therapy for anaplastic astroblastoma: case report and review of the literature]., Neurological Surgery, Vol.41, No.10, 891-899, 2013.
(Summary)
Astroblastomas are rare glial tumors. We report a case of 33-year-old woman with high-grade astroblastoma with hypervascularity. She had a one-month history of right visual disturbance and papillar edema. MRI revealed a lobulated mass with cysts and flow voids in the right superficial frontal lobe, a phenomenon described as "bubbly appearance". Right carotid angiography demonstrated marked tumor stain and early venous filling. MR spectroscopy showed an increase in myoinositol and the choline/creatine ratio, and decreased N-acetyl aspartate. The lipid and lactate level was not increased. The well-circumscribed tumor was totally resected. Histological examination showed perivascular pseudorosettes and hyalinization of blood vessels with high cellularity, anaplastic nuclear features, focal necrosis, mitosis, and endothelial proliferation. Immunohistochemically, glial fibrillary acidic protein and S-100 protein were intensely positive and the MIB-1 labeling index was high(20%)in the tumor cells. Based on these findings, a diagnosis of high-grade astroblastoma was made. The patient received postoperative radiotherapy and chemotherapy with temozolomide and suffered no relapse in the course of 3 years after surgery. Characteristically, astroblastomas manifest a "bubbly appearance" and a lobulated mass on MRI scans. As these tumors tend to be hypervascular, angiograms are useful for designing the operative strategy. However, their low-or high grade is difficult to ascertain preoperatively based on MRI-, MRS-, and DSA findings. The standard therapy for high-grade astroblastoma is total resection and postoperative radiation therapy. As the incidence of tumor recurrence is high, we recommend additional chemotherapy with TMZ.
Takeshi Kamitani, Yuji Nimura, Shinji Nagahiro, Seiji Miyazaki and Taisuke Tomatsu : Catastrophic head and neck injuries in Judo players in Japan from 2003 to 2010, The American Journal of Sports Medicine, Vol.41, No.8, 1915-1921, 2013.
(Summary)
Few studies have documented catastrophic head and neck injuries in judo, but these injuries deserve greater attention. To determine the features of catastrophic head and neck injuries in judo. Descriptive epidemiological study. This study was based on the accident reports submitted to the All Japan Judo Federation's System for Compensation for Loss or Damage. A total of 72 judo injuries (30 head, 19 neck, and 23 other injuries) were reported between 2003 and 2010. The investigated parameters were mechanism of injury, age at time of injury, length of judo experience, diagnosis, and outcome. Among head injuries, 27 of 30 (90%) occurred in players younger than 20 years of age. The relationship between age, mechanism, and location of injury was more relevant when players younger than 20 years incurred head injury while being thrown (P = .0026). Among neck injuries, 13 of 19 (68%) occurred in players with more than 36 months of experience. The relationship between experience, mechanism, and location of injury was more relevant when experienced players incurred neck injury while executing an offensive maneuver (P = .0294). Acute subdural hematoma was diagnosed in 94% of head injuries. The outcomes of head injury were as follows: 15 players died; 5 were in a persistent vegetative state; 6 required assistance because of higher brain dysfunction, hemiplegia, or aphasia; and 4 had full recovery. Among neck injuries, 18 players were diagnosed with cervical spine injury, 11 of whom had fracture-dislocation of the cervical vertebra; there was also 1 case of atlantoaxial subluxation. The outcomes of neck injury were as follows: 7 players had complete paralysis, 7 had incomplete paralysis, and 5 had full recovery. Neck injuries were associated with having more experience and executing offensive maneuvers, whereas head injuries were associated with age younger than 20 years and with being thrown.
(Keyword)
Adolescent / Adult / Age Distribution / Aged / Child / Craniocerebral Trauma / Female / Humans / Incidence / Japan / Male / Martial Arts / Middle Aged / Neck Injuries / Retrospective Studies / Risk Factors / Treatment Outcome / Young Adult
Kohhei Nakajima, Yoichi Maekawa, Keiko Kataoka, Chieko Ishifune, Jun Nishida, Hideki Arimochi, Akiko Kitamura, Takayuki Yoshimoto, Shuhei Tomita, Shinji Nagahiro and Koji Yasutomo : The ARNT-STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ+CD8αα+cells., Nature Communications, Vol.4, 2112, 2013.
(Summary)
Intestinal intraepithelial T cells contribute to the regulation of inflammatory responses in the intestine; however, the molecular basis for their development and maintenance is unknown. The aryl hydrocarbon receptor complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and senses environmental factors, including gut microbiota. Here, we identify ARNT as a critical regulator of the differentiation of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells. Mice deficient in either ARNT or aryl hydrocarbon receptor show a greater than- eight-fold reduction in the number of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells. The number of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells is increased by treatment with an aryl hydrocarbon receptor agonist in germ-free mice and is decreased by antibiotic treatment. The Arnt-deficient precursors of TCRαβ(+)CD8αα(+) intestinal intraepithelial T cells express low amounts of STAT3 and fail to differentiate towards the TCRαβ(+)CD8αα(+) cell fate after IL-15 stimulation, a deficiency that is overcome by overexpression of Stat3. These data demonstrate that the ARNT-STAT3 axis is a critical regulator of TCRαβ(+)CD8αα(+) intestinal intraepithelial T-cell development and differentiation.
Hidetaka Koizumi, Ryoma Morigaki, Shinya Ohkita, Shinji Nagahiro, Masanori Nakagawa and Satoshi Goto : Response of striosomal opioid signaling to dopamine depletion in 6-hydroxydopamine-lesioned rat model of Parkinsons disease: a potential compensatory role, Frontiers in Cellular Neuroscience, Vol.7, 74, 2013.
(Summary)
The opioid peptide receptors consist of three major subclasses, namely, μ, δ, and κ (MOR, DOR, and KOR, respectively). They are involved in the regulation of striatal dopamine functions, and increased opioid transmissions are thought to play a compensatory role in altered functions of the basal ganglia in Parkinson's disease (PD). In this study, we used an immunohistochemistry with tyramide signal amplification (TSA) protocols to determine the distributional patterns of opioid receptors in the striosome-matrix systems of the rat striatum. As a most striking feature of striatal opioid anatomy, MORs are highly enriched in the striosomes and subcallosal streak. We also found that DORs are localized in a mosaic pattern in the dorsal striatum (caudate-putamen), with heightened labeling for DOR in the striosomes relative to the matrix compartment. In the 6-hydroxydopamine-lesioned rat model of PD, lesions of the nigrostriatal pathways caused a significant reduction of striatal labeling for both the MOR and DOR in the striosomes, but not in the matrix compartment. Our results suggest that the activities of the striosome and matrix compartments are differentially regulated by the opioid signals involving the MORs and DORs, and that the striosomes may be more responsive to opioid peptides (e.g., enkephalin) than the matrix compartment. Based on a model in which the striosome compartment regulates the striatal activity, we propose a potent compensatory role of striosomal opioid signaling under the conditions of the striatal dopamine depletion that occurs in PD.
Satoshi Goto, Toshitaka Kawarai, Ryoma Morigaki, Shinya Okita, Hidetaka Koizumi, Shinji Nagahiro, L Edwin Munoz, V Lillian Lee and Ryuji Kaji : Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism., Brain, Vol.136, No.Pt 5, 1555-1567, 2013.
(Summary)
Neuropeptide Y is a novel bioactive substance that plays a role in the modulation of neurogenesis and neurotransmitter release, and thereby exerts a protective influence against neurodegeneration. Using a sensitive immunohistochemical method with a tyramide signal amplification protocol, we performed a post-mortem analysis to determine the striatal localization profile of neuropeptide Y in neurologically normal individuals and in patients with X-linked dystonia-parkinsonism, a major representative of the neurodegenerative diseases that primarily involve the striatum. All of the patients examined were genetically verified as having X-linked dystonia-parkinsonism. In normal individuals, we found a scattered distribution of neuropeptide Y-positive neurons and numerous nerve fibres labelled for neuropeptide Y in the striatum. Of particular interest was a differential localization of neuropeptide Y immunoreactivity in the striatal compartments, with a heightened density of neuropeptide Y labelling in the matrix compartment relative to the striosomes. In patients with X-linked dystonia-parkinsonism, we found a significant decrease in the number of neuropeptide Y-positive cells accompanied by a marked loss of their nerve fibres in the caudate nucleus and putamen. The patients with X-linked dystonia-parkinsonism also showed a lack of neuropeptide Y labelling in the subventricular zone, where a marked loss of progenitor cells that express proliferating cell nuclear antigen was found. Our results indicate a neostriatal defect of the neuropeptide Y system in patients with X-linked dystonia-parkinsonism, suggesting its possible implication in the mechanism by which a progressive loss of striatal neurons occurs in X-linked dystonia-parkinsonism.
Naomi Morita, Masafumi Harada, Junichiro Satomi, Yuka Terasawa, Ryuji Kaji and Shinji Nagahiro : Frequency of emerging positive diffusion-weighted imaging in early repeat examinations at least 24 h after transient ischemic attacks, Neuroradiology, Vol.55, No.4, 399-403, 2013.
(Summary)
The relationships between diffusion lesions and risk scores for patients with a Transient ischemic attack (TIA) and the optimal timing for diffusion lesion screening have not been characterized. The purpose of our study was to evaluate the appearance of diffusion-weighted imaging (DWI) lesions during follow-up examinations of patients with TIA or minor stroke without initial DWI lesions. We identified 31 patients who did not show diffusion lesions in initial DWI. A second magnetic resonance imaging (MRI) examination was performed 24 h after the initial MRI, and the patients were divided into two groups based on the results. Demographic and clinical data, including initial National Institutes of Health Stroke Scale scores, ABCD and ABCD(2) scores, and other MRI findings were evaluated. The data were analyzed using Spearman's rank tests and unpaired t tests. Ten patients (32.3 %) showed diffusion lesions on the second DWI examination. Both risk scores were higher in these patients compared with patients with negative results on follow-up DWI (P < 0.05, unpaired t test) and correlated with the length of the TIA (R s = 0.017, P < 0.05; R s = 0.003, P < 0.01; Spearman's rank test). Our results suggest that TIA patients with high-risk scores might be underestimated if the first MRI was performed within 24 h of symptom onset.
(Keyword)
Aged / Diffusion Magnetic Resonance Imaging / Female / Humans / Incidence / Ischemic Attack, Transient / Japan / Male / Reproducibility of Results / Risk Assessment / Sensitivity and Specificity / Time Factors
Yukio Yamamura, Ryoma Morigaki, Jiro Kasahara, Hironori Yokoyama, Akie Tanabe, Shinya Ohkita, Hidetaka Koizumi, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice, Frontiers in Cellular Neuroscience, Vol.7, No.12, 1-10, 2013.
(Summary)
Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum.
Koji Fujita, W Sakai, Masafumi Harada, Mika Sakaki, Hideo Mure, Shinji Nagahiro, Yuishin Izumi and Ryuji Kaji : Basal ganglia hyperintensity on T1-weighted imaging of a patient with central nervous system metastasis producing carcinoembryonic antigens, Internal Medicine, Vol.52, No.3, 381-383, 2013.
(Summary)
We herein report unusual basal ganglia hyperintense lesions on noncontrast T1-weighted magnetic resonance imaging in a patient with central nervous system metastasis from lung adenocarcinoma that was treated with gefitinib. T2*-weighted magnetic resonance imaging showed no hypointense lesions, thereby excluding the possibility of calcification or haemorrhage. A stereotactic brain biopsy of the left basal ganglia lesions revealed atypical cells, some of which formed a glandular lumen with a micropapillary pattern. These cells were immunopositive for markers of lung adenocarcinoma, thereby confirming the diagnosis of metastasis. We speculate that proteins, including carcinoembryonic antigens from the adenocarcinoma cells in the basal ganglia, may have contributed to the hyperintensity observed on noncontrast T1-weighted magnetic resonance imaging.
Junichiro Satomi, Yoshiteru Tada and Shinji Nagahiro : A Case of Cervical Extradural Arteriovenous Fistula presenting with Radiculopathy, Japanese Journal of Neurosurgery, Vol.22, No.1, 69-71, 2013.
Junichiro Satomi and Shinji Nagahiro : Significance and future perspective of stroke care unit in Tokushima university hospital, Shikoku Acta Medica, Vol.68, No.5,6, 165-168, 2012.
(Summary)
Cerebral Stroke such as cerebral infarction, intracerebral hemorrhage and subarachnoid hemorrhage is a leading cause of being a bed-ridden state, thus measures against cerebral stroke are still ongoing issue. The university hospital which provides optimal treatment using advanced techniques must struggle to develop emergency medicine including acute cerebral stroke management. Stroke care unit was founded in 1999 in Tokushima university hospital and has contributed to educate medical students, to train junior residents and to promote clinical research with multidisciplinary approach. Furthermore, we adopted i-Stroke system which allows us to browse clinical data including radiological images and to discuss each other by smartphone. This system provided urgent management decision in acute stroke and contribute to improvement not only patients' outcome but physicians' quality of life. The university hospital must also construct a supporting system on medically underpopulated region in future.
(Keyword)
stroke care unit / university hospital / smartphone
Teruyoshi Kageji, Hirofumi Oka, Junichiro Satomi, 岡﨑 敏之, Yasuhisa Kanematsu, Yoshifumi Mizobuchi and Shinji Nagahiro : The present conditions of the emergency care of South Tokushima and new action : From a neurosurgical viewpoint, Shikoku Acta Medica, Vol.68, No.5,6, 177-182, 2012.
(Summary)
A regular neurosurgeon was absent in the southern part II health demographic division of medical services where Kaifu-gun of South Tokushima was located after 2008 and was the present conditions that stroke treatment could not perform enough in comparison with prefecture central part. Furthermore, medical care collapse progressed with the obstetrics and gynecology department and pediatrics closedown at one sweep from the same period and, at the prefectural Kaifu Hospital which was this local nucleus hospital, became hard to maintain the emergency care, and increase of closedown of the emergency outpatient department on Saturday and the emergency transportation to the prefecture central part became remarkable, and it was with a big social problem for Tokushima. A medical difference might occur about stroke medical care in central part and the southern part in Tokushima. We performed the epidemiology survey by stroke patient in the southern II demographic division of medical services (popular name ``Kaifu project'') as a President of University of Tokushima discretion project for this fact-finding individually in the University of Tokushima neurosurgery classroom. In addition, I worked on the enlightenment for inhabitants in Kaifu-gun. ``Local neurosurgical medical treatment part'' was established as a college course financially maintained by private donations of Tokushima University Hospital from November 1，2011． Kaifu Hospital neurosurgery medical treatment was enabled daylong, and emergency correspondence came to be in this way possible. The Kaifu Hospital devises the maintenance policy about Tokushima, local inhabitants, a medical association, a local government and the figure which there should be of ``the new Kaifu Hospital'' for a tsunami now in the plan of the full-scale reconstruction move to the hill in 2015．
羽星 辰哉, Kenji Yagi, Yoshiteru Tada, Nobuhisa Matsushita, Yasuhisa Kanematsu, Mika Bando, Yuka Ueda, Hirotsugu Yamada, Junichiro Satomi, Kyoko Nishi, Masataka Sata and Shinji Nagahiro : A clinical study on severe neurogenic stress cardiomyopathy after subarachnoid hemorrhage, Shikoku Acta Medica, Vol.68, No.5, 6, 233-238, 2012.
Tomoya Kinouchi, Keiko T. Kitazato, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Nobuhisa Matsushita, Manabu Sumiyoshi, Junichiro Satomi, Teruyoshi Kageji and Shinji Nagahiro : Activation of signal transducer and activator of transcription-3 by a peroxisome proliferator-activated receptor gamma agonist contributes to neuroprotection in the peri-infarct region after ischemia in oophorectomized rats, Stroke, Vol.43, No.2, 478-483, 2012.
(Summary)
The role of the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) after cerebral ischemia by the peroxisome proliferator-activated receptor (PPAR) agonist pioglitazone (PGZ) remains controversial. Whether the increase in p-STAT3 by estrogen is mediated by the estrogen receptor is also obscure. We examined the role of p-STAT3, PPAR, and estrogen receptor against ischemic brain damage after PGZ treatment. Female Wistar rats subjected or not subjected to bilateral oophorectomy were injected with 1.0 or 2.5 mg/kg PGZ 2 days, 1 day, and 1 hour before 90-minute middle cerebral artery occlusion-reperfusion and compared with vehicle-control rats. The cortical infarct size was larger in ovariectomized than in nonovarietomized rats; it was reduced by PGZ treatment. Inversely with the reduction of the infarct size, PPAR, and p-STAT3 but not estrogen receptor in the peri-infarct area were increased in PGZ-treated compared with vehicle-control rats. The increase in PPAR and p-STAT3 was associated with the transactivation of antiapoptotic and survival genes and the reduction of caspase-3 in this area. Inhibitors of PPAR or STAT3 abolished the PGZ-induced neuroprotection and the increase in p-STAT3. More importantly, p-STAT3 increased by PGZ was bound to PPAR and the complex translocated to the nucleus to dock to the response element through p-STAT3. Our findings suggest that the activation in the peri-infarct region of p-STAT3 and PPAR by PGZ is essential for neuroprotection after ischemia and that PGZ may be of benefit even in postmenopausal stroke patients.
Nobuhisa Matsushita, Keiko T. Kitazato, Yoshiteru Tada, Manabu Sumiyoshi, Kenji Shimada, Kenji Yagi, Yasuhisa Kanematsu, Junichiro Satomi and Shinji Nagahiro : Increase in body Na+-to-water ratio is associated with cerebral aneurysm formation in oophorectomized rats, Hypertension, Vol.60, No.5, 1309-1315, 2012.
(Summary)
The incidence of cerebral aneurysms is higher in women than in men, especially postmenopause. Although hypertension is thought to be associated with a high incidence of stroke, not all patients with unruptured cerebral aneurysms are hypertensive. The possibility of water-free Na(+) storage associated with hypertension has been raised. However, whether the increase in the body Na(+)/water ratio that characterizes water-free Na(+) accumulation is associated with the formation of cerebral aneurysms remains obscure. To examine this relationship, Sprague-Dawley female rats subjected to carotid artery ligation were divided into 3 groups: a high-salt diet group (HSD) without and another with bilateral oophorectomy (HSD/OVX) and a third group that underwent additional renal artery ligation (HSD/OVX/RL). Compared with rats receiving a normal diet (shams), water retention was increased in HSD rats but not in HSD/OVX rats. Interestingly, compared with HSD rats, the incidence of cerebral aneurysms and the body Na(+)/water ratio were significantly higher in HSD/OVX and HSD/OVX/RL rats, independent of hypertension. In their aneurysmal wall, ATP12, a subtype of Na(+)/K(+)-ATPase, was downregulated, whereas inflammatory-related molecules were upregulated. Treatment with low-dose olmesartan that did not affect the blood pressure in hypertensive HSD/OVX/RL rats reduced the rate of cerebral aneurysm formation, body Na(+) retention, and the Na(+)/water ratio and upregulated ATP12. These results suggest that the increase in the Na(+)/water ratio and a reduction in ATP12 may be associated with cerebral aneurysm formation. We provide the new insight that the management of water-free Na(+) is important to prevent their development.
Mika Bando, Hirotsugu Yamada, 西尾 進, 玉井 利奈, 平田 有紀奈, 弘田 大智, 中川 摩耶, 林 修司, 冨田 紀子, 發知 淳子, 小笠原 梢, 高島 啓, 山崎 宙, 坂東 左知子, Takayuki Ise, Toshiyuki Niki, Yuka Ueda, Koji Yamaguchi, Takashi Iwase, Yoshio Taketani, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata, Yasuhisa Kanematsu, Junichiro Satomi and Shinji Nagahiro : Effect of statin therapy on carotid artery plaque assessed by integrated backscatter color mapping : Development of imaging analytical software and its application on 3 cases, Shikoku Acta Medica, Vol.68, No.3-4, 147-152, 2012.
(Summary)
Background : The carotid plaque vulnerability is related to myocardial and cerebral infarction.We intended to develop an imaging system which enables to visualize tissue characteristics in thecarotid plaques based on ultrasound integrated backscatter(IB). And to test its clinical efficacy,effect of the statin therapy on the plaques was evaluated with our software. Methods and Results :Carotid ultrasound examination was performed and ultrasonographic RAW data of the plaqueswere obtained from8patients undergoing carotid artery endarterectomy. Tissue characteristicsin the plaques of resected examples were compared with preoperative ultrasonic images and thetissue IB values corresponding to the specimens were determined for developing our imaging system.Using this system, Color-coded maps of plaques in the three patients were constructed beforeand after lipid lowing therapy. We could demonstrate that lipid fraction in each plaque decreasedand fibrous or calcification fraction increased in the follow-up study. Conclusions : Changes inhistology of carotid plaques by statin could visualized with our imaging system. This techniquemay become a useful tool for the management of atherosclerosis.
(Keyword)
IBS (integrated backscatter) / carotid plaque / CEA (carotid endarterectomy)
Ryosuke Miyamoto, Satoshi Goto, Wataru Sako, Ai Miyashiro, Isabelle Kim, Fabienne Escande, Masafumi Harada, Ryoma Morigaki, Koutaro Asanuma, Yoshifumi Mizobuchi, Shinji Nagahiro, Yuishin Izumi and Ryuji Kaji : Generalized dystonia in a patient with a novel mutation in the GLUD1 gene, Movement Disorders, Vol.27, No.9, 1198-1199, 2012.
A Kondo, I Date, S Endo, K Fujii, Y Fujii, T Fujimitsu, M Hasegawa, T Hatayama, K Hongo, T Inoue, M Ishikawa, M Ito, T Kayama, E Kohmura, T Matsushima, S Munemoto, Shinji Nagahiro, K Ohno, T Okumura, H Ryu, T Shigeno, R Shirane, Y Tagusagawa, H Tanabe, K Yamada and I Yamakami : A proposal for standardized analysis of the results of microvascular decompression for trigeminal neuralgia and hemifacial spasm, Acta Neurochirurgica, Vol.154, No.5, 773-778, 2012.
(Summary)
The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner. Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair. The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59). The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.
Yoshifumi Mizobuchi, Junichiro Satomi, Teruyoshi Kageji, Shinji Nagahiro and Masaji Nishimura : Evaluating stroke treatment in the south Tokushima ? medical areas without stroke specialists, Shikoku Acta Medica, Vol.68, No.1,2, 35-40, 2012.
(Summary)
INTRODUCTION:For cranial nerve diseases, particularly stroke, early-stage treatment by stroke specialists cansignificantly alter patient prognosis. With respect to the treatment of acute cerebral infarction, t‐PAwas approved for health insurance coverage in Japan in November2005, and has greatly influencedmedical practice. However, the use of t‐PA necessitates an expertise in stroke treatment, and thedrug cannot be used in areas where stroke specialists are absent. Consequently, disparities maybe occurring in stroke treatment among different areas. We accordingly aimed to evaluate strokepatients in the south Tokushima Ⅱ medical areas(south Ⅱ medical areas)without stroke specialistsand those transferred to the stroke care unit in the Stroke Center of Tokushima UniversityHospital(Tokushima University Hospital SCU), and to clarify the presence or absence of disparitiesin area-based stroke treatment in Tokushima.METHODS:The subjects were103stroke patients in the south Tokushima Ⅱ medical areas without strokespecialists and 317 stroke patients in Tokushima University Hospital SCU, who were assessedbetween October1，2009and September30，2010.RESULTS:In the areas without stroke specialists, the prognosis of42% of the cerebral infarction patientswas related to the absence of stroke specialists, and to geographical disadvantages. In48% of thecerebral infarction patients in the areas without stroke specialists, the lapse time after the onset ofcerebral infarction exceeded3h at their initial examinations. However, this is considered likely tobe improved by the implementation of stroke awareness activities.DISCUSSION:Cerebral infarction, which is common in the elderly, is expected to increase in frequency andseverity in the future. Therefore, rigorous prevention, awareness activities to spread super-acutestroke treatment using t‐PA, and medical environmental improvement are necessary.
(Keyword)
t-PA / stroke care / cerebral infarction / south Tokushima ? medical areas
Toshiyuki Okazaki, Teruyoshi Kageji, Kazuyuki Kuwamura, Keiko T. Kitazato, Hideo Mure, Keijiro Hara, Ryoma Morigaki, Yoshifumi Mizobuchi, Kazuhito Matsuzaki and Shinji Nagahiro : Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma, Cancer Letters, Vol.323, No.2, 199-207, 2012.
(Summary)
Interferon-beta (IFN-) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN--induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.
Yoshimi Bando, Tetsuyuki Takahashi, Hisanori Uehara, Teruyoshi Kageji, Shinji Nagahiro and Keisuke Izumi : Autopsy case of amebic granulomatous meningoencephalitis caused by Balamuthia mandrillaris in Japan, Pathology International, Vol.62, No.6, 418-423, 2012.
(Summary)
Balamuthia mandrillaris is a free-living ameba that causes amebic encephalitis. Herein, we report an autopsy case of Balamuthia encephalitis proven with polymerase chain reaction (PCR) and immunohistochemistry from paraffin-embedded brain biopsy specimens. A 68-year-old Japanese male presented at a hospital with progressive right hemiparesis approximately 3 months before his death. An open-brain biopsy specimen showed diffuse meningitis with massive coagulative necrosis. The perivascular spaces contained numerous lymphocytes, histiocytes and giant cells, although the etiology was not determined. The patient deteriorated into coma and died from cerebral herniation. Autopsy revealed abundant trophozoites and cysts in the subarachnoid and Virchow-Robin's spaces. Electron-micrographs of the amebic cysts showed a characteristic triple-walled envelope. The amebas were identified as Balamuthia mandrillaris based on immunohistochemical analysis from the autopsy and biopsy specimens. Primer sets designed to amplify approximately 200 bp bands of mitochondrial 16S rRNA gene of Balamuthia by PCR produced positive results from the biopsy specimens but negative results from the autopsy specimens. In summary, PCR to amplify shorter segments of DNA may be of diagnostic value in detecting suspected cases of balamuthiasis in formalin-fixed, paraffin-embedded specimens. Increased awareness and timely diagnosis of Balamuthia encephalitis might lead to earlier initiation of therapy and improved outcome.
(Keyword)
Amebiasis / Balamuthia mandrillaris / Brain / Central Nervous System Protozoal Infections / Fatal Outcome / Humans / Japan / Magnetic Resonance Imaging / Male / Treatment Failure
Ryoma Morigaki, Junichiro Satomi, E Shikata and Shinji Nagahiro : Aneurysm of the lateral spinal artery: A case report, Clinical Neurology and Neurosurgery, Vol.114, 713-716, 2012.
S Okita, Ryoma Morigaki, H Koizumi, Ryuji Kaji, Shinji Nagahiro and Satoshi Goto : Cell type-specific localization of optineurin in the striatal neurons of mice: Implications for neuronal vulnerability in huntington's disease, Neuroscience, Vol.202, No.27, 363-370, 2012.
(Summary)
Striatal neuropathology of Huntington's disease (HD) involves primary and progressive degeneration of the medium-sized projection neurons, with relative sparing of the local circuit interneurons. The mechanism for such a patterned cell loss in the HD striatum continues to remain unclear. Optineurin (OPTN) is one of the proteins interacting with huntingtin and plays a protective role in several neurodegenerative disorders. To determine the cellular localization pattern of OPTN in the mouse striatum, we employed a highly sensitive immunohistochemistry with the tyramide signal amplification system. In this study, we show that OPTN appeared as a cytoplasmic protein within the subsets of the striatal neurons. Of particular interest was that OPTN was abundantly expressed in the interneurons, whereas low levels of OPTN were observed in the medium projection neurons. This cell type-specific distribution of OPTN in the striatum is strikingly complementary to the pattern of neuronal loss typically observed in the striatum of patients with HD. We suggest that OPTN abundance is an important cellular factor in considering the cell type-specific vulnerability of striatal neurons in HD.
(Keyword)
Animals / Blotting, Western / cell death / Corpus Striatum / Densitometry / Eye Proteins / Glutamic Acid / Huntington Disease / Image Processing, Computer-Assisted / immunohistochemistry / Interneurons / Male / Mice / Mice, Inbred C57BL / Mice, Transgenic / Mutation / Neurons / Serotonin Plasma Membrane Transport Proteins
Shinji Nagahiro, Yoshifumi Mizobuchi, 本藤 秀樹, 糟谷 英俊, 紙谷 武, 新原 勇三, 二村 雄次 and 戸松 泰介 : [Severe head injuries during Judo practice]., Neurological Surgery, Vol.39, No.12, 1139-1147, 2011.
(Summary)
The goal of this study is to elucidate the characteristic features of Judo head injuries and to propose safety measures and a reaction manual on how to prevent and to deal with such accidents in Japan. Thirty cases of severe head injuries suffered during Judo practice were enrolled in this study. They have made insurance claims for damage compensation and inquiries about Judo accidents attributed to the All Japan Judo Federation, from 2003 to 2010. The average age of the patients was 16.5 year old. The incidence of injury showed 2 peaks in different academic grade levels; one is in the first year of junior high-school (30.0%, n=9) and the other is in senior high school (26.7%, n=8). Around half of them were beginners. Four cases (13.3%) had past history of head trauma or headache and dizziness before a catastrophic accident, suggesting the presence of a second impact. Lucid interval was observed in 25 cases (83.3%). Most patients (93.3%) suffered acute subdural hematoma associated with avulsion of a cerebral bridging vein. Of patients who underwent emergency removal of the hematoma, 15 patients (50%) died and 7 patients (23.3%) entered a persistent vegetative state. Based on these findings, we propose an emergency manual with safety measures for effectively preventing and treating Judo head injuries in an appropriate manner. To reduce the disastrous head injuries in Judo, the safety measures and an optimal action manual should be reconsidered and widely spread and accepted by society.
(Keyword)
Adolescent / Adult / Aged / Child / Craniotomy / Fatal Outcome / Female / Head Injuries, Closed / Hematoma, Subdural, Acute / Humans / Japan / Male / Martial Arts / Middle Aged / Prognosis / Trauma Severity Indices / Young Adult
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● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22128268
Norio Nakajima, Shinji Nagahiro, Toshiaki Sano, Junichiro Satomi, Kenji Yagi, Yoshiteru Tada, Keiko T. Kitazato and Koichi Satoh : Krüppel-like zinc-finger transcription factor 5 (KLF5) is highly expressed in large and giant unruptured cerebral aneurysms., World Neurosurgery, Vol.78, No.1-2, 114-121, 2011.
(Summary)
Krüppel-like zinc-finger transcription factor 5 (KLF5), known as BTEB2 and IKLF, has several biological functions that involve cell proliferation, development, and apoptosis. In human cerebral aneurysms, macrophage infiltration is profoundly associated with growth and rupture, but the role of KLF5 remains unclear. We examined the significance of KLF5 expression in cerebral aneurysms. Unruptured (n=15) and ruptured (n=12) aneurysms obtained at surgery or autopsy were divided into 3 size groups: small (<10 mm); large (10 mm but <25 mm); and giant (25 mm). Control samples comprised 5 cerebral arteries obtained from surgery or autopsy subjects. The expression of KLF5-, -smooth muscle actin-, and KP-1 (macrophages) -positive cells were counted and compared between groups. Media of control arteries was negative for KLF5. In the luminal layers, KLF5 in unruptured small aneurysm was also negative; KLF5 expression was higher in unruptured large/giant aneurysms than other groups (P<0.05). KP-1 expression in unruptured large/giant aneurysms, ruptured small aneurysms, and ruptured large/giant aneurysms was higher than in unruptured small aneurysms (P<0.05). In the unruptured large/giant aneurysms, KP-1-positive cells were lower than KLF5-positive cells. On the other hand, irrespective of size, KLF5 positivity tended to be lower than KP-1 in the luminal and abluminal layers of all ruptured aneurysms. This represents the first documentation that KLF5 is highly expressed in large and giant unruptured aneurysms and that in ruptured aneurysmal wall KLF5 expression was scarce. These findings suggest that the KLF5 expression and macrophage infiltration play essential roles on aneurysmal growth or rupture.
斎藤 孝次 and Shinji Nagahiro : Special Interview 私の病院経営術ー地域に貢献し，地域と共に歩む医療ー, Practical Currently, Vol.21, No.9, 950-957, 2011.
175.
Ryoma Morigaki, Wataru Sako, Shinya Okita, Jiro Kasahara, Hironori Yokoyama, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Cyclin-dependent kinase 5 with phosphorylation of tyrosine 15 residue is enriched in striatal matrix compartment in adult mice, Neuroscience, Vol.189, 25-31, 2011.
(Summary)
Accumulating evidence suggests that the striosome-matrix systems have a tight link with motor and behavioral brain functions and their disorders. Cyclin-dependent kinase 5 (Cdk5) is a versatile protein kinase that plays a role in synaptic functions and cell survival in adult brain, and its kinase activity is stimulated by phosphorylation at tyrosine 15 residue (pY15). In this study, we used an immunohistochemical method to show differential localization of Cdk5-pY15 in the striatal compartments of adult mice, with a heightened density of Cdk5-pY15 labeling in the matrix relative to the striosomes. Our findings indicate that Cdk5-pY15 can be a new marker for the striatal matrix compartment, and suggest a possible involvement of Cdk5-mediated signaling in compartment-specific neurotransmission and disease pathology in the striatum.
Wataru Sako, Ryoma Morigaki, Ryuji Kaji, Ikuo Tooyama, Shinya Okita, Keiko Kitazato, Shinji Nagahiro, M Ann Graybiel and Satoshi Goto : Identification and localization of a neuron-specific isoform of TAF1 in rat brain: implications for neuropathology of DYT3 dystonia, Neuroscience, Vol.189, 100-107, 2011.
(Summary)
The neuron-specific isoform of the TAF1 gene (N-TAF1) is thought to be involved in the pathogenesis of DYT3 dystonia, which leads to progressive neurodegeneration in the striatum. To determine the expression pattern of N-TAF1 transcripts, we developed a specific monoclonal antibody against the N-TAF1 protein. Here we show that in the rat brain, N-TAF1 protein appears as a nuclear protein within subsets of neurons in multiple brain regions. Of particular interest is that in the striatum, the nuclei possessing N-TAF1 protein are largely within medium spiny neurons, and they are distributed preferentially, though not exclusively, in the striosome compartment. The compartmental preference and cell type-selective distribution of N-TAF1 protein in the striatum are strikingly similar to the patterns of neuronal loss in the striatum of DYT3 patients. Our findings suggest that the distribution of N-TAF1 protein could represent a key molecular characteristic contributing to the pattern of striatal degeneration in DYT3 dystonia.
(Keyword)
Amino Acid Sequence / Animals / Base Sequence / brain / Corpus Striatum / Dystonia / Histone Acetyltransferases / Molecular Sequence Data / Nuclear Proteins / Protein Isoforms / Rats / Rats, Sprague-Dawley / TATA-Binding Protein Associated Factors / Transcription Factor TFIID
Michiharu Kashihara, Shigetaka Nakao, Jun Kawasaki, Shinjiro Takata, Shinji Nagahiro, Ryuji Kaji and Natsuo Yasui : Long-term outcome of severe stroke patients: Is the ADL status at discharge from a stroke center indicative of the long-term outcome?, The Journal of Medical Investigation : JMI, Vol.58, No.3-4, 227-234, 2011.
(Summary)
The objective of this study was to examine the possibility of predicting the long-term outcome of severe stroke patients from the ADL status at discharge. The design is a retrospective observational study in the stroke center at Tokushima University Hospital. Severe stroke patients at discharge with Barthel Index (BI) scores 40 (N=51) were divided into two subgroups retrospectively, improved and unimproved. The Functional Independence Measure (FIM) and BI were analyzed at discharge, 3 and 6 months after onset. Correlation analysis between BI and FIM showed good correlation, especially between BI and motor FIM (mFIM). In conclusion, the ADL status at discharge from a stroke center is not definitely indicative of the long-term outcome, although good recovery of severe stroke cases was observed in males and younger patients, and in patients with motor FIM score>25. This result shows that the first 3 months after the attack should be regarded as an important time window for intensive rehabilitation.
(Keyword)
Activities of Daily Living / Aged / Female / Humans / Male / Middle Aged / Patient Discharge / Retrospective Studies / Stroke
Shigetaka Nakao, Kouji Komatsu, Waka Sakai, Michiharu Kashihara, Yuki Masuda, Koji Nishikawa, Tetsuya Okahisa, Shin Kondo, Toshifumi Osawa, Ryuji Kaji, Satoshi Goto, Shinji Nagahiro, Shinjiro Takata and Natsuo Yasui : Gait and posture assessments of a patient treated with deep brain stimulation in dystonia using three-dimensional motion analysis systems., The Journal of Medical Investigation : JMI, Vol.58, No.3-4, 264-272, 2011.
(Summary)
Kinesiologic analysis of gait disorders, postural instabilities and abnormal movements is quite difficult to assess objectively by clinical observation, such as by specific scale and video recordings. In this study, we reported one of the aspects of the usefulness of three-dimensional motion analysis (Vicon Systems, Oxford, United Kingdom), which can measure inclusive data of movement disorders and substitute for conventional assessments. A 49-year-old man who had various dystonic symptoms, mainly on his left side of the body, responded well to deep brain stimulation (DBS). The examination quantified how the involuntary movements or other symptoms with dystonia changed before and after treatments.
(Keyword)
Deep Brain Stimulation / Dystonia / Gait / Humans / Male / Middle Aged / Motion / Posture
Yoshiteru Tada, Keiko T. Kitazato, Kenji Yagi, Kenji Shimada, Nobuhisa Matsushita, Tomoya Kinouchi, Yasuhisa Kanematsu, Junichiro Satomi, Teruyoshi Kageji and Shinji Nagahiro : Statins Promote the Growth of Experimentally Induced Cerebral Aneurysms in Estrogen-Deficient Rats, Stroke, Vol.42, No.8, 2286-2293, 2011.
(Summary)
The pathogenesis of cerebral aneurysms is linked to inflammation, degradation of the extracellular matrix, and vascular wall apoptosis. Statins exert pleiotropic effects on the vasculature, independent of their cholesterol-lowering properties. To explore the detailed pathogenesis of cerebral aneurysms, we examined their progression in a rat model and studied whether statins prevent their initiation and growth. Cerebral aneurysms were induced in female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The development of aneurysm was assessed morphologically on corrosion casts. The effects of pravastatin (5, 25, or 50 mg/kg per day) and of simvastatin (5 mg/kg per day) on their aneurysms were studied. Human brain endothelial cells were also used to determine the effects of pravastatin. Pravastatin (5 mg/kg per day) reduced endothelial damage and inhibited aneurysm formation; there was an association with increased endothelial nitric oxide synthase (eNOS) levels and a decrease in human brain endothelial cell adhesion molecules. Unexpectedly, 25 mg/kg per day and 50 mg/kg per day pravastatin and 5 mg/kg per day simvastatin promoted aneurysmal growth, and high-dose pravastatin induced aneurysmal rupture. The deleterious effects exerted by these statins were associated with an increase in apoptotic caspase-3 levels and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, suggesting that statins exert bidirectional effects. Our results provide the first evidence that cerebral aneurysm growth is partly associated with apoptosis and issue a warning that statins exert bidirectional effects on cerebral aneurysms. Additional intensive research is necessary to understand better their mechanisms and to identify patients in whom the administration of statins may elicit deleterious effects.
Shinji Nagahiro and Keiko T. Kitazato : 脳梗塞急性期血管破綻の分子メカニズム, 分子脳血管病, Vol.10, No.3, 278-284, 2011.
182.
Teruyoshi Kageji, Yoshifumi Mizobuchi, Shinji Nagahiro, Y Nakagawa and H Kumada : Clinical results of boron neutron capture therapy (BNCT) for glioblastoma, Applied Radiation and Isotopes, Vol.69, No.12, 1823-1825, 2011.
(Summary)
The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.
Teruyoshi Kageji, Yoshifumi Mizobuchi, Shinji Nagahiro, Y Nakagawa and H Kumada : Boron neutron capture therapy combined with fractionated photon irradiation for glioblastoma: A recursive partitioning analysis of BNCT patients, Applied Radiation and Isotopes, Vol.69, No.12, 1790-1792, 2011.
(Summary)
Eight patients to received Boron Neuron Capture Therapy (BNCT) were selected from 33 newly diagnosed glioblastoma patients (NCT(+) group). Serial 42 glioblastoma patients (NCT(-) group) were treated without BNCT. The median OS of the NCT(+) group and NCT (-) group were 24.4 months and 14.9 months. In the high risk patients (RPA class V), the median OS of the NCT(+) group tended to be better than that of NCT(-) group. 50% of BNCT patients were RPA class V.
Kenji Shimada, Keiko T. Kitazato, Tomoya Kinouchi, Kenji Yagi, Yoshiteru Tada, Junichiro Satomi, Teruyoshi Kageji and Shinji Nagahiro : Activation of estrogen receptor- and of angiotensin-converting enzyme 2 suppresses ischemic brain damage in oophorectomized rats., Hypertension, Vol.57, No.6, 1161-1166, 2011.
(Summary)
Like the angiotensin II type 1 receptor blocker, endogenous estrogen (17-estradiol) is neuroprotective against cerebral ischemia; its effects are thought to be mediated by estrogen receptors (ERs). To verify the role of ERs and the brain renin-angiotensin system in estrogen-deficient rats with ischemia induced by middle cerebral artery occlusion, we compared rats subjected to oophorectomy (OVX(+)) with sham-oophorectomized rats (OVX(-)) and OVX(+) rats treated with 0.3 or 3.0 mg/kg of olmesartan for 2 weeks before middle cerebral artery occlusion. Independent of the blood pressure, the cortical infarct volume was larger in OVX(+) than in OVX(-) rats. It was smaller in olmesartan-pretreated OVX(+) rats. The expression of ER in the peri-infarct region was correlated with the reduction of cortical infarct but not that of ER or G protein-coupled estrogen receptor. Olmesartan prevented ER downregulation in the cortical peri-infarct area, without affecting ER or G protein-coupled estrogen receptor. Olmesartan also increased mRNA expression of angiotensin-converting enzyme 2, Bcl-2, and Bcl-xL and reduced angiotensin II and cleaved caspase 3. These effects were augmented by olmesartan and abolished by the ER inhibitor. In OVX(+) rats treated with the ER agonist alone, the infarct size was decreased, and the neuroprotective genes were upregulated. These findings suggest that the transactivation of neuroprotective genes and the reduction in brain angiotensin II are ER dependent and that this may augment neuroprotection together with an angiotensin II type 1 receptor blockade by olmesartan. We present the new insight that the activation of ER independent of estrogen contributes at least partly to limiting cerebral ischemic damage.
Yuishin Izumi, 中村 和己 and Shinji Nagahiro : Diagnostic criteria of the administrative higher brain dysfunction, Shikoku Acta Medica, Vol.67, 29-34, 2011.
(Summary)
Diagnostic criteria of the administrative higher brain dysfunction are defined. Young people between the period of entering school and starting work occasionally suffer from brain damage. Although the patient may seem to recover, memory and attention disturbances may continue. As a result, higher brain dysfunction may interfere with return to school, and reinstatement is difficult.Patients diagnosed with higher brain dysfunction by these diagnostic criteria can continue rehabilitation and achieve functional restoration. In the Tokushima University Hospital, many patients with cerebrovascular disease, brain tumor, or traffic injury(in that order)consulted about higher brain dysfunction.
Teruyoshi Kageji, Yoshifumi Mizobuchi, Shinji Nagahiro, Y Nakagawa and H Kumada : Long-survivors of glioblastoma treated with boron neutron capture therapy (BNCT), Applied Radiation and Isotopes, Vol.69, No.12, 1800-1802, 2011.
(Summary)
The purpose of this study was to compare the radiation dose between long-survivors and non-long-survivors in patients with glioblatoma (GBM) treated with boron neutron capture therapy (BNCT). Among 23 GBM patients treated with BNCT, there were five patients who survived more than three years after diagnosis. The physical and weighted dose of the minimum gross tumor volume (GTV) of long-survivors was much higher than that of non-long survivors with significant statistical differences.
Shinji Nagahiro : 改正臓器移植法と脳神経外科医, The Journal of the Japan Medical Association, Vol.139, No.12, 2531-2535, 2011.
189.
横田 裕行, Shinji Nagahiro, 有賀 徹 and 松井 陽 : 福嶌教偉 救急医療・脳神経外科施設からみた脳死下臓器提供の現況と課題, The Journal of the Japan Medical Association, Vol.139, No.12, 2497-2510, 2011.
190.
Wataru Sako, Ryoma Morigaki, Yoshifumi Mizobuchi, Takashi Tsuzuki, Hiroyuki Ima, Y Ushio, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Bilateral pallidal deep brain stimulation in primary Meige syndrome, Parkinsonism & Related Disorders, Vol.17, No.2, 123-125, 2011.
(Summary)
Primary Meige syndrome is an idiopathic movement disorder that manifests as craniofacial and often cervical dystonias. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as a powerful surgical option in the treatment of primary generalized or segmental dystonia. However, the experience with GPi-DBS in Meige syndrome is limited. We followed 5 patients with disabling Meige syndrome treated by bilateral GPi-DBS for 49 ± 43.7 (mean ± SD) months. All patients were assessed before surgery and at the last follow-up after surgery using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) which includes both the movement and disability scales. Bilateral GPi-DBS produced a sustained and long-lasting improvement in dystonia symptoms associated with Meige syndrome. At the last follow-up, the mean scores of BFMDRS movement and disability scales improved significantly by 84 ± 6.8% (range, 75-94%) and 89 ± 8.1% (range, 80-100%), respectively. Bilateral pallidal stimulation is a beneficial therapeutic option for long-term relief of the disabling dystonia symptoms in Meige syndrome.
Mami Hanaoka, Nobuhisa Matsushita, Koichi Satoh and Shinji Nagahiro : Dural arteriovenous fistulae after cerebral infarction: report of two cases, Neurosurgery, Vol.68, No.2, ES75-ES80, 2011.
(Summary)
We first report 2 patients in whom dural arteriovenous fistulae (dAVFs) developed after cerebral infarction. One patient was a 49-year-old man who had a right embolic stroke 6 months after his first ischemic attack. Angiograms showed a de novo left transverse sigmoid sinus dAVF. One year later, shunt flow through the dAVF was increased. The second patient was a 45-year-old woman who presented with right cerebral infarction and moyamoya disease. Three weeks later, she underwent right superficial temporal artery-middle cerebral artery bypass. Ten months after the operation, angiograms showed the development of dAVFs in the left transverse sigmoid sinus and progressive moyamoya disease. We document the first patients with cerebral infarction and progressive moyamoya disease in whom a de novo dAVF developed. Moyamoya disease and dAVF are associated with an increase in dural angiogenic factors, and ischemia induces their increase. This may be the mechanism by which vaso-occlusive ischemia contributes to the formation of de novo dAVFs.
(Keyword)
Central Nervous System Vascular Malformations / Cerebral Infarction / Embolization, Therapeutic / Female / Humans / Magnetic Resonance Angiography / Male / Middle Aged / Moyamoya Disease
Wataru Sako, Ryoma Morigaki, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Olfactory type G-protein alpha subunit in striosome-matrix dopamine systems in adult mice, Neuroscience, Vol.170, No.2, 497-502, 2010.
(Summary)
There is a growing body of evidence that striosome-matrix dopamine systems are tightly linked with motor and behavioral brain functions and disorders. In this study, we used an immunohistochemical method to show differential expression of the olfactory type G-protein alpha subunit (Galphaolf) that involves in the coupling of dopamine D1 receptor with adenylyl cyclase in the striatal compartments of adult mice, and observed heightened density of Galphaolf labeling in the striosomes relative to the matrix compartment. Our findings suggest that Galphaolf could be one of the key molecules for controlling differential responses of the striosome and matrix compartments to dopamine D1 receptor signaling in the striatum of adult mice.
(Keyword)
Animals / Apomorphine / Corpus Striatum / Dopamine / Dopamine and cAMP-Regulated Phosphoprotein 32 / GTP-Binding Protein alpha Subunits / Mice / Neurons / Receptors, Dopamine D1 / Receptors, Opioid, mu / Signal Transduction / Tyrosine 3-Monooxygenase
Yoshiteru Tada, Kenji Yagi, Keiko T. Kitazato, Tetsuya Tamura, Tomoya Kinouchi, Kenji Shimada, Nobuhisa Matsushita, Norio Nakajima, Junichiro Satomi, Teruyoshi Kageji and Shinji Nagahiro : Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats., Journal of Hypertension, Vol.28, No.9, 1883-1891, 2010.
(Summary)
OBJECTIVE: The formation of cerebral aneurysms is associated with endothelial damage and macrophage migration. Hypothesizing that the opening of tight junctions due to the disappearance of the tight junction proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia allows macrophage migration, leading to cerebral aneurysm formation, we investigated the role of tight junction proteins. METHODS: The vascular wall of female rats subjected to hypertension, oophorectomy (OVX), and hemodynamic stress to induce cerebral aneurysms was evaluated morphologically, immunohistochemically, and by quantitative RT-PCR. We also assessed the regulation of tight junction proteins in human brain endothelial cells (HBECs). RESULTS: In the very early stage before aneurysm formation, the expression of occludin and ZO-1 was reduced in injured endothelial cell junctions exhibiting gaps. In the course of aneurysmal progression their reduction progressed and was correlated with macrophage migration. In hypertension along with OVX rats we observed an increase in angiotensin II and the degradation molecules matrix metalloproteinase-9 (MMP-9), nicotinamide-adenine dinucleotide phosphate oxidases and monocyte chemoattractant protein-1. The mineralocorticoid receptor blocker eplerenone increased occludin and ZO-1 expression; this was associated with a reduction in angiotensin II and the degradation molecules and resulted in the inhibition of macrophage exudation and aneurysm formation. In HBECs, occludin and ZO-1 downregulation by angiotensin II and estrogen deficiency was reversed by eplerenone, the MMP inhibitor SB3CT, and apocynin. Our results suggest that macrophage migration is associated with the reduction in tight junction proteins induced by the degradation molecules. CONCLUSION: In rats, the destruction of tight junctions may facilitate macrophage migration and cerebral-aneurysm formation.
Masaaki Uno, 戸井 宏行, Shunji Matsubara, 藤原 敏孝, 横須賀 公彦, Kazuhito Matsuzaki, 平野 一宏, 鈴木 康夫, Tomoya Kinouchi, 安井 信之 and Shinji Nagahiro : Microsurgical Management of Incomplete Coiled and Recurrent Aneurysms, Japanese Journal of Neurosurgery, Vol.19, No.8, 616-622, 2010.
(Summary)
We determined microsurgical techniques for treating previously coiled aneurysms and report the outcomes. Twelve symptomatic patients with incomplete or recurrent aneurysms were managed microsurgically. The necks of five incomplete coiled aneurysms were clipped (mean time to microsurgery, 35.5 days), and one was treated with bypass surgery. One of the patients who underwent neck clipping had bleeding during dissection of the aneurysm. Six patients who had recurrent aneurysms underwent microsurgery at a mean of 778 days after initial complete embolization. Two fully recovered from transient ischemic symptoms that occurred after microsurgery and the coil became extruded in one other patient. The necks of the aneurysms were clipped in five of these patients and the aneurysm was wrapped in one. Direct clipping is the preferred microsurgical treatment for coiled aneurysms. The necks of such aneurysms should be carefully clipped according to the timing of the surgery and the status of the aneurysm.
佐藤 雅美, 秩代 三宅, Masaaki Uno, Akishige Ikegame, 吉田 慎也, 千尋 井上, Kazuko Shono, 康孝 永峰, Toshio Doi and Shinji Nagahiro : Change of Platelet Aggregation During the Cessation of Antiplatelet Therapy in Patients with Cerebrovascular Reconstruction Surgery, Surgery for Cerebral Stroke, Vol.38, No.4, 261-265, 2010.
(Keyword)
antiplatelet agents / platelet aggregability / the maximum platelet aggregability rate / cerebrovascular reconstruction surgery
J Nakagawara, K Minematsu, Y Okada, N Tanahashi, Shinji Nagahiro, E Mori, Y Shinohara and T Yamaguchi : Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroked in routine clinical practice (The Japan post-marketing alteplase registration study (J-MARS), Stroke, Vol.41, No.9, 1984-1989, 2010.
(Summary)
In Japan, alteplase at 0.6 mg/kg was approved in October 2005 for use within 3 hours of stroke onset by the Ministry of Health, Labor and Welfare (MHLW). The aim of the Japan post-Marketing Alteplase Registration Study (J-MARS), which was requested by MHLW at the time of approval, was to assess the safety and efficacy of 0.6 mg/kg alteplase in routine clinical practice for the Japanese. A total of 7492 patients from 942 centers were enrolled in the J-MARS, an open-label, nonrandomized, observational study, from October 2005 to October 2007. Primary outcome measures were symptomatic intracranial hemorrhage (a deterioration in NIHSS score >or=4 from baseline) and favorable outcome (modified Rankin Scale score, 0-1) at 3 months after stroke onset. The proportion of patients with symptomatic intracranial hemorrhage in 7492 patients (safety analysis) was 3.5% (95% confidence interval [CI], 3.1%-3.9%) within 36 hours and 4.4% (95% CI, 3.9%-4.9%) at 3 months. The overall mortality rate was 13.1% (95% CI, 12.4%-13.9%) and the proportion of patients with fatal symptomatic intracranial hemorrhage was 0.9% (95% CI, 0.7%-1.2%). The outcomes at 3 months were available for 4944 patients and the proportion of favorable outcome (efficacy analysis) was 33.1% (95% CI, 31.8%-34.4%). The subgroup analysis in patients between 18 and 80 years with a baseline NIHSS score <25 demonstrated that favorable outcome at 3 months was 39.0% (95% CI, 37.4%-40.6%). These data suggest that 0.6 mg/kg intravenous alteplase within 3 hours of stroke onset could be safe and effective in routine clinical practice for the Japanese.
Shinji Nagahiro : [Revised act on organ transplantation from neurosurgeon's viewpoint]., Brain and Nerve = Shinkei kenkyū no shinpo, Vol.62, No.6, 575-581, 2010.
(Summary)
The revised act on organ transplantation was passed in July 2009; it will be implemented in July 2010. This law allows organ donation from a brain-dead person with or without an Organ Donation Decision Card, if the family members permit this donation and the brain-dead person had not decided against it when conscious. In Japan, the legal definition of human death has not changed after the revision of the act on organ transplantation; therefore, brain death is considered human death for the purpose of organ transplantation. Certain minor revisions are required in the medical and legal criteria for diagnosis of brain death, especially for children under 6 years. Ancillary tests, including radioisotope measurement of cerebral blood flow and auditory brainstem evoked potentials, should be considered for younger children or in cases where comprehensive neurological examination was not possible because of injuries to the face, eyes, or ears. An increase in the number of organ donations from brain-dead persons because of the revised act will greatly increase the responsibility of and burden on hospitals and neurosurgeons that treat many emergency cases of severe brain injury and stroke. Adequate socioeconomic and systemic medical support should be provided to hospitals where organ donation is carried out.
(Keyword)
Brain Death / Child / Humans / Japan / Neurosurgery / Organ Transplantation / Physicians / Tissue and Organ Procurement
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● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20548116
Masafumi Harada, Naomi Morita, Masaaki Uno, Junichiro Satomi, Yuishin Izumi, Koutaro Asanuma, Hiromu Nishitani, Ryuji Kaji and Shinji Nagahiro : Incidence and clinical correlation of intracranial hemorrhages observed by 3-tesla gradient echo T2*-weighted images following intravenous thrombolysis with recombinant tissue plasminogen activator, Cerebrovascular Diseases, Vol.29, No.6, 571-575, 2010.
(Summary)
The purpose of this study was to determine the incidence and clinical correlation of intracranial hemorrhages (ICHs) detected by 3-tesla gradient echo T(2)*-weighted images after intravenous recombinant tissue plasminogen activator (rt-PA) administration. We included 43 consecutive patients with anterior-circulation ischemia who underwent MRI studies before and after thrombolysis. Each hemorrhage was classified as a hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study definition. The clinical outcome was defined as an improvement (> or =4-point reduction) or deterioration (> or =4-point increase) based on a comparison between the initial and the 30-day NIHSS scores. The incidence of ICHs was 58%, and the HI rate was 52%; both were higher than the rates reported in the literature. Most of the patients with HI improved clinically, and these patients had second MRAs that showed recanalization. None of the patients with PH demonstrated improvement. Three-tesla MRI may reveal a higher frequency of HI type hemorrhages than lower-field MRIs, and HI may be a predictor of good recovery by reflecting the presence of recanalization. The rate of PH in our study was low compared to other studies, probably due to the lower dosage of rt-PA.
Toshiyuki Okazaki, Toru Nishi, Shigeo Yamashiro, Kazunari Koga, Shinji Nagahiro and Shodo Fujioka : De novo formation and rupture of an intracranial aneurysm 10 months after normal findings on conventional magnetic resonance angiography in a patient with no history of intracranial lesions -case report-, Neurologia Medico-Chirurgica, Vol.50, No.4, 309-312, 2010.
(Summary)
A 40-year-old male smoker presented with a ruptured saccular aneurysm that formed de novo 10 months after normal magnetic resonance (MR) angiography findings. Computed tomography of the head at the second admission showed subarachnoid hemorrhage in the interhemispheric fissure and anterior basal cistern. MR and conventional cerebral angiography revealed an aneurysm arising from the anterior communicating artery (AcomA). MR angiography performed 10 months earlier, when he experienced transient loss of consciousness, revealed no anomalies at the AcomA. Intraoperatively, the de novo aneurysm was found to be a typical saccular aneurysm with a fragile wall.
(Keyword)
Adult / Aneurysm, Ruptured / Humans / Intracranial Aneurysm / Magnetic Resonance Angiography / Male / Risk Factors / Rupture, Spontaneous / Subarachnoid Hemorrhage / Time Factors / Treatment Outcome
Hideo Mure, Kazuhito Matsuzaki, KT Kitazato, Yoshifumi Mizobuchi, Kazuyuki Kuwayama, Teruyoshi Kageji and Shinji Nagahiro : Akt2 and Akt3 play a pivotal role in malignant gliomas, Neuro-Oncology, Vol.12, No.3, 221-232, 2010.
(Summary)
Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well understood. Therefore, we examined the protein and mRNA expression patterns of Akt isoforms in tissues from human astrocytomas, glioblastomas, and non-neoplastic regions. We also explored the biological role of each Akt isoform in malignant glioma cells using RNA interference-mediated knock-down and the over-expression of plasmid DNA of each isoform. The expression of Akt1 protein and mRNA was similar in glioma and normal control tissues. Although the protein and mRNA level of Akt2 increased with the pathological grade of malignancy, the expression of Akt3 mRNA and protein decreased as the malignancy grade increased. In U87MG, T98G, and TGB cells, the down-regulation of Akt2 or Akt3 by RNA interference reduced the expression of the phosphorylated form of Bad, resulting in the induction of caspase-dependent apoptosis. Akt1 knock-down did not affect cell growth or survival. We first demonstrate that the over-expression of Akt2 or Akt3 down-regulated the expression of the other protein and that endogenous Akt3 protein showed high kinase activity in U87MG cells. Our data suggest that Akt2 and Akt3 play an important role in the viability of human malignant glioma cells. Targeting Akt2 and Akt3 may hold promise for the treatment of patients with gliomas.
Kenji Yagi, Yoshiteru Tada, Keiko T. Kitazato, Tetsuya Tamura, Junichiro Satomi and Shinji Nagahiro : Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats., Neurosurgery, Vol.66, No.3, 551-9;discussion559, 2010.
(Summary)
OBJECTIVE: Phosphodiesterase-4 (PDE-4) is a cyclic adenosine monophosphate-specific enzyme involved in various inflammatory diseases. We studied its role in and the effect of ibudilast, which predominantly blocks PDE-4, on rat cerebral aneurysms. METHODS: Cerebral aneurysms were induced at the anterior cerebral artery-olfactory artery bifurcation of female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The effect of ibudilast (30 or 60 mg/kg/d for 3 months) on their cerebral aneurysms was studied by morphological and immunohistochemical assessment and quantitative real-time polymerase chain reaction assay. In our in vitro study, we grew endothelial cells stimulated by angiotensin II under estrogen-free conditions and examined the effect of ibudilast on PDE-4 activation and the cyclic adenosine monophosphate level. RESULTS: Morphological evaluation using vascular corrosion casts showed ibudilast significantly suppressed cerebral aneurysms in a dose-dependent manner. In rats with induced cerebral aneurysms, the gene and protein expression of PDE-4 was high, and endothelial leukocyte adhesion molecules (P-selectin, intracellular adhesion molecule 1, and vascular adhesion molecule 1), matrix metalloproteinase-9, and tumor necrosis alpha were expressed. Macrophage migration was also increased. Treatment with ibudilast down-regulated these molecules, suppressed macrophage migration into the aneurysm wall, and inhibited PDE-4 activation and the elevation of cyclic adenosine monophosphate in endothelial cells. CONCLUSION: These results suggest that blocking of PDE4 is associated with the reduction of inflammation-related molecules and macrophage migration, thereby reducing the progression of cerebral aneurysms. It may represent a new conservative therapy to treat patients with cerebral aneurysms.
Kazuhito Matsuzaki, Teruyoshi Kageji, Hiroyoshi Watanabe, Takanori Hirose and Shinji Nagahiro : Pilomyxoid astrocytoma of the cervical spinal cord successfully treated with chemotherapy - case report -, Neurologia Medico-Chirurgica, Vol.50, No.10, 939-942, 2010.
(Summary)
A 15-month-old girl presented with a spinal pilomyxoid astrocytoma manifesting as a 3-month history of dysphagia. Magnetic resonance imaging showed an intramedullary mass of the cervical spinal cord at C1-C6 with syringobulbia. She underwent partial removal of the tumor and received postoperative chemotherapy with cisplatin and etoposide. The tumor completely responded to the treatment and has not relapsed for 64 months. Pilomyxoid astrocytoma frequently occurs in the opticohypothalamic regions but is rare in the spine. The present case suggests that surgery followed by chemotherapy with cisplatin and etoposide may be an effective therapeutic option for pilomyxoid astrocytoma of the cervical spinal cord.
Yoshiteru Tada, Masaaki Uno, Shunji Matsubara, Atsuhiko Suzue, Kenji Shimada, Naomi Morita, Masafumi Harada and Shinji Nagahiro : Reversibility of ischemic findings on 3-T T2*-weighted imaging after emergency superficial temporal artery-middle cerebral artery anastomosis in patients with progressive ischemic stroke., Neurologia Medico-Chirurgica, Vol.50, No.11, 1006-1011, 2010.
(Summary)
Vascular ischemic signs, i.e. multiple hypointense vessels in the ischemic territory, were identified by gradient echo-type 3-T T(2)*-weighted magnetic resonance (MR) imaging in 3 patients with acute ischemia due to major vessel occlusion. Emergency superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis was performed in 2 patients with progressive stroke caused by bleeding-type moyamoya disease or severe MCA stenosis. Both patients were initially treated conservatively, but their neurological signs deteriorated. 3-T T(2)*-weighted MR imaging detected funicular low signals in both patients indicating enhancement of cortical vessels or medullary veins. The area of the vascular ischemic signs was almost the same or smaller than the hypoperfusion area on perfusion-weighted MR imaging or single-photon emission computed tomography. Postoperatively, the vascular ischemic signs disappeared in both patients, suggesting a relationship with severe ischemia due to high-risk misery perfusion. Their postoperative course was uneventful, and MR imaging revealed no new cerebral ischemic lesions or cerebral hyperperfusion. The patient without surgery developed cerebral infarction in the area of the vascular ischemic signs. Vascular ischemic signs detected by 3-T T(2)*-weighted MR imaging may represent a new predictor of high-risk misery perfusion, and may disappear after STA-MCA anastomosis performed in the subacute stage.
Yoshiteru Tada, Keiko T. Kitazato, Tetsuya Tamura, Kenji Yagi, Kenji Shimada, Tomoya Kinouchi, Junichiro Satomi, Shinji Nagahiro and Shinji Nagahiro : Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats., Hypertension, Vol.54, No.3, 552-557, 2009.
(Summary)
Activation of the renin-angiotensin (Ang)-aldosterone system is involved in the pathology of vascular diseases. Although the blockade of the mineralocorticoid receptor protects against vascular diseases, its role in cerebral aneurysms remains to be elucidated. We treated female rats subjected to renal hypertension, increased hemodynamic stress, and estrogen deficiency for 3 months with the mineralocorticoid receptor blocker eplerenone (30 or 100 mg/kg per day) or vehicle (vehicle control). Eplerenone reduced the incidence of cerebral aneurysms and saline intake without lowering of the blood pressure. In the aneurysmal wall, the production of Ang II and nitrotyrosine was increased. The mRNA levels of Ang-converting enzyme 1 and NADPH oxidase subunits NOX4, Rac1, monocyte chemoattractant protein 1, and matrix metalloproteinase 9 were increased. Eplerenone brought about a reduction in these molecules, suggesting that mineralocorticoid receptor blockade suppresses cerebral aneurysm formation by inhibiting oxidative stress, inflammatory factors, local renin-Ang system activation, and saline intake. Other female rats implanted with pellets of the mineralocorticoid receptor agonist deoxycorticosterone acetate manifested a high incidence of cerebral aneurysm formation and the upregulation of molecules related to oxidative stress, inflammatory factors, and the local renin-Ang system; their saline intake was increased. We demonstrate that mineralocorticoid receptor activation at least partly contributes to the pathogenesis of cerebral aneurysms.
Tetsuya Tamura, Mohammad A. Jamous, Keiko T. Kitazato, Kenji Yagi, Yoshiteru Tada, Masaaki Uno and Shinji Nagahiro : Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats, Journal of Hypertension, Vol.27, No.6, 1284-1292, 2009.
(Summary)
Epidemiological data indicate a high incidence of cerebral aneurysms in postmenopausal women. To elucidate the pathogenesis of cerebral aneurysms, we focused on the contribution of endothelial damage in rats. We induced estradiol deficiency by oophorectomy (OVX), hypertension, or both, and hemodynamic stress in 7-week-old female Sprague-Dawley rats. They were then given hormone-replacement therapy with 17beta-estradiol or an angiotensin II type 1 receptor blocker (ARB). The effects of estradiol, angiotensin II type 1 receptor blocker, or both on cultured endothelial cells were also examined. The number of anomalously shaped endothelial cells was higher in OVX than hypertensive rats (P < 0.05). Rats subjected to hypertension and OVX exhibited a marked increase in the incidence of saccular cerebral aneurysms. Estradiol or angiotensin II type 1 receptor blocker treatment reduced this incidence (P < 0.05). The endothelial nitric oxide synthase (eNOS) mRNA level in the intracranial artery of OVX and hypertensive and OVX rats was low (P < 0.05). Immunohistochemically, the expression of eNOS and estrogen receptor alpha (ERalpha) in the vascular wall of hypertensive and OVX rats was decreased; angiotensin II and the nicotinamide adenine dinucleotide phosphate oxidase subunits nicotinamide adenine dinucleotide phosphate oxidase 4 and p22phox were strongly expressed in cerebral aneurysms. In the absence of estradiol, eNOS was downregulated and nicotinamide adenine dinucleotide phosphate oxidase expression was increased in endothelial cells; angiotensin II augmented these phenomena. The regulation of eNOS was mediated by ERalpha. These results suggest that estrogen deficiency induces endothelial dysfunction and reactive oxygen species generation, triggering endothelial damage that leads to cerebral aneurysms and that hypertension is an additional risk factor. A therapy targeted at the endothelium and management of hypertension may help to prevent cerebral aneurysms.
Wataru Sako, Masanori Nishioka, Tomoyuki Maruo, Hideki Shimazu, Kazuhito Matsuzaki, Tetsuya Tamura, Hideo Mure, Yukitaka Ushio, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease, Movement Disorders, Vol.24, No.7, 1076-1079, 2009.
(Summary)
Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinson's disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% +/- 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms.
H Yamasaki, Shunji Matsubara, J Sasaki and Shinji Nagahiro : Retinal artery embolization during carotid angioplasty and carotid artery stenting -case report-, Neurologia Medico-Chirurgica, Vol.49, No.5, 213-216, 2009.
(Summary)
A 69-year-old man presented with a rare case of retinal artery embolization, which occurred as a complication of carotid angioplasty and carotid artery stenting performed for recurrent cerebral infarction. Magnetic resonance imaging and angiography showed right internal carotid artery stenosis with ulceration. Carotid angioplasty and carotid artery stenting were performed using the distal protection system with the PercuSurge GuardWire. However, just after dilation, the patient complained of ocular pain and blurred vision on the right, which was subsequently diagnosed as retinal artery embolization. Heparin was given for 15 hours after stenting, and aspirin and ticlopidine medication were continued. The patient received hyperbaric oxygen therapy for 1 week. The patient's blurred vision gradually improved, but visual field defect remained. Debris was probably flushed into the external carotid artery, and passed through an anastomosis into the ophthalmic artery, resulting in retinal artery embolization.
Kenji Yagi, Keiko T. Kitazato, Masaaki Uno, Yoshiteru Tada, Tomoya Kinouchi, Kenji Shimada and Shinji Nagahiro : Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasmininogen activator, Stroke, Vol.40, No.2, 626-631, 2009.
(Summary)
Intracerebral hemorrhage, induced by recombinant tissue plasminogen activator (rtPA) in ischemic stroke, is attributable to the increased activity of matrix metalloproteinase-9 (MMP-9). Patients with acute infarct benefit from the neuroprotective drug edaravone, a free radical scavenger. We examined the mechanisms by which edaravone may help to suppress rtPA-induced brain hemorrhage. Male Wistar rats weighing 250 to 280 g were subjected to 3-hour transient middle cerebral artery occlusion (MCAO) and divided randomly into 3 groups. Immediately after reperfusion, 1 group was intravenously injected with 10 mg/kg rtPA, another with rtPA plus 3 mg/kg edaravone, and the 3rd group received no treatment. We assessed the hemorrhage volume and the activity of MMP-9 in the brain 24 hours postischemia. We also studied the activity of MMP-9, its mRNA expression, and nuclear factor-kappa B (NF-kappaB) activity in rtPA-stimulated human microvascular endothelial cells (HBECs). The degree of hemorrhage and the level of endothelial cell-derived MMP-9 were elevated in rats treated with rtPA alone and attenuated in rats treated with rtPA plus edaravone. In rtPA-stimulated HBECs, edaravone suppressed the activity and mRNA expression of MMP-9 in a dose-dependent manner. Edaravone also inhibited NF-kappaB activation. We demonstrate that edaravone inhibits rtPA-induced cerebral hemorrhage in the ischemic brain of rats via the inhibition of MMP-9 expression in vivo, which is substantiated by inhibition of MMP-9 expression and NF-kappaB activation in HBECs. Edaravone may render thrombolytic therapy safer for the administration of rtPA in patients with ischemic stroke.
Kazuyuki Kuwayama, Kazuhito Matsuzaki, Yoshifumi Mizobuchi, Hideo Mure, Keiko T. Kitazato, Teruyoshi Kageji, Michiyasu Nakao and Shinji Nagahiro : Promyelocytic leukemia protein induces apoptosis due to caspase-8 activation via the repression of NFkB activation in glioblastoma, Neuro-Oncology, Vol.11, No.2, 132-141, 2009.
(Summary)
Promyelocytic leukemia (PML) protein plays an essential role in the induction of apoptosis; its expression is reduced in various cancers. As the functional roles of PML in glioblastoma multiforme (GBM) have not been clarified, we assessed the expression of PML protein in GBM tissues and explored the mechanisms of PML-regulated cell death in GBM cells. We examined the PML mRNA level and the expression of PML protein in surgical GBM specimens. PML-regulated apoptotic mechanisms in GBM cells transfected with plasmids expressing the PML gene were examined. The protein expression of PML was significantly lower in GBM than in non-neoplastic tissues; approximately 10% of GBM tissues were PML-null. The PML mRNA levels were similar in both tissue types. The overexpression of PML activated caspase-8 and induced apoptosis in GBM cells. In these cells, PML decreased the expression of transactivated forms of NFkappaB/p65, and c-FLIP gene expression was suppressed. Therefore, PML-induced apoptosis resulted from the suppression of the transcriptional activity of NFkappaB/p65. PML overexpression decreased phosphorylated IkappaBalpha and nuclear NFkappaB/p65 and increased the expression of the suppressor of cytokine signaling (SOCS-1). A proteasome inhibitor blocked the reduction of activated p65 by PML. The reduction of PML is associated with the pathogenesis of GBM. PML induces caspase-8-dependent apoptosis via the repression of NFkappaB activation by which PML facilitates the proteasomal degradation of activated p65 and the sequestration of p65 with IkappaBalpha in the cytoplasm. This novel mechanism of PML-regulated apoptosis may represent a therapeutic target for GBM.
Toshiyuki Okazaki, Teruyoshi Kageji, Kazuhito Matsuzaki, Hidehisa Horiguchi, Takanori Hirose, Hiroyoshi Watanabe, Toshihiro Ohnishi and Shinji Nagahiro : Primary anaplastic pleomorphic xanthoastrocytoma with widespread neuroaxis dissemination at diagnosis--a pediatric case report and review of the literature., Journal of Neuro-Oncology, Vol.94, No.3, 431-437, 2009.
(Summary)
We report a 5 year-old boy with primary anaplastic pleomorphic xanthoastrocytoma (PXA) with whole neuroaxis dissemination at diagnosis who experienced the sudden onset of generalized convulsion. Head- and spinal magnetic resonance imaging (MRI) showed widespread gadolinium (Gd)-enhanced lesions extending to the bilateral frontal- and medial temporal lobes and the spinal cord. Subsequent MRI study demonstrated that the lesion size increased without any neurological deterioration. Under a histopathologic diagnosis of anaplastic PXA he underwent adjuvant chemotherapy consisting of 12 cycles of carboplatin and vincristine. The patient is alive without any neurological deficits; follow-up MRI showed that the lesions remained stable during 18 months of chemotherapy. We report a very rare pediatric case of primary anaplastic PXA with dissemination involving the entire neuroaxis at the time of diagnosis.
(Keyword)
Astrocytoma / Brain Neoplasms / Child, Preschool / Diagnosis, Differential / Head / Humans / magnetic resonance imaging / Male / Neoplasms, Complex and Mixed / spinal cord / Tomography, X-Ray Computed
Naomi Morita, Masafumi Harada, Masaaki Uno, Shunji Matsubara, Shinji Nagahiro and Hiromu Nishitani : Evaluation of Initial Diffusion-weighted Image Findings in Acute Stroke Patients using a Semiquantitative Score., Magnetic Resonance in Medical Sciences, Vol.8, No.2, 47-53, 2009.
(Summary)
We evaluated the usefulness of rating diffusion-weighted images (DWI) using a semiquantitative score modified from the Alberta Stroke Programme Early CT Score (ASPECTS) to predict deterioration of neurological symptoms in patients with hyperacute ischemic stroke who had undergone thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). We examined 22 patients with acute stroke (14 men, 8 women, mean age 72.5 years) treated with intravenous rt-PA. All were assessed using the National Institutes of Health Stroke Scale (NIHSS) and underwent emergent magnetic resonance (MR) imaging within 3 hours and 24 hours of stroke onset. Patients were divided into a deteriorated group (16 patients), in which NIHSS scores were increased after thrombolysis, and a non-deteriorated group (6 patients). We compared the DWI score, ASPECTS, and volume of hyperintense ischemic lesion on DWI (DWI volume) of the 2 groups and examined correlations between these scores and initial NIHSS score or DWI volume. The DWI score and ASPECTS tended to be lower in the deteriorated group than the non-deteriorated group. In addition, with a cutoff value<or=7, the DWI score could discriminate the deteriorated group from the non-deteriorated group with a sensitivity of 50% and specificity of 87.5%, whereas for ASPECTS, sensitivity was 50% and specificity, 81.2%. The DWI score, ASPECTS, and DWI volume had no correlation with NIHSS score but weak negative correlations with the DWI volume (P<0.01; Spearman's test). Comparing initial NIHSS score with each DWI score and DWI volume, the non-deteriorated group tended to have higher DWI scores and smaller DWI volumes than the deteriorated group, but there was no statistical difference between initial NIHSS and DWI scores. Though the DWI score was not statistically different, the threshold would be set to 6 points or above. Comparing initial DWI score with volume, patients with low DWI scores tended to show large variation in DWI volume and patients with small DWI volume showed large variation in DWI scores. There was no relation between hemorrhagic change and symptoms in either group. The semiquantitative DWI score easily evaluated extent of acute ischemic lesion on DWI and might be used to predict patient outcome after thrombolytic therapy more accurately than ASPECTS or DWI volume.
(Keyword)
Aged / Aged, 80 and over / Diffusion Magnetic Resonance Imaging / Disease Progression / Female / Humans / Male / Middle Aged / Predictive Value of Tests / Sensitivity and Specificity / Severity of Illness Index / Stroke / Tissue Plasminogen Activator / Treatment Outcome
Wataru Sako, Satoshi Goto, Hideki Shimazu, Nagako Murase, Kazuhito Matsuzaki, Tetsuya Tamura, Hideo Mure, Yusuke Tomogane, Noriko Arita, Hiroo Yoshikawa, Shinji Nagahiro and Ryuji Kaji : Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia, Movement Disorders, Vol.23, No.13, 1929-1931, 2008.
(Summary)
Tardive dystonia is a disabling movement disorder as a consequence of exposure to neuroleptic drugs. We followed 6 patients with medically refractory tardive dystonia treated by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for 21 +/- 18 months. At last follow-up, the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score improved by 86% +/- 14%, and the BFMDRS disability score improved by 80% +/- 12%. Bilateral GPi-DBS is a beneficial therapeutic option for the long-term relief of tardive dystonia.
Tomoya Kinouchi, Koichi Satoh, Kazuhito Matsuzaki, Shunji Matsubara and Shinji Nagahiro : 進行性に巨大なvarixを形成した上錐体静脈洞部硬膜動静脈瘻の1例, Surgery for Cerebral Stroke, Vol.36, No.5, 399-403, 2008.
(Summary)
We report a 61-year-old Japanease man with a superior petrosal sinus dural arteriovenous fistula (AVF) with a rapidly growing varix presenting as intracranial hemorrhage. He complained of headache and cerebellar ataxia. A computed tomography (CT) study revealed a huge high-density mass in the left cerebellar hemisphere. The mass had not been detected on a CT scan obtained elsewhere a month earlier. Magnetic resonance imaging revealed a huge flow void in the left cerebellopontine angle, and angiography showed a dural AVF located adjacent to the left superior petrosal sinus. It was supplied by the external carotid arteries and drained via the vein of Galen and a huge varix. After preoperative NBCA embolization of the feeding vessels, he underwent direct surgical ligation of the draining vein. However, as the size of the varix did not decrease and he developed brainstem symptoms, we excised the thrombosed varix. Ours is very rare case of superior petrosal sinus dural AVF resulting in consciousness disturbance due to brainstem compression by a huge varix. We postulate that the development of an intrathrombotic vascular channel and repeated recanalization may have been important factors in the rapid growth of the huge varix.
Naomi Morita, Masafumi Harada, Masaaki Uno, Shunji Matsubara, Shinji Nagahiro and Hiromu Nishitani : Ischemic Findings of T2*-Weighted 3-Tesla MRI in Acute Stroke Patients., Cerebrovascular Diseases, Vol.26, No.4, 367-375, 2008.
(Summary)
We compared ischemic findings on gradient echo-type T(2)*-weighted images at 3-tesla MRI (T(2)*WI) in patients with acute ischemia and major vessel occlusion, and stroke patients with lacunar infarction or branch atheromatous disease. Our study population consisted of 45 patients with acute stroke. They underwent 3-tesla MRI within 12 h of stroke onset. Included were 24 patients (13 men and 11 women, mean age 68 years) with major vessel occlusion and 21 patients (11 men and 10 women, mean age 69 years) with minor infarction such as lacunar infarcts or branch atheromatous disease. We classified vascular ischemic findings of T(2)*WI into 3 sign categories, i.e. artery susceptibility sign, cortical vessel sign (hypointensity and enlargement of the cortical vessels) and brush sign (hypointensity of vessels in the deep white matter). Decreased intensity in the ischemic parenchyma was designated ischemic tissue sign. We compared regions of interest in the hypoperfused area on flow-sensitive alternating inversion recovery (FAIR) images with our vascular ischemic findings. None of the vascular ischemic signs nor the ischemic tissue sign were found in patients with minor vessel disease. All 24 patients with major vessel occlusion manifested the cortical vessel sign, 23 the brush sign. The area with ischemic vessel signs on T(2)*WI was almost as large or somewhat smaller than the hypoperfused area on FAIR images. Compared to the contralateral side, 14 of 24 patients (58.3%) with major vessel occlusion showed decreased intensity in the ischemic parenchyma (ischemic tissue sign). Region of interest measurements on FAIR images demonstrated greater hypoperfusion in the area classified as ischemic tissue sign on T(2)*WI. Ischemic vessel signs and the ischemic tissue sign on T(2)*WI at 3 T would be useful to evaluate the extensive ischemia due to major vessel occlusion and may be correlated with the blood-oxygen-level-dependent effect due to increased deoxyhemoglobin. The ischemic tissue sign may be reflective of severe ischemia.
(Keyword)
Acute Disease / Adult / Aged / Aged, 80 and over / Brain Infarction / Brain Ischemia / Cerebral Angiography / Echo-Planar Imaging / Female / Hemoglobins / Humans / Male / Middle Aged / Severity of Illness Index / Stroke
Kenta Sato, Chiho Sumi-Ichinose, Ryuji Kaji, Kazuhisa Ikemoto, Takahide Nomura, Ikuko Nagatsu, Hiroshi Ichinose, Masayuki Ito, Wataru Sako, Shinji Nagahiro, Ann M. Graybiel and Satoshi Goto : Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia, Proceedings of the National Academy of Sciences of the United States of America, Vol.105, No.34, 12551-12556, 2008.
(Summary)
Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by a childhood onset of fixed dystonic posture with a dramatic and sustained response to relatively low doses of levodopa. DRD is thought to result from striatal dopamine deficiency due to a reduced synthesis and activity of tyrosine hydroxylase (TH), the synthetic enzyme for dopamine. The mechanisms underlying the genesis of dystonia in DRD present a challenge to models of basal ganglia movement control, given that striatal dopamine deficiency is the hallmark of Parkinson's disease. We report here behavioral and anatomical observations on a transgenic mouse model for DRD in which the gene for 6-pyruvoyl-tetrahydropterin synthase is targeted to render selective dysfunction of TH synthesis in the striatum. Mutant mice exhibited motor deficits phenotypically resembling symptoms of human DRD and manifested a major depletion of TH labeling in the striatum, with a marked posterior-to-anterior gradient resulting in near total loss caudally. Strikingly, within the regions of remaining TH staining in the striatum, there was a greater loss of TH labeling in striosomes than in the surrounding matrix. The predominant loss of TH expression in striosomes occurred during the early postnatal period, when motor symptoms first appeared. We suggest that the differential striosome-matrix pattern of dopamine loss could be a key to identifying the mechanisms underlying the genesis of dystonia in DRD.
(Keyword)
Age Factors / Animals / Corpus Striatum / Disease Models, Animal / dopamine / Dystonic Disorders / Humans / Levodopa / Metabolic Networks and Pathways / Mice / Mice, Transgenic / Motor Skills Disorders / Phosphorus-Oxygen Lyases / Tyrosine 3-Monooxygenase
Jun Oto, Atsuhiko Suzue, Daisuke Inui, Yasushi Fukuta, K Hosotsubo, M Torii, Shinji Nagahiro and Masaji Nishimura : Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients, Journal of Anesthesia, Vol.22, No.3, 207-212, 2008.
(Summary)
Proinflammatory and anti-inflammatory cytokines may play a pivotal role in cerebral inflammation, which is implicated in the development of brain injury. Systemic cytokine release is mediated by the sympathetic nervous system and catecholamines. The aim of this study was to investigate which parameters, among plasma levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha) and the levels of the catecholamines, epinephrine and norepinephrine, contribute to the clinical outcome in acute stroke patients. Thirty-seven acute stroke patients (ischemic, n = 19; hemorrhagic, n = 18) were enrolled. All of them were admitted to our hospital within 8 h after stroke onset. Neurological status was evaluated by a modified National Institute of Health Stroke Scale (mNIHSS) on admission and by a modified Rankin Scale (mRS) at 1 month. An mRS score of 3 or more at 1 month was considered to indicate poor outcome. Serum samples for the cytokine and catecholamine measurements were collected on admission. Plasma levels of IL-1beta, IL-6, IL-10, and TNF-alpha were determined by an enzyme-linked immunosorbent assay (ELISA) method and epinephrine and norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC). In the ischemic stroke patients, poor outcome was noted in 9 (47%). There were no significant differences in cytokine or catecholamine concentrations between patients with poor and good outcomes, and there was no association between clinical outcome and cytokine and catecholamine concentrations. In the hemorrhagic stroke patients, poor outcome was noted in 10 (56%). IL-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). In ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.
H Liu, KT Kitazato, Masaaki Uno, Kenji Yagi, Yasuhisa Kanematsu, Tetsuya Tamura, Yoshiteru Tada, Tomoya Kinouchi and Shinji Nagahiro : Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia: in-vivo and in-vitro studies, Journal of Hypertension, Vol.26, No.7, 1435-1445, 2008.
(Summary)
Angiotensin II type 1 (AT1) receptor blockers decrease ischemia by mechanisms dependent on and independent of arterial blood pressure in hypertensive rats and AT1-R knockout mice, respectively. However, the detailed mechanisms underlying the effects of AT1 receptor blockers remain unclear. To elucidate the systemic and focal effects of AT1 receptor blockers against cerebral ischemia in in-vivo and in-vitro studies. Normotensive Wistar rats were treated for 2 weeks with 0.5 or 1 mg/kg candesartan cilexetil and then subjected to 2-h middle cerebral artery occlusion-reperfusion. Human umbilical endothelial cells were stimulated with the active form of candesartan and angiotensin II in the absence and presence of an angiotensin II type 2 (AT2) receptor antagonist. In candesartan-pretreated hypotensive and nonhypotensive rats, blood pressure was moderately increased during middle cerebral artery occlusion and fell gradually to the baseline after the reperfusion; it remained elevated in the control even after the reperfusion occlusion. Candesartan treatment resulted in a decrease in the cortical infarct volume and oxidative damage, the hypoxic status was improved, and the expression of repair-associated and growth-associated proteins in the cortical penumbra was augmented. Candesartan also increased the eNOS mRNA level and the lumen size of the middle cerebral artery. In human umbilical endothelial cells, candesartan increased the eNOS protein level AT2-R dependently, inhibited the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and angiotensin II-induced intracellular reactive oxygen species and nitric oxide, and promoted the extracellular release of nitric oxide, suggesting that it augmented the bioavailability of nitric oxide. Among the mechanisms candesartan exerts in its protection against cerebral ischemia, restoration of endothelial function may represent an attractive therapeutic goal to address cerebral ischemia.
(Keyword)
Angiotensin II Type 1 Receptor Blockers / Animals / Benzimidazoles / Biphenyl Compounds / Brain Ischemia / Disease Models, Animal / Endothelium, Vascular / Ligation / Middle Cerebral Artery / Nitric Oxide / Nitric Oxide Synthase Type II / Nitric Oxide Synthase Type III / Oxidative Stress / Rats / Rats, Wistar / Reactive Oxygen Species / Reperfusion Injury / Tetrazoles / Vasodilation
Yoshifumi Mizobuchi, Kazuhito Matsuzaki, Kazuyuki Kuwayama, K Kitazato, Hideo Mure, Teruyoshi Kageji and Shinji Nagahiro : REIC/Dkk-3 induces cell death in human malignant glioma, Neuro-Oncology, Vol.10, No.3, 244-253, 2008.
(Summary)
The progression of glioma to more malignant phenotypes results from the stepwise accumulation of genetic alterations and the consequent disruption of the apoptotic pathway and augmentation of survival signaling. REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of the growth of several human cancers; however, to date it has not been identified in brain tumors. We compared the gene and protein expression of REIC/Dkk-3 in human malignant glioma and normal brain tissues using quantitative real-time PCR, Western blotting, and immunohistochemistry. We also performed small interfering REIC/Dkk-3 (siREIC/Dkk-3) knockdown and REIC/Dkk-3 overexpression experiments to examine the role of REIC/Dkk-3 in human malignant glioma cells in vitro. In brain tissue from patients with malignant glioma, the gene and protein expression of REIC/Dkk-3 was lower than in normal brain tissue and was related to the malignancy grade. In the primary glioblastoma cell line, REIC/Dkk-3 transfection led to apoptosis owing to the activation of phosphorylated JUN, caspase-9, and caspase-3 and the reduction of beta-catenin; in REIC/Dkk-3 knockdown experiments, cell growth was augmented. Our results suggest that REIC/Dkk-3 regulates the growth and survival of these cells in a caspase-dependent and -independent way via modification of the Wnt signaling pathway. Our work is the first documentation that the gene and protein expression of REIC/Dkk-3 is down-regulated in human malignant glioma. Our demonstration of the mechanisms underlying REIC/Dkk-3-induced cell death indicates that REIC/Dkk-3 plays a pivotal role in the biology of human malignant glioma and suggests that REIC/Dkk-3 is a promising candidate for molecular target therapy.
Tomoya Kinouchi, Atsuhiko Suzue, Masaaki Uno and Shinji Nagahiro : もやもや病疑診例の母親から生まれたもやもや病確診例の姉妹の1家系, Japanese Journal of Stroke, Vol.30, No.3, 505-510, 2008.
Masaaki Uno, Atsuhiko Suzue, Kyoko Nishi, Naomi Morita, Masafumi Harada, Yuishin Izumi, Shunya Nakane and Shinji Nagahiro : Diagnosis and Treatment in Stroke Center of Tokushima University Hospital : Efficacy of 3 Tesla Stroke MRI(<Topic> Stroke Care Unit, Stroke Center), Surgery for Cerebral Stroke, Vol.35, No.6, 427-431, 2007.
(Summary)
After the stroke care unit of Tokushima University hospital was established in November 1999, stroke MRI (diffusion-, perfusion-weighted image, MRA) was performed to initially evaluate stroke patients, except for SAH. Since April 2004, 3 tesla MRI has been used for stroke MRI, and T2^* weighted image was added to routine study of stroke MRI. 3 tesla stroke MRI can reduce examination time and also take functional MR images, which yield important information for diagnosis and treatment decisions. The combination of our stroke center and rehabilitation hospital is a key factor in improving patients' outcomes for acute rehabilitation and improving quality of life.
Atsuhiko Suzue, Masaaki Uno, KT Kitazato, Kyoko Nishi, Kenji Yagi, Hao Liu, Tetsuya Tamura and Shinji Nagahiro : Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis inn relation to oxidized low-density lipoprotein and plaque vulnerability, Journal of Vascular Surgery, Vol.46, No.5, 870-875, 2007.
(Summary)
Although carotid endarterectomy (CEA), the gold standard in stroke prevention, has been performed in the late stage after the insult, its optimal timing remains unclear. Using biomarkers in plaque and plasma, we evaluated oxidative stress and plaque vulnerability between early and late CEA in symptomatic patients. We compared symptomatic stroke patients who underwent early CEA within 4 weeks of the last insult (group A; n = 15) with those who received CEA in the late stage beyond 4 weeks from the last symptom (group B; n = 57). They were divided into vulnerable (group Av, n = 13; group Bv, n = 33) and stable (group As, n = 2; group Bs, n = 24) subgroups according to the pathologic findings on their plaques. We studied the relationships among their primary symptoms, clinical findings, oxidized low-density lipoprotein levels, and gelatinase A (matrix metalloproteinase [MMP]-9) activity in their plaques and plasma. Group A had a variety of symptoms; there was no difference in the outcome of CEA between groups A and B. The plaque and plasma oxidized low-density lipoprotein levels were higher in group A than in group B (P < .05). The incidence of pathologically vulnerable plaque was higher in group A than in group B. Plaque oxidized low-density lipoprotein levels and MMP-9 activity were similar in group Av and group Bv and were higher in those groups than in group As and Bs. We first demonstrated that vulnerable plaques in patients subjected to early CEA manifested a remarkable increase in oxidized low-density lipoprotein and MMP-9 activation. Our findings suggest that early CEA may be beneficial in the aspect of oxidative stress.
Naomi Morita, Masafumi Harada, Masaaki Uno, Hiromu Nishitani and Shinji Nagahiro : Diagnosis of acute stroke patients: using MRI as the first selected modality, Japanese Journal of Clinical Radiology, Vol.52, 1663-1669, 2007.
A. M. Jamos, Shinji Nagahiro, k.T. Kitazato, T. Tamura, H. Abdel, Masayuki Shono and K. Satoh : Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats, Journal of Neurosurgery, Vol.107, No.2, 405-411, 2007.
(Summary)
Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague-Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery-olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohistochemically by using antibodies against endothelial nitric oxide synthase, alpha-smooth muscle actin, macrophages, and matrix metalloproteinase-9. Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.
Ayako Tamura, Takako Ichihara, Shinjiro Takata, Takako Minagawa, Yumi Kuwamura, Takae Bando, Natsuo Yasui and Shinji Nagahiro : Study on factors related to loss of lower extremity muscle mass in elderly acute stroke patients, JNI : The Journal of Nursing Investigation, Vol.6, No.1, 23-27, 2007.
(Summary)
The present study investigated the factors contributing to the loss of upper and lower extremity muscle mass in three elderly stroke patients with right hemiplegia in whom our rehabilitation program could not be performed at 1‐2 weeks after onset. The results revealed common factors such as prolonged accurate microinjection of hypotensive agents, severe hemiplegia(Brunnstrom stage I or Ⅱ), diarrhea and delayed initiation of tube feeding at 3 to 8 days after onset. With regard to individual differences, while all patients were recovering in bed, the degree of decrease in muscle mass varied among patients because they moved their extremities differently.
(Keyword)
elderly / acute stroke patients / loss of lower extremity muscle mass / related factors
河北 直也, Koji Fujita, Takao Mitsui, Yuishin Izumi, Atsuhiko Suzue, Masaaki Uno, Koichi Satoh, Shinji Nagahiro, Hirotsugu Yamada, Naomi Morita and Ryuji Kaji : 3 Tesla T2^*-weighted MRI demonstrating an intra-MCA embolus in a young adult with cerebral embolism, Japanese Journal of Stroke, Vol.29, No.3, 469-473, 2007.
Ayako Tamura, Takako Minagawa, Shinjiro Takata, Takako Ichihara, Yumi Kuwamura, Takae Bando, Hiroko Kondo, Natsuo Yasui and Shinji Nagahiro : Effects of intervention with back-lying exercises with bent knees pointing upwards to prevent disuse muscle atrophy in patients with post-stroke hemiplegia, JNI : The Journal of Nursing Investigation, Vol.5, No.2, 53-58, 2007.
(Summary)
The present study measured lower extremity muscle mass using DXA (Dual energy X-ray Absorptiometry) in order to verify the effectiveness of intervention with a series of movements, including lying hip raise exercise with bent knees pointing upwards, among bedridden patients with post-stroke hemiplegia in the acute post-stroke period. Subjects in the intervention group were required to perform 10 repetitions of a series of back-lying exercises once a day with researchers, in addition to the exercises performed by those in a control group. The first measurement of muscle mass was conducted at three to five days after onset, and the second measurement was conducted seven days after the first. Muscle mass in the lower extremities was reduced by approximately 600g (decrease rate : 9%)on the paralyzed side and by 280g on the non-paralyzed side(decrease rate: 5%)in one week in the Brunnstrom stage ≤ II subgroup(site of measurement : lower extremities) (n＝8) of the control group (n＝23). The decrease in muscle mass in the Brunnstrom stage ≤ II subgroup (n＝4) of the intervention group (n＝15) was approximately 260g on the paralyzed side (decrease rate : 5%) and approximately 280g (decrease rate : 5%)on the non-paralyzed side. Thus, muscle mass decreased on both sides, and this occurred regardless of degree of paralysis. Comparison of the Brunnstrom stage ≥ III subgroups between the control and intervention groups also confirmed that the decease in muscle mass was smaller in the latter group. Thus, it was confirmed that back-lying exercises combining lower extremity movements, including hip raises with bent knees pointing upwards, prevented the decrease in lower extremity muscle mass on the paralyzed side in post-stroke patients. The present study also suggests that these exercise movements can be applied to preventive care for bedridden patients with other severe diseases.
(Keyword)
effects of intervention / acute post-stroke period / lower extremity muscle / prevent disuse muscle atrophy / hip raise exercises
Teruyoshi Kageji, Shinji Nagahiro, Kazuhito Matsuzaki, Yasuhisa Kanematsu, M Nakatani, Y Okamoto and Tsutomu Watanabe : Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated primary intracranial chriocarcinoma: case report, Journal of Neuro-Oncology, Vol.83, No.2, 199-204, 2007.
(Summary)
We report a 17-year-old male with disseminated intracranial choriocarcinoma at the basal ganglia whose consciousness level was very low at diagnosis. He received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy prior to radical excision of the tumor. Postoperatively he was treated with three courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and etoposide (VP-16)) and peripheral blood stem-cell transplantation. This combination of therapies resulted in tumor regression on MRI and remarkable improvement in his neurological condition. Ours is the first report of the effectiveness of NAT followed by radical surgery in a patient with disseminated primary intracranial choriocarcinoma.
Masaaki Uno, Atsuhiko Suzue, Kyoko Nishi and Shinji Nagahiro : Hemodynamic cerebral ischemia during carotid endarterectomy evaluated by intraoperative monitoring and post-operative diffusion-weighted imaging, Neurological Research, Vol.29, No.1, 70-77, 2007.
(Summary)
We used the result of monitoring to evaluate patients with post-operative neurological deficits attributable to hemodynamic cerebral ischemia owing to cross-clamping of the carotid artery. We evaluated 131 carotid endarterectomy (CEA) procedures performed on 118 patients, 96 men and 22 women ranging in age from 38 to 82 years (mean: 67.1 years). For monitoring, we used a combination of somatosensory evoked potential (SEP), functional dynamic electroencephalography (EEG), near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD). Patients who awoke with neurological deficits after CEA immediately underwent diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA). In 30 of the 131 procedures (22.9%), intraoperative monitoring disclosed abnormalities after cross-clamping of the internal carotid artery (ICA). In two of these 30 patients, shunt was not introduced, because of full recovery of monitoring after blood pressure increasing, however, one patient demonstrated transient ischemic attack (TIA). In six of remaining 28 patients who need shunt, transient hemodynamic cerebral ischemia occurred, however, all patients recovered gradually within 18 hours after CEA. No new lesions were detected on post-operative DWI of the seven patients and MRA demonstrated good patency of the carotid artery. The other 101 patients whose intraoperative monitoring after cross-clamping of the ICA did not disclose abnormalities demonstrated no hemodynamic TIA. Hemodynamic ischemia owing to cross-clamping of the ICA is rare in patients treated by CEA. However, in patients manifesting neurological deficits upon awakening from CEA, DWI and MRA should be performed immediately to facilitate their prompt treatment.
(Keyword)
Aged / Brain Ischemia / Carotid Artery, Internal / Cerebral Arteries / Cerebrovascular Circulation / Diffusion Magnetic Resonance Imaging / Early Diagnosis / Electroencephalography / Endarterectomy, Carotid / Evoked Potentials, Somatosensory / Female / Humans / Male / Middle Aged / Monitoring, Intraoperative / Postoperative Complications / Predictive Value of Tests / Recovery of Function / near infrared spectroscopy / Ultrasonography, Doppler, Transcranial
Naomi Morita, Masafumi Harada, Masaaki Uno, Hiromu Nishitani and Shinji Nagahiro : The usefulness and problem for MR I examination by using clinical 3T-MRI, DIGITAL MEDICINE, Vol.7, 6-9, 2007.
266.
Satoshi Goto, K Yamada, Hideki Shimazu, Nagako Murase, Kazuhito Matsuzaki, Tetsuya Tamura, Shinji Nagahiro, J Kuratsu and Ryuji Kaji : Impact of bilateral pallidal stimulation on DYT1-generalized dystonia in Japanese patients, Movement Disorders, Vol.21, No.10, 1785-1787, 2006.
(Summary)
Early-onset generalized dystonia attributable to a DYT1 gene mutation is a hyperkinetic movement disorder that responds poorly to pharmacotherapy. In this video brief, we show that continuous bilateral stimulation of the globus pallidus internus produced sustained and marked improvements in the motor symptoms and functional disabilities of Japanese patients with DYT1-generalized dystonia.
Ayako Tamura, Takako Ichihara, Shinjiro Takata, Takako Minagawa, Yumi Kuwamura, Takae Bando, Hiroko Kondo, Natsuo Yasui and Shinji Nagahiro : Changes in lower extremity muscle mass among bedridden patients with post-stroke hemiplegia in the acute post-stroke period, JNI : The Journal of Nursing Investigation, Vol.5, No.1, 18-21, 2006.
(Summary)
The present study analyzed16patients who were bedridden for one week immediately after onset of post-stroke hemiplegia. We used DXA(dual energy X-ray absorptiometry)to determine changes in muscle mass in the lower extremities on both paralyzed and non-paralyzed sides. The first measurement was conducted 3 to 5 days after the onset, and the second measurement was conducted 7 days after the first. Muscle mass in the lower extremities was reduced by approximately 600g (9%) on the paralyzed side with and by 200g on the non-paralyzed side (3%) in the Brunnstrom stage≤II group (n＝5). Although the decrease of muscle mass in the Brunnstrom stage≥III group(n＝11, relatively slight degree of functional motion impairment)was not significant, a decrease of approximately 300g (decrease rate : 5%)was observed on the paralyzed side and approximately 100g (decrease rate : 1．5%)was seen on the non-paralyzed side. Hence, muscle mass declined on both sides, and this occurred regardless of degree of paralysis. The findings suggested that conventional range of motion exercises, functional position maintenance, and postural changes are inadequate to prevent disuse muscle atrophy in post-stroke patients ; thus, it is necessary to develop a new rehabilitation program which adopts different exercises such as trunk motion, even for patients in the acute stage after stoke onset.
(Keyword)
acute post-stroke period / hemiplegia / lower extremity muscle / disuse muscle atrophy / dual energy X-ray Absorptiometry(DXA)
Ryoma Morigaki, Masaaki Uno, Atsuhiko Suzue and Shinji Nagahiro : Hemichorea due to hemodynamic ischemia associated with extracranial carotid artery stenosis. Report of two cases., Journal of Neurosurgery, Vol.105, No.1, 142-147, 2006.
(Summary)
In this paper the authors describe two patients with recurrent hemiparesis and limb shaking that gradually progressed to hemichorea. Cerebral angiography confirmed severe unilateral internal carotid artery stenosis (95%) contralateral to the hemichorea. The cerebral blood flow, assessed using N-isopropyl-p-(iodine-123) iodoamphetamine single-photon emission computed tomography (SPECT), disclosed markedly decreased vascular reserves in both patients. After carotid endarterectomy was performed, the hemichorea gradually subsided and SPECT confirmed increased cerebral perfusion. The results in these cases indicate that surgical revascularization is effective for hemichorea due to cerebral ischemia with reduced vascular reserve.
Teruyoshi Kageji, Shinji Nagahiro, Kazuhito Matsuzaki, Yoshifumi Mizobuchi, H Toi, Y Nakagawa and H Kumada : Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome, International Journal of Radiation Oncology*Biology*Physics, Vol.65, No.5, 1446-1455, 2006.
(Summary)
To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n = 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively.
Mami Hanaoka, Koichi Satoh, Junichiro Satomi, Shunji Matsubara, Shinji Nagahiro, Osamu Takimoto and Masaaki Obayashi : Microcatheter pull-up technique in the transvenous embolization of an isolated sinus dural arteriovenous fistula, Journal of Neurosurgery, Vol.104, No.6, 974-977, 2006.
(Summary)
The authors describe a novel technique involving the use of a gooseneck snare for microcatheterization of isolated sinus dural arteriovenous fistulas (DAVFs). In some patients the inferior petrosal and transverse-sigmoid sinuses, the route of transvenous embolization (TVE) for DAVF, are separated by several channels. Even if a guidewire can be passed over the occluded portion and the affected sinus can be accessed, one may not necessarily be able to insert a microcatheter. The authors report on three patients who underwent successful microcatheterization via a novel pull-up technique, which makes use of a gooseneck snare to perform TVE even in very difficult circumstances.
(Keyword)
Aged / Angioplasty / Central Nervous System Vascular Malformations / Cranial Sinuses / Embolization, Therapeutic / Female / Humans / Male / Middle Aged
Masaaki Uno, Kyoko Nishi, Atsuhiko Suzue, Shinji Manabe, Shunji Matsubara, Koichi Satoh and Shinji Nagahiro : Strategy and Outcome in Patients with Unruptured Cerebral AVM(<Topics>Unruptured Arteriovenous Malformations), Surgery for Cerebral Stroke, Vol.34, No.3, 157-162, 2006.
(Summary)
The treatment of unruptured cerebral arteriovenous malformation (AVM) is still controversial. We have been treating these patients according to the Spetzler & Martin (S&M) grading system. We retrospectively evaluated the outcomes of 46 unruptured AVM patients and also evaluated the bleeding rate during follow-up period. Recently we also started performing functional MRI, trac-tography, and 3-dimensional (3D) angiography for these patients before treatment. In 18 of 22 patients in S&M Grade I and II, AVMs were surgically removed and the outcome was good. Six of 9 patients in S&M Grade IV and V, were conservatively treated. In patients in S&M Grade III, various treatments were performed according to the location of the AVM, but all their outcomes were favorable. The rate of permanent surgical complications was 15.3% in 26 unruptured AVM patients. Based on our treatment results, aggressive treatment should be performed in patients with S&M Grade I and II. However, treatment decisions must be carefully considered based on functional MRI, tractography of AVM, and 3D angiography.
K Yamada, Satoshi Goto, Kazuhito Matsuzaki, Tetsuya Tamura, Nagako Murase, Hideki Shimazu, Shinji Nagahiro, J Kuratsu and Ryuji Kaji : Alleviation of camptocormia by bilateral subthalamic nucleus stimulation in a patient with Parkinson's disease, Parkinsonism & Related Disorders, Vol.12, No.6, 372-375, 2006.
(Summary)
Camptocormia, known also as "bent spine syndrome", is characterized by involuntary truncal flexion of the thoraco-lumbar spine that appears in the sitting or standing position. Although Parkinson's disease (PD) is the most frequent etiologic factor, this postural disorder responds poorly to levodopa or other medications. We report a PD patient in whom chronic bilateral subthalamic nucleus stimulation produced a striking alleviation of camptocormia.
K Yamada, Satoshi Goto, Kazuhito Matsuzaki, Shinji Nagahiro, Nagako Murase, Hideki Shimazu, Ryuji Kaji, J Kuratsu and Y Ushio : Psychiatric symptoms and subthalamic nucleus stimulation in Parkinson's disease. A retrospective study in our Japanese patients, Neuromodulation, Vol.9, No.2, 107-114, 2006.
(Summary)
Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty-five patients underwent bilateral STN stimulation. Pre- and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab-England (S-E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug-induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients' psychiatric symptoms. Postoperative S-E score showed a significant improvement compared to the pretreatment baseline in both of "on" and "off" medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S-E score in "on" state (p < 0.01). Preoperative score for intellectual impairment was only a significant predictor of worse postoperative ADL in "off" state. Conclusions. The markedly lower dose of levodopa may suggest ethnic characteristics of our Japanese patients with respect to tolerance for antiparkinsonian medications. Preoperative manifestation of drug-induced psychosis and cognitive dysfunction were the major factor that strikingly suppressed daily activities after STN stimulation.
Jamous A Mohammad, Shinji Nagahiro, Kitazato T Keiko, Tetsuya Tamura, Kazuyuki Kuwayama and Koichi Satoh : Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II, --- experimental study of the effect of hormone replacement therapy in rats ---, Journal of Neurosurgery, Vol.103, No.6, 1052-1057, 2005.
(Summary)
The increased incidence of cerebral aneurysms in postmenopausal women appears to be related to low levels of circulating estrogen. Using a rat model of aneurysm induction, the authors found that oophorectomy increased the incidence of experimental cerebral aneurysms (Part I in this issue). In the current study they examined the effects of hormone replacement therapy (HRT) on the formation of cerebral aneurysms in rats. Forty-five female Sprague-Dawley rats were divided into three equal groups. The animals in Groups A and B were subjected to a cerebral aneurysm induction procedure (renal hypertension and right common carotid artery ligation) followed 1 month later by bilateral oophorectomy. After an additional week the rats in Group A received 17beta estradiol continuous-release pellets. The rats in Group C served as controls. Three months after the aneurysm induction procedure, all the rats were killed and vascular corrosion casts of their cerebral arteries were prepared and checked for aneurysmal changes. Using a scanning electron microscope, the authors recorded aneurysmal changes as endothelial changes alone (Stage I), endothelial changes with intimal pad elevation (Stage II), and saccular aneurysm formation (Stage III). Aneurysmal changes (Stages I, II, and III) occurred in one third of rats that had undergone oophorectomy and were receiving HRT (Group A), compared with 87% of the rats that had undergone oophorectomy but did not receive HRT (Group B). Although most of the aneurysmal changes identified in Group A rats were limited to Stage I or II, most changes in Group B animals were identified as saccular dilation (Stage III). The findings demonstrated the significant protective role of estrogen against the formation and progression of cerebral aneurysms. It appears to be related to the beneficial effects of estrogen on the function and growth of endothelial cells, which play a major role in preserving the integrity of the vascular wall.
Jamous A Mohammad, Shinji Nagahiro, Kitazato T Keiko, Junichiro Satomi and Koichi Satoh : Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part I, --- experimental study of the effect of oophorectomy in rats ---, Journal of Neurosurgery, Vol.103, No.6, 1046-1051, 2005.
(Summary)
Estrogen has been shown to play a central role in vascular biology. Although it may exert beneficial vascular effects, its role in the pathogenesis of cerebral aneurysms remains to be determined. To elucidate the role of hormones further, the authors examined the effects of bilateral oophorectomy on the formation and progression of cerebral aneurysms in rats. Forty-five female, 7-week-old Sprague-Dawley rats were divided into three equal groups. Group I consisted of intact rats (controls). To induce cerebral aneurysms, the animals in Groups II and III were subjected to ligation of the right common carotid and bilateral posterior renal arteries. One month later, the rats in Group II underwent bilateral oophorectomy. Three months after the experiment began all animals were killed and cerebral vascular corrosion casts were prepared and screened for cerebral aneurysms by using a scanning electron microscope. Plasma was used to determine the level of estradiol and the gelatinase activity. Hypertension developed in all rats except those in the control group. The estradiol level was significantly lower in Group II than in the other groups (p < 0.01). The incidence of cerebral aneurysm formation in Group II (60%) was three times higher than that in Group III (20%), and the mean size of aneurysms in Group II (76 +/- 27 microm, mean +/-standard deviation) was larger than that in Group III (28 +/- 4.6 microm) (p < 0.05). No aneurysm developed in control animals (Group I), and there was no significant difference in plasma gelatinase activity among the three groups. The cerebral aneurysm model was highly reproducible in rats. Bilateral oophorectomy increased the susceptibility of rats to aneurysm formation, indicating that hormones play a role in the pathogenesis of cerebral aneurysms.
Kenji Yagi, Koichi Satoh, Junichiro Satomi, Shunji Matsubara and Shinji Nagahiro : Evaluation of Aneurysm Stability After Endovascular Embolization With Guglielmi Detachable Coils, --- Correlation Between Long-Term Stability and Volume Embolization Ratio ---, Neurologia Medico-Chirurgica, Vol.45, No.11, 561-565, 2005.
(Summary)
The correlation between volume embolization ratio (VER), the percentage of aneurysm volume occupied by coils, and aneurysm stability after endovascular treatment with platinum coils was studied in 86 patients who underwent embolization of 88 cerebral saccular aneurysms with standard platinum coils between March 1997 and January 2003. Radiographic follow up was possible of 62 aneurysms with greater than 70% obliteration on immediate post-procedure angiograms for more than 6 months. Immediate post-procedure evaluation found that 12 of 14 small (<4 mm), 12 of 38 medium (4-<10 mm), and two of 10 large (> or =10 mm) aneurysms had high (> or =25%) VER. In addition, the VER was high in 22 of 40 aneurysms with small (<4 mm) and four of 22 with wide necks (> or =4 mm). Evaluation of 57 aneurysms at 6 months after coil embolization found recanalization in two of 25 aneurysms with high VER and 21 of 32 with low (<25%) VER, indicating that aneurysms with high VER are significantly more stable than those with low VER (p < 0.01). VER strongly affects aneurysm stability, so high VER is desirable and a useful predictor of aneurysm stability.
Kazuhito Matsuzaki, Masaaki Uno, Teruyoshi Kageji, Takanori Hirose and Shinji Nagahiro : Anaplastic ganglioglioma of cerebellopontine angle: A case report and review of literatures, Neurologia Medico-Chirurgica, Vol.45, No.11, 591-595, 2005.
(Summary)
A 64-year-old woman presented with a rare anaplastic ganglioglioma in the right cerebellopontine angle manifesting as dizziness persisting for 2 weeks. Preoperative magnetic resonance (MR) imaging revealed a partially enhanced cystic lesion of the right cerebellopontine angle. The tumor was subtotally removed through a right lateral suboccipital craniectomy. The tumor was thought to originate from the brain stem with exophytic growth into the right cerebellopontine angle. Histological examination showed neoplastic ganglional and glial cells with anaplastic features such as mitosis, pleomorphism, and endothelial proliferation. The MIB-1 labeling index of the glial components was 40% to 60%. The diagnosis was anaplastic ganglioglioma (World Health Organization grade IV). She received postoperative radiotherapy but died of respiratory failure with tumor recurrence 11 months after the operation. Gangliogliomas usually have a good prognosis. Histological features of anaplasia and a high MIB-1 labeling index may be predictive of a poor clinical outcome.
Masaaki Uno, Keiko T. Kitazato, Atsuhiko Suzue, Kazuhito Matsuzaki, Masahumi Harada, Hiroyuki Itabe and Shinji Nagahiro : Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction, Free Radical Biology and Medicine, Vol.39, No.8, 1109-1116, 2005.
(Summary)
We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups: GI (n = 24) had cortical lesions, and GII (n = 27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n = 13; GIIa, n = 14) and its efficacy was studied by comparing their plasma OxLDL, S-100B, and MnSOD levels to those in patients without edaravone (GIb, n = 11, GIIb, n = 13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa than GIb patients (0.177 +/- 0.024 ng/microg apoB vs 0.219 +/- 0.026, P < 0.05). In GIIa patients, pre- and posttreatment plasma OxLDL was not significantly different (0.156 +/- 0.013 vs 0.152 +/- 0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (P < 0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb patients. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.
Masaaki Uno, Keiko T Kitazato, Atsuhiko Suzue, Hiroyuki Itabe, Liu Hao and Shinji Nagahiro : Contribution of an imbalance between oxidant-antioxidant systems to plaque vulnerability in patients with carotid artery stenosis, Journal of Neurosurgery, Vol.103, No.3, 518-525, 2005.
(Summary)
Reactive species of oxygen and nitrogen mediate the oxidative modification of low-density lipoprotein (LDL). Oxidation of LDL is inhibited by endogenous radical scavenging enzymes such as manganese superoxide dismutase (SOD) and Cu-ZnSOD that catalyze dismutation of oxygen to H2O2. Low-molecular antioxidants such as uric acid regulate the inactivation that appears to be linked to an increase in peroxynitrite resulting in oxidized LDL (OxLDL) elevation. The authors evaluated whether a focal imbalance between pro- and antioxidant systems induces plaque vulnerability in patients with carotid artery (CA) stenosis. Carotid artery plaques obtained in 35 patients who had undergone carotid endarterectomy were classified as vulnerable or stable based on histopathological findings. In vulnerable plaques, OxLDL, measured using enzyme-linked immunosorbent assay, was significantly higher (p < 0.01) and SOD activity significantly lower than in stable plaques (p < 0.05). The plaque and plasma OxLDL levels were inversely correlated with plaque SOD activity (p < 0.01). The physiological uric acid level in all plaques was one fourth to one eighth of that in plasma and appeared to be unable to protect Cu-ZnSOD from degradation by H2O2. Immunohistochemical analysis showed increased peroxynitrite and OxLDL in vulnerable plaques. There was a significant correlation between plaque and plasma OxLDL levels (p < 0.01). Analysis of the results suggests that a focal imbalance between pro- and antioxidant defense systems in patients with CA plaques induces an increase in plaque OxLDL levels and consequent plaque instability, contributing to high levels of plasma OxLDL.
Toshiyuki Okazaki, Junichiro Satomi, Koichi Satoh, Motohiro Hirasawa and Shinji Nagahiro : Rescue Revascularization Therapy With a Stent-in-Stent Technique for Acute Intracranial Internal Carotid Artery Occlusion, --- Case Report ---, Neurologia Medico-Chirurgica, Vol.45, No.5, 253-258, 2005.
(Summary)
A 45-year-old woman presented with progressive stroke due to occlusion of the left internal carotid artery at the level of the cavernous portion (C3/C4). Revascularization was achieved by stent deployment following percutaneous transluminal angioplasty. Stent thrombosis occurred 7 days after primary stenting; it was successfully treated with the stent-in-stent technique. The patient was able to return to her independent life with no sequelae except for slight hemiparesis. In combination with appropriate antiplatelet treatment, the stent-in-stent technique should be considered as a rescue option in patients with re-occlusion of an intracranial stent.
Jamous A Mohammad, Shinji Nagahiro, Kitazato T Kitazato, Koichi Satoh and Junichiro Satomi : Vascular corrosion casts mirroring early morphological changes that lead to the formation of saccular cerebral aneurysm: an experimental study in rats, Journal of Neurosurgery, Vol.102, No.3, 532-535, 2005.
(Summary)
The formation of cerebral aneurysms involves complex processes and little is known about the mechanisms by which they originate, grow, and rupture. The purpose of this study was to identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysms. Twenty male Sprague-Dawley rats were subjected to cerebral aneurysm induction (renal hypertension and right common carotid artery ligation); 10 intact rats served as the control group. The animals were killed after 2 months, and a vascular corrosion cast of their cerebral arteries was prepared and screened for aneurysm development by using a scanning electron microscope. Sequential morphological changes observed at the cerebral artery bifurcation in response to hemodynamic shear stress included endothelial changes, intimal pad elevation, and saccular dilation. Endothelial cell changes were the first observed morphological changes; they were followed by various degrees of artery wall dilation. No aneurysmal changes developed in any of the control rats. Of the 20 surgically treated rats, 11 displayed aneurysmal changes. In five of these animals only changes in the endothelial cell imprints could be identified. In the other six rats morphological changes in endothelial cells were associated with different stages of aneurysmal dilation. This is the first study to demonstrate in vivo early morphological changes that lead to the formation of cerebral aneurysms. The morphological findings indicate the principal role of endothelial cells in the pathogenesis of cerebral aneurysms and suggest that hemodynamic shear stress and blood flow patterns may precipitate these early changes.
Junichiro Satomi, Koichi Satoh, Shunji Matsubara, Norio Nakajima and Shinji Nagahiro : Angiographic Changes in Venous Drainage of Cavernous Sinus Dural Arteriovenous Fistulae after Palliative Transarterial Embolization or Observational Management, --- A Proposed Stage Classification ---, Neurosurgery, Vol.56, No.3, 494-502, 2005.
(Summary)
We assessed whether angiographic changes in venous drainage patterns occur over time in cavernous sinus dural arteriovenous fistulae (dAVFs) without a complete cure. We classified 65 cavernous sinus dAVFs into three types on the basis of initial angiographic findings. In Type 1, both anterior and posterior drainage routes were open; in Type 2, the posterior drainage route was closed, whereas the anterior drainage route was open; and in Type 3, both the posterior and anterior drainage routes were closed. Of the 65 dAVFs, 40 were of Type 1, 21 of Type 2, and 4 of Type 3. During the follow-up period, 17 of the dAVFs that were treated palliatively with transarterial embolization (n = 11) or monitored without therapy (n = 6) demonstrated angiographic changes. In these 11 patients, there was a change in the venous drainage pattern from Type 1 to Type 2 (n = 5), from Type 2 to Type 3 (n = 3), and from Type 1 to Type 3 (n = 3). One of 11 had a conversion into a lesion with cortical venous drainage. The remaining 6 dAVFs (4 with observational management, 2 with transarterial embolization) demonstrated closure of the fistula; in 5 of these, the affected cavernous sinus was not depicted on follow-up angiograms. In some cavernous sinus dAVFs with palliative transarterial embolization or observational management, there was a change in the venous drainage patterns, consisting of a decrease in the number of venous drainage routes. There was a trend for the posterior route to close before the anterior drainage or cortical drainage route. This suggests the occurrence of a staged progression in a regular direction in cavernous sinus dAVFs. Without treatment aiming at a complete cure, most cavernous sinus dAVFs can behave benignly, with a low possibility of development of cortical venous reflux during follow-up.
Masaaki Uno, Masahumi Harada, Osamu Takimoto, Keiko T Kitazato, Atsuhiko Suzue, Kazuhide Yoneda, Naomi Morita, Hiroyuki Itabe and Shinji Nagahiro : Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement, Neurological Research, Vol.27, No.1, 94-102, 2005.
(Summary)
Oxidized low-density lipoprotein (OxLDL) plays a major role in atherosclerosis. We undertook the present study to clarify the relationship between plasma OxLDL and the ischemic volume. We used ELISA to determine plasma OxLDL levels, and performed diffusion- and perfusion-weighted MRI (DWI, PWI) to measure the ischemic volume in 44 ischemic stroke patients. Based on the location of the ischemic lesion, they were divided into three groups: Group I (GI, n = 21) had cortical lesions, Group II (GII, n = 17) had lesions in the basal ganglia or brain stem, and Group III (GIII, n = 6) had massive lesions that involved one entire hemisphere. In GI, but not GII and GIII, plasma OxLDL was significantly higher than in 19 age-matched controls (p < 0.01) and was significantly correlated with the initial ischemic volume visualized on DWI (p = 0.01), PWI (p < 0.01), and the DWI-PWI mismatch (p < 0.05). A persistent increase in plasma OxLDL was associated with enlargement of the ischemic lesion in the early phase after the insult. These findings suggest that elevated plasma OxLDL levels are associated with moderate ischemic damage in patients with cortical lesions (GI), but not those with massive hemispheric lesions (GIII), which may be irreversible. In addition, elevated plasma OxLDL may represent a predictor of enlargement of the ischemic lesion.
Kenji Yagi, Teruyoshi Kageji, Shinji Nagahiro and Y Murayama : Multiple cystic cavernous angiomas associated with hemorrhage, Acta Neurochirurgica, Vol.147, No.2, 201-203, 2005.
(Summary)
A 29-year-old man presented with impaired mental concentration and inability to remember. Magnetic resonance and computed tomography studies revealed multiple calcified cysts. Craniotomy was performed and one of the lesions was resected. The histological diagnosis was cavernous angioma. The first report of multiple cystic cavernous angiomas is reported.
(Keyword)
Adult / Brain / Calcinosis / Central Nervous System Cysts / Cerebral Hemorrhage / Craniotomy / Diagnosis, Differential / Hemangioma, Cavernous, Central Nervous System / Humans / Magnetic Resonance Imaging / Male / Memory Disorders / Neurocysticercosis / Tomography, X-Ray Computed
Junichiro Satomi and Shinji Nagahiro : Hereditary Hemorrhagic Telangiectasia and its Animal Model, Japanese Journal of Neurosurgery, Vol.13, No.12, 830-836, 2004.
(Summary)
Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant vascular dysplasia characterized by dilated vessels and arteriovenous malformations (AVMs). Five to 10% of cerebral AVMs observed in general population are associated with this disease. Two genes, endoglin and activin receptor-like kinase 1, are associated with HHT. To understand the etiology of this disorder, we evaluated the cerebral vasculature of endoglin heterozygous (Eng^<+/->) mice using vascular corrosion cast technique. Eng^<+/-> mice showed significant structural alterations in cerebral blood vessels, indicating that the level of endoglin on endothelium is critical for maintenance of normal vasculature. In this article, we would give an outline of current concepts of HHT and introduce the data obtained from its animal models.
(Keyword)
hereditary hemorrhagic telangiectasia / animal model / malformation vasculature
Teruyoshi Kageji, Shinji Nagahiro, Yoshifumi Mizobuchi, H Toi, Y Nakagawa and H Kumada : Radiation injury of boron neutron capture therapy using mixed epithermal- and themal neutron beams in patients with malignant glioma, Applied Radiation and Isotopes, Vol.61, No.5, 1063-1067, 2004.
(Summary)
The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n = 8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n = 4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n = 6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4+/-4.2 Gy, 15.7+/-1.2 and 13.9+/-3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8+/-1.3 Gy in positive and was 12.6+/-4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8+/-3.8 Gy in positive and was 13.6+/-4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor exists in speech center.
Hao Liu, Masaaki Uno, Keiko T. Kitazato, Atsuhiko Suzue, Shiji Manabe, Hiroyuki Yamasaki, Masayuki Shono and Shinji Nagahiro : Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction., Brain Research, Vol.1025, No.1-2, 43-50, 2004.
(Summary)
Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction.
Mohammad A. Jamous, Koichi Satoh, Junichiro Satomi, Shunji Matsubara, Norio Nakajima, Masaaki Uno and Shinji Nagahiro : Detection of Enlarged Cortical Vein by Magnetic Resonance Imaging Contributes to Early Diagnosis and Better Outcome for Patients With Anterior Cranial Fossa Dural Arteriovenous Fistula, Neurologia Medico-Chirurgica, Vol.44, No.10, 516-521, 2004.
(Summary)
Twelve patients (10 men, 2 women) with anterior cranial fossa dural arteriovenous fistula (AVF) were treated at our institute between January 1976 and March 2002. Intracranial hemorrhage was the presenting symptom in six patients. Magnetic resonance (MR) imaging findings identified abnormal cortical veins as flow voids in four of five patients. Angiography was the basis of the diagnosis in all patients. Surgery was the primary treatment in nine patients. The other three patients refused intervention and managed conservatively. Surgical morbidity was negligible and the treatment outcome was highly dependent on the clinical status at presentation. In contrast to the reported high incidence of intracranial hemorrhage in patients with dural AVF in the anterior cranial fossa, only half of our study population presented with hemorrhage. Enlarged cortical veins in the frontobasal area could be detected as flow voids on MR images. This finding contributed to the early diagnosis and treatment of patients treated at our institution for dural AVF in the anterior cranial fossa, and to the better outcomes we obtained in these patients.
Norio Nakajima, Shinji Nagahiro, Shunji Matsubara and Koichi Satoh : Ruptured de novo thrombotic giant aneurysm induced by ethyl 2-cyanoacrylate, --- Case report ---, Surgical Neurology, Vol.62, No.4, 346-351, 2004.
(Summary)
A very rare case of a ruptured aneurysm induced by ethyl 2-cyanoacrylate is reported. Six years earlier, this 68-year-old woman had undergone microvascular decompression for trigeminal neuralgia during which the left vertebral artery, which compressed the exit zone of the trigeminal nerve, had been detached and fixed to the dura mater of the petrous bone with ethyl 2-cyanoacrylate. Shortly thereafter she underwent microvascular decompression for left-side facial palsy; again ethyl 2-cyanoacrylate was used. Six years later, she suffered a subarachnoid hemorrhage because of rupture of a new aneurysm of the left vertebral artery. She was referred to our hospital where coil embolization was attempted on the day following the insult. However, the left vertebral artery and the aneurysm could not be occluded completely, and she suddenly died 20 days later from rerupture of the aneurysm. This is the first pathologic report of a ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate. We suggest that arterial wall damage by ethyl 2-cyanoacrylate may have contributed to the development of the de novo aneurysm.
Miyuki Kanematsu, Koichi Satoh, Norio Nakajima, Fusamitsu Hamazaki and Shinji Nagahiro : Ruptured aneurysm arising from a basilar artery fenestration and associated with a persistent primitive hypoglossal artery, --- Case report and review of the literature ---, Journal of Neurosurgery, Vol.101, No.3, 532-535, 2004.
(Summary)
A 42-year-old woman experienced the sudden onset of a severe headache. Angiograms demonstrated a persistent primitive hypoglossal artery (PHA) originating from the internal carotid artery at the C-2 vertebral level. In addition, a fenestration at the PHA-basilar artery (BA) junction and an aneurysm at the proximal end of this fenestration were revealed. To perform endovascular embolization of the aneurysm, a microcatheter was introduced into the aneurysm sac via the PHA and two Guglielmi Detachable Coils were placed in the aneurysm. The patient's postoperative course was uneventful, and she was able to resume her normal life. Although many clinical cases have been reported in which a ruptured aneurysm was associated with a PHA or a BA fenestration, as far as the authors know there has been no case in the literature in which a ruptured aneurysm associated with both anomalies and no case in which endovascular embolization was used to treat a ruptured aneurysm associated with a PHA. This rare case is discussed and a review of the relevant literature is presented.
Yoshio Kaji, Masatake Akutagawa, Fumio Shichijo, Yohsuke Kinouchi and Shinji Nagahiro : Development of real-time intra-operative analysis software for brain activity using measured EEG, Transactions of the Japanese Society for Medical and Biological Engineering, Vol.42, No.2, 41-47, 2004.
Kenji Yagi, Koichi Satoh, Junichiro Satomi and Shinji Nagahiro : Primitive Vertebrobasilar System Associated with a Ruptured Aneurysm, American Journal of Neuroradiology, Vol.25, No.5, 781-783, 2004.
(Summary)
Persistent primitive lateral vertebrobasilar (PPLVB) anastomosis is a rare remnant of early fetal development whose occurrence, to our knowledge, has been reported only once. We now report a new variant in which the basilar artery was fed primarily by a PPLVB anastomosis because on one side the vertebrobasilar junction was incompletely developed and on the other it was aplastic. Aneurysmal rupture in this case may be attributable to excessive hemodynamic stress.
Teruyoshi Kageji, Shinji Nagahiro, S Uyama, Yoshifumi Mizobuchi, H Toi, M Nakamura and Y Nakagawa : Histopathological findings in autopsied glioblastoma patients treated by mixed neutron beam BNCT, Journal of Neuro-Oncology, Vol.68, No.1, 25-32, 2004.
(Summary)
Since 1998, we have introduced a mixed epithermal- and thermal neutron beam for boron neutron capture therapy (BNCT) to improve the neutron beam distribution. Sixteen patients with malignant glioma (glioblastoma, n = 14; anaplastic ependymoma, n = 1; PNET, n = 1) were treated by BNCT in Japan. Of these, 9 died; 3 due to cerebrospinal fluid (CSF) dissemination, 1 each of tumor invasion, meningitis, pneumonia, and unknown causes, and 2 patients died of local recurrence or radiation necrosis. The current postmortem study is comprised of 3 patients with glioblastoma who were treated with BNCT employing an epithermal neutron beam and sodium borocaptate (BSH: Na2B12H11SH). None of the patients manifested local regrowth at the primary site. However, in 2 patients there was CSF dissemination; tumor cells were recognized throughout the subarachnoid space. In the other patient, tumor cells had massively invaded the ipsilateral- and contralateral hemisphere and brain stem from the bottom of the tumor cavity via the corpus callosum and cerebral peduncle. Our findings indicate that BNCT can achieve local control of glioblastoma at the primary site. However, to further improve the clinical outcome after BNCT, steps must be taken to prevent CSF dissemination.
Shinji Manabe, Noriyuki Nishimura, Yasuyo Yamamoto, Hiroko Kitamura, Shinya Morimoto, Mayu Imai, Shinji Nagahiro, Susumu Seino and Takuya Sasaki : Identification and characterization of Noc2 as a potential Rab3B effector protein in epithelial cells, Biochemical and Biophysical Research Communications, Vol.316, No.1, 218-225, 2004.
(Summary)
The Rab3 family small G proteins (Rab3A-D) are involved in the regulated secretory pathway of brain and secretory tissues. Among Rab3-interacting proteins, Rabphilin-3, Rim, and Noc2, all of which contain a conserved Rab3-binding domain (RBD3), are generally recognized Rab3 effector proteins in neurons and secretory cells. Although Rab3B was also detected in epithelial cells, its function remained unknown. We isolated cDNA sequences from human epithelial Caco2-cell mRNA by degenerate RT-PCR based on the conserved amino acid sequence of RBD3. Multiple cDNA clones were identified as encoding Noc2. Northern blot analysis revealed that Noc2 mRNA was expressed not only in secretory tissues but also in epithelial tissues and cell lines. A pull-down assay demonstrated that Noc2 bound to Rab3B in a GTP-dependent manner. When Noc2 was co-expressed with the GTP-bound form of Rab3B, it was recruited from the cytosol to perinuclear membranes. Furthermore, overexpression of Noc2 inhibited the cell-surface transport of basolateral vesicular stomatitis virus glycoprotein. These results suggest that Noc2 functions as a potential Rab3B effector protein in epithelial cells.
MA Jamous, Koichi Satoh, Shunji Matsubara, Junichiro Satomi, Norio Nakajima, Masaaki Uno and Shinji Nagahiro : Ischemic basilar artery dissecting aneurysm treated by stenting only case report-, Neurologia Medico-Chirurgica, Vol.44, No.2, 77-81, 2004.
(Summary)
A 45-year-old man presented with enlargement of basilar artery dissecting aneurysm 10 months after suffering brain stem infarction. Combined stenting and placement of Guglielmi detachable coils (GDCs) was planned to obliterate the aneurysm sac. Stent deployment was performed but the procedure was halted to avoid overdosing with contrast material. Cerebral angiography 10 days later showed thrombosis of the aneurysm sac and normalization of the blood flow in the basilar artery. The patient has been followed up for 2 years and showed good clinical and angiographic outcome. Stenting results in obliteration of the aneurysm sac, so a two-stage procedure is recommended.
Kenji Yagi, Teruyoshi Kageji, Shinji Nagahiro and Hidehisa Horiguchi : Growing teratoma syndrome in a patient with a non-germinomatous germ cell tumor in the neurohypophysis--case report., Neurologia Medico-Chirurgica, Vol.44, No.1, 33-37, 2004.
(Summary)
A 16-year-old woman presented with a non-germinomatous germ cell tumor in the neurohypophysis manifesting as progressive visual disturbance, amenorrhea, hydrodipsia, and polyuria. Her serum alpha-fetoprotein and human chorionic gonadotropin levels were elevated. She experienced sudden, rapid visual deterioration and underwent emergency partial tumor removal to decompress the optic nerves. Her vision subsequently improved. Histological examination of the surgical specimens confirmed immature teratoma. She received chemotherapy (ifosphamide 900 mg/m2, cisplatin 20 mg/m2, etoposide 60 mg/m2) for 5 consecutive days. Although the tumor marker levels decreased remarkably, her vision again declined rapidly due to enlargement of the tumor after the first course of chemotherapy. A second radical operation resulted in vision improvement. The tumor specimen showed only mature teratoma elements. This phenomenon, called the growing teratoma syndrome, is very rare in intracranial non-germinomatous germ cell tumors.
Masaaki Uno, Koichi Satoh, Shunji Matsubara, Junichiro Satomi, Norio Nakajima and Shinji Nagahiro : Does multimodality therapy of arteriovenous malformations improve patient outcome?, Neurological Research, Vol.26, No.1, 50-54, 2004.
(Summary)
The strategy for treating arteriovenous malformations (AVMs) has undergone changes and long-term follow-up results remain unclear. To compare the outcomes of different treatment strategies, we divided 112 patients with 113 AVMs into groups with hemorrhagic (n = 71, 62.8%) and nonhemorrhagic (n = 42, 37.2%) AVMs and subdivided these according to the period in which they were treated (before/after 1990). In the more recent period, treatment more frequently involved the use of the gamma-knife and microembolization to the AVM as well as combination therapy. Long-term follow-up showed that the complication rate was lower and the Rankin scale better, in the more recently treated group. Based on our findings we suggest that AVMs should be treated aggressively using a multimodality strategy.
Moyamoya disease (MMD) is a rare entity that results in progressive occlusion of the arteries of the circle of Willis, but the pathogenesis of MMD is unknown. MMD sera (n=32) were tested for anti-endothelial cell antibodies by enzyme-linked immunoassays and flow cytometric analysis. Apoptosis was induced in human umbilical vein endothelial cells by tumor necrosis factor-alpha. We found that a high proportion of MMD sera had anti-endothelial cell antibodies with apoptotic stimuli. Prominent reactivities of MMD sera (72%) with recombinant human alpha-fodrin were observed. Our study demonstrates that MMD sera contain a high incidence of anti-alpha-fodrin autoantibodies, providing new insight into the mechanisms of occlusion of MMD arteries.
Hidehisa Horiguchi, Toshiaki Sano, Zhi-Rong Qian, Mitsuyoshi Hirokawa, Noriko Kagawa, Takehiko Yamaguchi, Takanori Hirose and Shinji Nagahiro : Expression of cell adhesion molecules in chordomas: an immunohistochemical study of 16 cases., Acta Neuropathologica, Vol.107, No.2, 91-96, 2003.
(Summary)
Chordomas are thought to be tumors originating from notochord remnants characterized histologically by cohesive cells with epithelial features and by immunohistochemical expression of epithelial markers. To investigate the expression and distribution of cell adhesion molecules in chordomas, we immunohistochemically studied the expression of representative cell adhesion molecules, E-cadherin, P-cadherin, N-cadherin, beta-catenin, CD44, ICAM-1 (CD54), NCAM (CD56), and VCAM-1 (CD106) in 16 tumors from 16 patients (skull base, n=5; cervical, n=2; sacral, n=9) and 3 cases of fetal notochord. Of 16 tumors, 12 (75.0%) expressed membranous immunoreactivity for NCAM, 10 (62.5%) for VCAM-1, 9 (56.3%) for CD44, 8 (50.0%) for N-cadherin, 6 (37.5%) for beta-catenin, 4 (25%) for ICAM-1, and 1 (6.3%) for P-cadherin. Nuclear staining for E-cadherin was recognized in 11 (68.8%) tumors, and membranous staining for E-cadherin in 3 (18.8%); none of the tumors showed both nuclear and membranous staining. Intranuclear accumulation of beta-catenin was not found in any chordoma. One fetal notochord case showed immunoreactivity for N-cadherin, E-cadherin (some cells showed staining in both cytoplasm and nuclei), CD44 and beta-catenin. These results indicate that chordomas frequently express immunoreactivity for multiple adhesion molecules including VCAM, CD44 and N-cadherin, as well as for NCAM and E-cadherin, as previously reported. These molecules may participate in producing the cellular cohesion evident in tumor morphological structure. Although the precise underlying mechanisms remain to be elucidated, the high frequency of nuclear expression of E-cadherin (11 of 16 cases) may be diagnostically useful.
H. Toi, Masaaki Uno, Masafumi Harada, Kazuhide Yoneda, Naomi Morita, Shunji Matsubara, Koichi Satoh and Shinji Nagahiro : Diagnosis of acute brain-stem infarcts using diffusion-weighed MRI, Neuroradiology, Vol.45, No.6, 352-356, 2003.
(Summary)
There are many reports on acute cerebral infarcts diagnosed by diffusion-weighted MRI (DWI), but few describe brain-stem infarcts diagnosed by this method. Using the apparent diffusion coefficient (ADC), we studied 18 consecutive patients with brain-stem infarcts who underwent DWI during the acute phase. We calculated and compared the ADC ratio (lesion ADC/contralateral ADC) in 10 patients with brain-stem and 23 with supratentorial cortical infarcts examined within 24 h of the onset of stroke. Ischaemic brain-stem lesions were detected in all 15 patients who underwent DWI more than 3 h after the onset, but not in two who had DWI within 3 h of the onset; their ADC ratio was more than 0.95. ADC ratios in patients with brain-stem infarcts decreased as the interval between onset and DWI increased; the decrease was slower than in patients with supratentorial cortical infarcts.
Masaaki Uno, K T Kitazato, Kyoko Nishi, H Itabe and Shinji Nagahiro : Raised plasma oxidised LDL in acute cerebral infarction, Journal of Neurology, Neurosurgery, and Psychiatry, Vol.74, No.3, 312-316, 2003.
(Summary)
The association between oxidised low density lipoprotein (OxLDL) and cerebral infarction is suspected but not established. To determine whether plasma OxLDL is a useful marker for monitoring oxidative stress in stroke patients. Plasma OxLDL concentrations were determined in 56 stroke patients with cerebral infarction (n = 45) or cerebral haemorrhage (n = 11), and in 19 age matched controls, using a novel sandwich enzyme linked immunosorbent assay. Compared with the controls (0.130 (0.007) ng/ micro g LDL, mean (SEM)), OxLDL was significantly raised in patients with cerebral infarction (0.245 (0.022); p < 0.0001) but not in those with haemorrhage (0.179 (0.023)). Patients with cortical ischaemic infarcts (n = 22) had higher OxLDL levels than either the controls (p < 0.0001) or the patients with non-cortical ischaemic infarcts (n = 23) (p < 0.001). Increased OxLDL concentrations in patients with cortical infarcts persisted until the third day after stroke onset. The National Institutes of Health stroke scales in patients with cortical infarction were higher than in those with non-cortical infarction (p < 0.01). There is a significant association between raised plasma OxLDL and acute cerebral infarction, especially cortical infarction. Plasma OxLDL may reflect oxidative stress in stroke patients.
Masaaki Uno, Atsuhiko Suzue, Kyoko Nishi, Koichi Satoh, 新野 清人 and Shinji Nagahiro : 高位頸動脈狭窄病変に対するCEA -後頭動脈と狭窄の高さとの検討-, Surgery for Cerebral Stroke, Vol.31, No.1, 61-66, 2003.
308.
Hiroyuki Yamasaki, Noriko Mizusawa, Shinji Nagahiro, Shozo Yamada, Toshiaki Sano, Mitsuo Itakura and Katsuhiko Yoshimoto : GH-Secreting Pituitary Adenomas Infrequently Contain Inactivating Mutations of PRKAR1A and LOH of 17q23-24., Clinical Endocrinology, Vol.58, No.4, 464-470, 2003.
(Summary)
The molecular events leading to the development of GH-secreting pituitary tumours remain largely unknown. Gsalpha (GNAS1) mutations are found in 27-43% of sporadic GH-secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4-9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH-secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RIalpha regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) on 17q23-24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH-secreting adenomas in about 10%. We re-evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH-secreting adenomas. We analysed exons 8 and 9 of GNAS1 and all exons and the exon-intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH-secreting pituitary adenomas (30 GH-secreting adenomas, two GH and PRL-secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23-24 with four microsatellite markers and intragenic markers of PRKAR1A. Seventeen of 32 (53.1%) tumours showed somatic-activating mutations of GNAS1: 16 (53.3%) of 30 GH-secreting adenomas and one of two GH and PRL-secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23-24 were detected in any of the tumours examined. We reconfirm the important role of activating mutations of GNAS1 in GH-secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis.
Yoshifumi Mizobuchi, Masaaki Uno, 河野 威, 泉谷 智彦, Tetsuya Tamura and Shinji Nagahiro : 腎透析患者の脳出血の治療と予後の検討, Surgery for Cerebral Stroke, Vol.33, 290-294, 2003.
310.
Atsuhiko Suzue, Shinji Nagahiro, Yoshiteru Urai, Osamu Jinnouchi, Tokujiro Kanamori, Kyung Tak Kwak, Hwan Ki Park, Tomoya Kawazoe, Sayaka Ichise, Yuji Shishido, Yumiko Tomita, Takashi Sakai and Kiyoshi Fukui : Astroglial expression of D-amino acid oxidase gene, Flavins and Flavoproteins 2002, 853-856, 2002.
311.
Kyoko Nishi, Hiroyuki Itabe, Masaaki Uno, Keiko T. Kitazato, Hidehisa Horiguchi, Kiyohito Shinno and Shinji Nagahiro : Oxidized LDL in Carotid Plaques and Plasma Associates With Plaque Instability, Arteriosclerosis, Thrombosis, and Vascular Biology, Vol.22, No.10, 1649-1654, 2002.
(Summary)
Oxidation of LDL plays a significant pathogenic role in atherosclerosis. In this study, we attempted to clarify the correlation between the morphology of human atherosclerotic plaques and the oxidized LDL (OxLDL) levels in plasma and carotid plaques. OxLDL levels (ng/microg apolipoprotein B) in plasma and carotid plaques from 44 patients undergoing carotid endarterectomy and OxLDL levels in 17 control plasma and 9 normal intima samples were determined by a sandwich ELISA by using specific antibodies against OxLDL (DLH3) and apolipoprotein B. The plaques were immunohistochemically classified as macrophage (Mphi)-rich and Mphi-poor. In paired samples from individual patients, plaque OxLDL was nearly 70 times higher than plasma OxLDL (mean+/-SEM, 11.9+/-1.7 vs 0.18+/-0.01 ng/microg apoB, P<0.0001). The OxLDL level was significantly higher in Mphi-rich- than Mphi-poor plaques (19.6+/-2.8 vs 5.50+/-0.77 ng/microg apoB, P<0.0001) and corresponded with DLH3 antigen positivity of the plaques. In patients with Mphi-rich plaques, plasma OxLDL was significantly higher than in the controls (0.20+/-0.02 vs 0.13+/-0.01 ng/microg apoB, P=0.02). Our results suggest that LDL undergoes further oxidation in plaques, and that high plasma and plaque levels of OxLDL are correlated with the vulnerability to rupture of atherosclerotic lesions.
Yoshiteru Urai, Atsuhiko Suzue, Osamu Jinnouchi, Kyung Tak Kwak, Shinji Nagahiro and Kiyoshi Fukui : Gene expression of D-amino Acid oxidase in cultured rat astrocytes, Neuroscience Letters, Vol.324, No.2, 101-104, 2002.
(Summary)
Neuromodulative free D-serine is present in mammalian brain, and localized to type-2 astrocytes in culture. D-amino acid oxidase (DAO) is a flavoenzyme that catalyzes D-amino acids. We examined the DAO gene expression in cultured rat astrocytes by reverse transcriptase-polymerase chain reaction. We established a method to prepare highly purified culture of type-1 and type-2 astrocytes from any brain region. This method utilizes combination of cell type specific separation by shaking and subsequent purification by immunopanning or treatment with cytosine arabinoside. We detected higher DAO gene expression in type-1 astrocyte cultures from cerebellum than that from cerebral cortex. In cerebellum, we observed higher DAO expression in type-1 astrocyte cultures than that in type-2. We also revealed that DAO expression in C6, corresponding to type-1 astrocyte, was higher than that in CG-4 derived type-2 astrocytes.
Yoshio Kaji, Hirokazu Nakayama, Masatake Akutagawa, Fumio Shichijo, Qinyu Zhang, Hirofumi Nagashino, Yohsuke Kinouchi and Shinji Nagahiro : Integrated EEG monitoring system of brain functions during operations, International Congress Series, Vol.1232, 289-296, 2002.
(Summary)
In some cases, it is necessary to occlude the blood flow in a part of the brain during the surgical procedure. In such cases, it is very important to monitor brain functions, and to do appropriate treatment in order to minimize the postoperative complication. At present, several kinds of equipment specialized to monitor single modality are being used simultaneously. The aim of this study was to develop an EEG monitoring system which integrates various analyzing methods. It can indicate not only single modality information but also multi modality. In addition, the system has great advantages. It can provide complex diagnostic information by synthesizing the results of the multi modality analysis. The system consists of data acquisition, waveform memory management, and data analysis parts. To add a new analyzing method, a corresponding module was added in this part. This system can be used without difficulty because it is composed of simple modules. The first experimental system with the above architecture was made.
Kyoko Nishi, Masaaki Uno, Kenji Fukuzawa, Hidehisa Horiguchi, Kiyohito Shinno and Shinji Nagahiro : Clinicopathological significance of lipid peroxidation in carotid plaques., Atherosclerosis, Vol.160, No.2, 289-296, 2002.
(Summary)
Several reports have suggested an association between lipid peroxidation and human carotid atherosclerosis, but few reports have demonstrated a link between lipid peroxidation and carotid plaques in humans. In this study, we investigated the relationship between clinical features, histopathological characteristics and lipid peroxidation in patients undergoing carotid endarterectomy (CEA). Forty-one carotid plaques were obtained. A portion of the most severe lesions was subjected to histopathologic examination, and the remainder of the plaques examined for lipid peroxidation. Thiobarbituric acid-reactive substances (TBARS) values were determined as a marker for lipid peroxidation. The lipid-rich core (LC) and macrophage infiltration (Mphi) component as a percentage of total plaque area were measured morphometrically. Based on the results, all plaques were classified into four groups. Group I (GI): LC <10%; Group IIa (GIIa): LC 10-30%, Mphi <5%; Group IIb (GIIb): LC 10-30%, Mphi < or = 5%, and Group III (GIII): LC < or =30%. The plaque TBARS values of GIII were significantly higher than those of GI, GIIa, and GIIb. The TBARS values of GIIb were one-and-a-half times higher than those of GIIa. Our results show that lipid peroxidation in carotid plaques is significantly associated with carotid atherosclerosis, especially plaque instability. These findings provide direct evidence of an association between lipid peroxidation and human atherosclerosis.
Masaaki Uno, Masafumi Harada, Kazuhide Yoneda, Shunji Matsubara, Koichi Satoh and Shinji Nagahiro : Can Diffusion- and Perfusion-weighted Magnetic Resonance Imaging Evaluate the Efficacy of Acute Thrombolysis in Patients with Internal Carotid Artery or Middle Cerebral Artery Occlusion?, Neurosurgery, Vol.50, No.1, 34-35, 2002.
(Summary)
The value of combined diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) for detecting ischemic lesions of patients with acute ischemic injury was analyzed. Combined pre- and posttreatment DWI and PWI studies were used to assess the efficacy of intra-arterial thrombolysis. Intra-arterial thrombolysis was performed within 6 hours of onset in 10 patients who presented with acute middle cerebral artery or internal carotid artery occlusion. DWI and PWI obtained before and after treatment were studied. The final T2-weighted magnetic resonance scans were obtained 1 month after onset. Thrombolysis resulted in recanalization in seven patients. The mismatch ratio percentage ([initial PWI-initial DWI/initial PWI] x 100) and the rescued ratio percentage ([initial PWI-final T2/initial PWI] x 100) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used for neurological assessment of stroke severity at admission and at 1 month after onset. In all patients, the mismatch ratio was greater than 60% (mean +/- standard deviation, 81.7 +/- 16.7%) and was significantly correlated with initial NIHSS score (-0.74; P = 0.03), and the rescued ratio was significantly correlated with the NIHSS score 1 month after the insult (r = -0.83; P = 0.01). In patients who exhibited recanalization of the occluded artery (n = 7), the mean rescued ratio was 89.6 +/- 12.8% (range, 63-100%). In addition, the lesion volume on posttreatment DWI scans and final T2-weighted magnetic resonance images was not enlarged; on posttreatment PWI scans, it was significantly decreased. The NHISS score at 1 month after the insult (2.3 +/- 2.1) was markedly improved as compared with the initial NHISS score (10.7 +/- 3.9). In a small number of patients who presented with internal carotid artery or middle cerebral artery occlusion, the DWI/PWI mismatch ratio correlated with the initial neurological severity. The rescued ratio may be an objective indicator of the efficacy of treatment.
(Keyword)
Diffusion-weighted magnetic resonance imaging / Intra-arterial thrombolysis / Perfusion-weighted magnetic resonance imaging
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11844231
Teruyoshi Kageji, Shinji Nagahiro, S Uyama, Yoshifumi Mizobuchi and T Nakagawa : Clinical review of BNCT using mixed neutron beam in patients with malignant glioma, Research and Development in Neutron Capture Therapy, Medimond Inc., 1085-1091, 2002.
318.
Kenji Yagi, Toshio TUDA, Yoshihito AGAWA and Shinji Nagahiro : Ruptured Aneurysm Associated with Idiopathic Thrombocytopenic Purpura : A Case Report, Surgery for cerebral stroke, Vol.29, No.6, 441-444, 2001.
(Summary)
A 59-year-old woman was admitted for a transient loss of consciousness, vomiting and severe headache. She was alert without neurological deficit then, and brain CT showed SAH (Fisher group 3). Angiography was performed on day 4 and showed left anterior cerebral artery aneurysm. Her previous history was as follows: She had undergone platelet transfusion after a myoma uteri operation when she was 37 years old. At 54 years old, she was diagnosed with idiopathic thrombocytopenic purpura (ITP), and had been receiving prednisolone since then. On admission, her platelet count was low (4.6 × 104/l). We selected delayed surgery, and first -globulin and prednisolone were used to improve the platelet count. The patient developed a transient monoparesis in her right leg about 1 week after admission, but this gradually disappeared. The aneurysm was clipped 2 weeks after admission. The postoperative course was uneventful. We discuss the treatment of ruptured intracranial aneurysm with ITP.
Shunji Matsubara, Koichi Satoh, Junichiro Satomi, Takeshi Miyamoto, Masaaki Uno and Shinji Nagahiro : Guglielmi detachable coil embolization for ruptured lower-midbasilar trunk aneurysms - a report of five cases, Neuroradiology, Vol.43, No.10, 884-890, 2001.
(Summary)
Detachable coil embolization currently plays an essential role for patients with ruptured basilar artery aneurysms, even though it may have an unfavorable outcome and there may be some technical problems of embolization. We describe Guglielmi detachable coil (GDC) embolization for five ruptured lower-mid basilar trunk aneurysms, using a variety of techniques. The patients' ages ranged from 61 to 78 years; Hunt and Kosnik grade was distributed from 2 to 4, and three patients were found to have fenestrations of the lower basilar arteries. All patients underwent aneurysmal embolization at the subacute or chronic stage. The transfemoral route was used in three patients--one of whom, with a wide-necked aneurysm, was treated by the balloon remodeling technique. The transbrachial approach was chosen for the fourth patient, while vertebral artery origin exposure followed by a direct puncture was achieved in the fifth. All patients were assessed with 80-100% aneurysmal obliteration. No patient re-bled after the embolization. Small cerebellar infarction, possibly due to embolism from the obliterated aneurysmal sac, occurred 11 days after the treatment. Of the five patients, four achieved a good recovery, and one became severely disabled. Ruptured basilar trunk aneurysms can be successfully treated with GDC embolization. In addition to the routine transfemoral route, the transbrachial route, direct vertebral artery puncture, and balloon remodeling technique are also useful for the embolization of this location of aneurysm.
Masaaki Uno, Fusamitsu Hamazaki, Takeshi Kohno, Akira Sebe, Hidehisa Horiguchi and Shinji Nagahiro : Combined therapeutic approach of intra-arterial thrombolysis and carotid endarterectomy in selected patients with acute thrombotic carotid occlusion, Journal of Vascular Surgery, Vol.34, No.3, 532-540, 2001.
(Summary)
The feasibility and clinical outcome of intra-arterial thrombolysis followed by carotid endarterectomy (CEA) for acute thrombotic occlusion of the internal carotid artery (ICA) were evaluated. Intra-arterial thrombolysis and CEA were performed in four patients with acute thrombotic ICA occlusion. Computed tomography scans, cerebral angiograms, and the severity of carotid plaques were examined, and the patients' clinical outcome was evaluated. All 4 patients had severe hemiparesis; 3 patients were alert, and 1 patient was lethargic at the time of hospital admission. New lesions were not shown by means of the initial computed tomography scan. ICA occlusion was indicated in all four patients by means of cerebral angiograms; in three patients, middle cerebral artery occlusion was noted. Collateral circulation was manifested in all patients. Partial recanalization of the occluded ICA was obtained in all patients. Two patients with severe residual ICA stenosis underwent an emergency CEA soon after thrombolysis; the other two patients were treated by means of CEA in the subacute or chromic stage. Plaque rupture and intraplaque hemorrhage were seen in all four patients. All four patients recovered completely, and restenosis of the ICA was not shown by means of follow-up angiograms. Intra-arterial thrombolysis followed by CEA may be an effective therapeutic approach for treating acute thrombotic ICA occlusion. The optimal timing of CEA remains controversial.
Masaaki Uno, Masafumi Harada and Shinji Nagahiro : Quantitative evaluation of cerebral metabolites and cerebral blood flow in patients with carotid stenosis, Neurological Research, Vol.23, No.6, 573-580, 2001.
(Summary)
We examined the metabolic and hemodynamic status of patients with severe carotid stenosis and evaluated the effectiveness of carotid endarterectomy (CEA) by comparing pre- and post-operative results of quantitative proton magnetic resonance spectroscopy (1H-MRS) and single-photon emission computed tomography (SPECT). Quantitative 1H-MRS and SPECT were performed in 17 patients with severe carotid stenosis before CEA; in 10 patients the examinations were repeated after CEA. There was a significant correlation between the degree of internal carotid artery (ICA) stenosis and the N-acetyl-aspartate (NAA) concentration, and between CBFand NAA in the basal ganglia. In 10 of the 17 patients (58.8%) we noted a decrease of NAA on 1H-MRS. After CEA in these patients, NAA was significantly increased, and in 7 of 8 patients whose pre-operative SPECT had indicated impairment of cerebral vasoreactivity, it was improved. Quantitative 1H-MRS and CBF measurements can indicate the severity of metabolic and hemodynamic impairment in patients with severe carotid stenosis, and can help to assess the effectiveness of CEA.
(Keyword)
CAROTID ENDARTERECTOMY / CAROTID STENOSIS / PROTON MAGNETIC RESONANCE SPECTROSCOPY / SINGLE PHOTON EMISSION / COMPUTED TOMOGRAPHY
Mohammad Jamous, Koichi Satoh, Teruyoshi Kageji, Junichiro Satomi, Shunji Matsubara, Shinji Nagahiro, Masakazu Hayashi and Shinichi Nakagawa : Anterior Ischemic Optic Neuropathy After Combined Ophthalmic Artery Embolization and Craniofacial Surgery, --- Case Report ---, Neurologia Medico-Chirurgica, Vol.41, No.8, 419-422, 2001.
(Summary)
A 57-year-old man developed visual loss following craniofacial surgery for an inflammatory ethmoidal sinus mass. Surgery was preceded by endovascular occlusion of the ophthalmic artery distal to central retinal artery (CRA). Routine angiography obtained immediately after endovascular ophthalmic artery occlusion showed patency of the CRA. He complained of visual loss one day after craniofacial surgery (2 days after embolization). Repeat emergency angiography confirmed the patent CRA. Ophthalmic examination and fluorescein angiography showed that the visual loss was due to anterior ischemic optic neuropathy (AION). Preservation of the CRA is critical during ophthalmic artery embolization to avoid visual complications. Neurosurgeons should be aware of the possibility of AION as a complication of ophthalmic artery embolization.
Kitade Shuko, Masatake Akutagawa, Qinyu Zhang, Fumio Shichijo, Shinji Nagahiro, Yusuke Morita and Yohsuke Kinouchi : Event related Potentials in a patient with word meaning aphasia with special referencce to topography, 臨床脳波, Vol.43, No.6, 400-404, 2001.
Masaaki Uno, Kyoko Nishi, Kiyohito Shinno and Shinji Nagahiro : Carotid Endarterectomy with External Shunt: A New Device and Indication for Use: Technical Note, Neurosurgery, Vol.48, No.5, 1174-1177, 2001.
(Summary)
We designed a new external shunt system and evaluated its indications and efficacy in patients undergoing carotid endarterectomy (CEA). In 8 of 332 CEA procedures, external shunts were placed between the common carotid artery and the internal carotid artery (ICA). This procedure was implemented for one of two indications: 1) a change in electroencephalographic and/or somatosensory evoked potential readings immediately after ICA occlusion, or 2) elongation of the ICA made safe insertion of an internal shunt impossible. In addition, a shunt was placed between the common carotid artery and the external carotid artery to establish collateral circulation from the external carotid artery to the intracranial circulation, which is essential during ICA occlusion. All external shunts were functional, and electroencephalography and somatosensory evoked potentials demonstrated no significant abnormalities during the CEAs. All patients awoke from surgery without manifestation of new neurological deficits. Our new external shunt device proved safe and efficacious in cases that did not permit the placement of an internal shunt.
Koichi Satoh, Junichiro Satomi, Norio Nakajima, Shunji Matsubara and Shinji Nagahiro : Cerebellar hemorrhage caused by dural arteriovenous fistula: a review of five cases, Journal of Neurosurgery, Vol.94, No.3, 422-426, 2001.
(Summary)
In this study the authors performed a retrospective analysis of five cases in which the patients (three women and two men) were treated for intracranial dural arteriovenous fistulas (AVFs) associated with cerebellar hemorrhage. On the basis of their findings, the authors evaluated the characteristics of this unusual symptom. The dural AVFs were located in the right cavernous sinus in one patient, the left transverse-sigmoid sinus in three patients, and the right superior petrosal sinus (SPS) in one patient. All patients presented with severe headache and/or loss of consciousness. Computerized tomography scans revealed a small cerebellar hemorrhage near the fourth ventricle and hydrocephalus in four cases, and a massive hemispheric cerebellar hemorrhage in the remaining case. The four patients with small hemorrhages underwent ventriculostomy and endovascular treatment; all recovered. The patient suffering from a massive hemorrhage because of a dural AVF in the SPS was treated by suboccipital craniectomy, hematoma evacuation, and removal of the vascular anomaly. This patient remains in a persistent vegetative state. In four cases, results of angiography demonstrated retrograde leptomeningeal venous drainage through the SPS to the anastomotic lateral mesencephalic vein (ALMV) and/or to the vein of the lateral recess of the fourth ventricle (VLR4V). Retrograde leptomeningeal venous drainage to the ALMV and/or VLR4V was responsible for cerebellar hemorrhage in these cases. Thus, it is important to consider dural AVF in cases in which there is even a small hemorrhage near the fourth ventricle accompanied by intraventricular perforation and a decreased level of consciousness.
Kyoko Nishi, 板部 洋之, Masaaki Uno and Shinji Nagahiro : 頚動脈プラークおよび血漿中の酸化LDLの定量とその意義, Therapeutic Research, Vol.22, 293-294, 2001.
327.
Norio Nakajima, Shinji Nagahiro, Toshiaki Sano, Junichiro Satomi and Koichi Satoh : Phenotypic modulation of smooth muscle cells in human cerebral aneurysmal walls, Acta Neuropathologica, Vol.100, No.5, 475-480, 2000.
(Summary)
We used immunohistochemical methods to analyze the phenotypes of smooth muscle cells (SMCs) in human cerebral arteries and aneurysmal walls. Thirty-two aneurysmal walls were studied; 31 aneurysmal walls were resected at operation and 1 aneurysm was obtained at autopsy. Seven control arteries were obtained at autopsy. Semiserial sections were subjected to immunohistochemical staining with antibodies to alpha-smooth muscle actin (alpha-SMA), desmin and smooth muscle myosin heavy chain isoforms: SM1, SM2 and SMemb. In control cerebral arteries, SMCs in the media were strongly immunostained for alpha-SMA, desmin, SM1 and SM2; immunoreactivity for SMemb was faint or weakly positive. SMCs in both non-ruptured and ruptured aneurysmal walls showed no staining for desmin; the expression of alpha-SMA was well preserved. Compared with control cerebral arteries, in 4 of 11 non-ruptured aneurysmal walls, the staining intensity of SMCs for SMemb was clearly increased. In ruptured aneurysmal walls, the expression of SM2 was lower than in control cerebral arteries and non-ruptured aneurysmal walls. Our study suggests that the phenotype of SMCs in aneurysmal walls is different from the contractile type in the media of normal cerebral arteries, at least partially changing to the synthetic type in some non-ruptured aneurysms. SMCs in ruptured aneurysmal walls may have lost both phenotypes before rupture. Phenotypic modulation of SMCs in the aneurysmal walls appears to be related to a remodeling of the aneurysmal wall and to a rupture mechanism.
Masaaki Uno, Shin Ueda, Kiyohito Shinno, Kyoko Nishi, Kazutoshi Nishitani and Shinji Nagahiro : Coronary artery stenosis evaluated by combined carotid and coronary angiography in patients undergoing carotid endarterectomy, Neurologia Medico-Chirurgica, Vol.39, No.8, 567-573, 1999.
(Summary)
The relationship between coronary artery stenosis and the postoperative outcome was investigated in patients who underwent carotid endarterectomy (CEA). The benefit of combined carotid and coronary angiography was also evaluated. Combined carotid and coronary angiography was performed in 72 patients treated with CEA (mean age 64.0 years). Fourteen patients with a history of ischemic heart disease (IHD) had a higher Gensini score for coronary artery stenosis than patients with no history of IHD (37.9 +/- 36.8 vs. 7.9 +/- 12.5, p < 0.0001). However, 39.7% of patients with no history of IHD had a Gensini score exceeding 6. Patients with diabetes mellitus had a significantly higher Gensini score than nondiabetic patients. Eleven patients (15.3%) underwent percutaneous transluminal coronary angioplasty and three (4.2%) underwent coronary artery bypass grafting during the CEA perioperative period. None of the patients who underwent combined angiography showed signs of IHD during or after CEA (mean follow-up period 30 months). Combined angiography was not performed in 189 previous patients. Of these, two died of acute myocardial infarction in the postoperative period, 11 manifested nonfatal IHD, and 18 succumbed to IHD (mean follow-up period 8 years). Although patients with a history of IHD manifested more severe coronary artery stenosis than patients without such a history, the possibility of coronary artery stenosis must be considered in patients with no history of IHD, especially those with diabetes mellitus. Combined carotid and coronary angiography and careful management of coronary artery stenosis can be expected to decrease the mortality and morbidity in patients treated with CEA.
Masaaki Uno, Norio Nakajima, Kyoko Nishi, K Shinno and Shinji Nagahiro : Hyperperfusion syndrome after extracranial-intracranial bypass in a patient with moyamoya disease case report, Neurologia Medico-Chirurgica, Vol.38, No.7, 420-424, 1998.
336.
Koichi Satoh, Junichiro Satomi, Shunji Matsubara and Shinji Nagahiro : Mesurement of volume ratio to predict coil compaction, on aneurysmal embolization, Interventional Neuroradiology, Vol.4, No.Suppl 1, 179-182, 1998.
337.
Kyoko Nishi, Masaaki Uno, S Ueda, K Nishitani, K Shinno, Sh