Japanese Journal of Stroke
Online ISSN : 1883-1923
Print ISSN : 0912-0726
ISSN-L : 0912-0726
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Volume 32, Issue 6
Displaying 1-44 of 44 articles from this issue
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Proceedings of the 35th Annual Meeting of the Japan Stroke Society
Presidential Address
Review
  • My stroke study
    Akira Ogawa
    2010 Volume 32 Issue 6 Pages 515-524
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.515
    JOURNAL FREE ACCESS
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    In my opinion, clinical doctors should find research themes through daily contact with their patients, and findings should be applied for the benefits of patients and their treatment. Results of medical research as a life science may greatly contribute to humanity in the near future, even if they have little to contribute at present. Clinical doctors have many research areas to consider, and they have to make enormous efforts to explore areas that only clinical doctors can think of. Today, the world of medicine and medical care is advancing so fast that the common beliefs in the present medical world turn into the uncommon in ten years’ time. In order to keep up with this change and advancement, clinical doctors need research mind.
    Although the Japanese medical care system for stroke patients is ranked highly in the world, most of this system is supported only by the voluntary, devotional, and personal work of stroke specialists. We have to recognize our goals in order for the medical care system for stroke patients to function healthily as a social system. At the same time, we have to direct a united effort towards leading the world of medicine and medical care for the better.
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Symposium 1
Review
  • Cell transplantation therapy for the stroke: Role of transplanted stem cell in brain repair
    Nobutaka Horie, Izumi Nagata, Tonya Bliss, Gary K. Steinberg
    2010 Volume 32 Issue 6 Pages 525-531
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.525
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    Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. In this study, we test the hypothesis that grafted human neural stem/progenitor cells enhance the endogenous repair that occurs after stroke. Moreover, we summarize the results from present pre-clinical and clinical studies and focus on the potential mechanisms (angiogenesis, BBB integrity, axonal sprouting, dendritic branching, and inflammation) in functional recovery after cell transplantation.
    We found that transplanted cells affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier (BBB) integrity and suppression of inflammation was followed by a delayed spatio-temporal regulated increase in neovascularization. These events coincided with a bi-modal pattern of functional recovery: an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multi-modal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component. We also demonstrated that transplanted cells enhance axonal sprouting and dendritic branching of host neurons after stroke, and that these plasticity changes correlated with cell-induced recovery.
    The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.
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  • Progress and perspective of bone marrow stromal cell transplantation for ischemic stroke
    Satoshi Kuroda, Hideo Shichinohe, Taku Sugiyama, Masaki Ito, Masato Ka ...
    2010 Volume 32 Issue 6 Pages 532-537
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.532
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  • Production and degeneration of extracellular matrix regulates cerebral aneurysm growth and are potential targets for aneurysm treatment
    Tomohiro Aoki, Masaki Nishimura, Hiroharu Kataoka, Ryota Ishibashi, Ry ...
    2010 Volume 32 Issue 6 Pages 538-543
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.538
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    Cerebral aneurysm (CA) is a main cause of a lethal subarachnoid hemorrhage. Given the high incidence of CA in general population, the mechanisms of CA formation should be unlabelled and novel medical therapy for CA before rupture should be developed. The typical pathological feature of CA walls is the decrease of extracellular matrix (ECM). Decreased ECM results in the weakness of CA walls leading the enlargement and rupture of CA. In this article, we have reviewed the recent findings about the mechanisms of decreased ECM in CA walls mainly revealed by experiments using rodent CA models. ECM is the dynamic structure with the continuous synthesis and degeneration of matrix protein. In CA walls, the induced expressions of proteinases by chronic inflammation in arterial bifurcation are present and actively participated in the pathogenesis of CA. Further the synthesis of collagen is suppressed in CA wall through inflammatory stimulus in arterial walls. These results combined together indicate that both decreased synthesis and increased degeneration of ECM by chronic inflammation in CA walls contributes to CA formation. Further these results demonstrate the therapeutic potential of anti-inflammatory drugs for CA.
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  • Proteomic analysis in ischemic stroke
    Masahiro Kamouchi, Tetsuro Ago, Tetsu Isomura, Keiichiro Kanatani, Hid ...
    2010 Volume 32 Issue 6 Pages 544-551
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.544
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    Ischemic stroke is the most common cause of disability and death. Optimal therapy should be performed in patients with ischemic stroke as early as possible to improve their functional outcome and prognosis. Biomarkers for ischemic stroke would be helpful for early diagnosis and optimized therapy. However, heterogeneity of the mechanisms and clinical background in individual patients hampers the identification of biomarkers for ischemic stroke. To date no confident biomarker has been available for ischemic stroke in clinical setting. Recent progress in proteomic analysis enables us to detect minimal change in the plasma proteins. We designed REBIOS (Research for Biomarkers in Ischemic Stroke) to discover novel biomarkers in acute ischemic stroke. In this study, ischemic stroke patients who had been hospitalized within 24 hours of onset were enrolled and time-course changes in plasma proteins were investigated using proteomic approach for 3 months. Proteins in a patient with each stroke subtype were compared with those in age- and sex-matched control. Top-down and bottom-up analyses have identified multiple protein candidates, which could be useful for diagnosis of ischemic stroke with high sensitivity and specificity. A variety of proteins associated with angiogenesis, neurogenesis, and inflammation showed dynamic changes from hyperacute to chronic stage. Identification of yet unknown proteins may be helpful to better understand the mechanisms for repair and regeneration after ischemic insults and will contribute to the discovery of novel drugs. We review current status and future perspective of proteomic analysis in ischemic stroke.
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  • Oxidative stress induced by cerebral ischemia-reperfusion and neuroprotection: Potentiality of pH-responsive radical-containing nanoparticle (RNP)
    Aiki Marushima, Kensuke Suzuki, Yukio Nagasaki, Toru Yoshitomi, Kazuko ...
    2010 Volume 32 Issue 6 Pages 552-558
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.552
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    Free radicals produced by cerebral ischemia and reperfusion can extend the infarct area by the damage of ischemic penumbra, which is known as ischemia-reperfusion injury. Nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) have unique anti-oxidant abilities to scavenge free radicals. However, short in vivo half-life and toxicity have limited their clinical application. In this report, the property of radical-containing nanoparticle (RNP), which was developed to overcome the limitations of nitroxyl radical, was introduced, and the molecular mechanism of it’s accumulation to ischemic brain and the scavenging effect of free radicals were demonstrated.
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  • Effects of transcranial near-infrared laser irradiation on cerebral blood flow in mice
    Hiroshi Nawashiro, Youichi Uozumi, Shunichi Sato, Satoko Kawauchi, Hir ...
    2010 Volume 32 Issue 6 Pages 559-562
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.559
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    Objectives: It has been reported that near-infrared (NIR) laser irradiation is effective in cerebral ischemia. We examined the effect of 808 nm laser diode irradiation on CBF in mice. The potential of NIR laser irradiation in the treatment of cerebral ischemia was also investigated.
    Methods: Male C57BL/6J mice were used. An 808 nm CW diode laser was applied to the hemisphere transcranially. CBF was measured with a non-contact laser Doppler blood perfusion imager. We measured directly nitric oxide in the brain tissue during NIR laser irradiation. To confirm the effect of pretreatment by NIR laser irradiation, we conducted the 1.6 W/cm2 NIR laser irradiation to the hemisphere transcranially for 30 minutes before bilateral common carotid artery occlusion (BCCAO). The control mice were also subjected to BCCAO without pretreatment by NIR laser irradiation.
    Results: Transcranial NIR laser irradiation increased local CBF by 30% compared to control value in mice. NIR laser irradiation also provoked a significant increase in cerebral NO concentration. Pretreatment by NIR laser irradiation improved residual CBF following bilateral carotid occlusion in mice.
    Conclusions: Our data suggest that targeted increase of CBF is available by NIR laser irradiation and it is concerned in NOS activity and NO concentration. Besides, NIR laser irradiation may have a protective effect for transient ischemia.
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Short Report
  • Electrical stimulation on cerebral infarct
    Takao Yasuhara, Masahiro Kameda, Tanefumi Baba, Takamasa Morimoto, Tom ...
    2010 Volume 32 Issue 6 Pages 563-565
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.563
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    Improvement of motor functions of stroke patients receiving electrical stimulation has been reported while its mechanism unknown. We explored the therapeutic effects with mechanisms of electrical stimulation on MCAO model of rats. In the study using MCAO model of rats in the acute stage, infarct volumes reduced significantly with behavioral ameliorations. Anti-apoptotic, angiogenic and anti-inflammatory effects were involved in neuroprotective effects of electrical stimulation. In the study of the chronic stage, therapeutic effects were confirmed with enhanced migration of newly developed neurons to the penumbra. Electrical stimulation may be a strong therapeutic strategy for stroke, although further studies are required.
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Symposium 2
Original
  • Clinical characteristics and outcome of acute ischemic stroke; the Fukuoka Stroke Registry
    Takanari Kitazono, Masahiro Kamouchi, Hiroshi Nakane, Tsuyoshi Omae, H ...
    2010 Volume 32 Issue 6 Pages 566-571
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.566
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    Fukuoka Stroke Registry (FSR) is a multicenter epidemiological and observational study of acute stroke involved seven stroke centers in Fukuoka Prefecture. FSR is consisted of two database systems, i.e. prospective and retrospective databases. Prospective database started June 1, 2007 recruited consecutive patients with acute stroke within seven days from the onset attending one of the centers. 88% of potentially eligible patients consented to participate in this registry. Prospective database collected data on patient demographics and medical history, and prehospital, emergency, and in-hospital interventions and outcomes. Moreover, both plasma and genome were sampled for the future analysis and log-term prognosis 3 months, 6 months, 1 year, 2 years after onset was collected by telephone or mail. The surveillance data were collected by 99.6% of the participating patients. From June 1, 2007 to February 28, 2010, 3,133 patients were enrolled in the prospective registry. Data of 5,515 patients who admitted to the participating medical centers from June 1, 1999 to May 31, 2010, were collected in the retrospective registry. From the 8,648 patients, 2,441 consecutive patients with brain infarction with complete information were selected for the analysis. The mean age of the patients was 71.4 years and 60% were male. In terms of stroke subtypes, 2,441 patients were brain infarction and the frequencies of lacunar infarction, atherothrombotic infarction, cardioembolic stroke, and undetermined type of brain infarction were 26%, 23%, 22%, and 29%, respectively. FSR is a useful system to evaluate clinical characteristics and clinical outcome of the patients with acute ischemic stroke.
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  • An observational study of stroke patients on the prognosis and causes of death in 5 years: Comparison of the results in Tochigi prefecture with the reports in the U.S.A.
    Akira Imai, Hiromi Suzuki, Teruki Watanabe, Noriko Umeyama, Mitsuo Tsu ...
    2010 Volume 32 Issue 6 Pages 572-578
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.572
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    Background and Purpose: In order to clarify the natural history of stroke patients, we observed the long-term prognosis of stroke patients and causes of death after stroke, and compared the results with the reports by American Heart Association.
    Methods: 5,081 patients with acute stroke were registered from April 1998 through March 1999 in Tochigi prefecture and followed up for 5 years and 9 months. Survival rates after stroke were estimated by Kaplan-Meier survival curves.
    Results: The 5-year survival rate after stroke was 62.3%. The 5-year survival rates after each stroke type were 54.9% for subarachnoid hemorrhage (SAH), 57.9% for cerebral hemorrhage (CH) and 62.8% for cerebral infarction (CI), respectively. Major causes of death after hemorrhagic stroke (SAH, CH) were stroke, heart diseases and malignant neoplasms. Major causes of death after ischemic stroke (CI) were stroke, heart diseases, and respiratory diseases. Main cause of death within 30 days after hemorrhagic stroke (SAH, CH) was stroke itself. Pneumonia was the remarkable cause of death for the patients over 75 years old with CI. Estimated fatality rates in 5 years after stroke in Tochigi prefecture were 38.5% in male and 36.7% in female. The rates were lower than those reported in the U.S.A., 47% in male and 51% in female.
    Conclusions: We think that not only the initial treatment for acute stroke is important, but also the management of pneumonia in the chronic stage of CI is important to improve the prognosis of stroke.
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Symposium 3
Review
  • Certified nurse of stroke rehabilitation nursing education and role
    Ayako Tamura
    2010 Volume 32 Issue 6 Pages 579-581
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.579
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    2010, in Japan first, “certified nurse of stroke rehabilitation nursing,” 79 person authorized.
    This paper was introduced certified nurse of stroke rehabilitation nursing, birth and education.
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  • Expectation to the stroke rehabilitation nurse
    Yoichiro Hashimoto
    2010 Volume 32 Issue 6 Pages 582-588
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.582
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    The nurses in my hospital made the brain infarction degree of rest expansion manual which took care of brain infarction patients in 1995. The purposes of the manual were the prevention of disuse syndrome, the early mobilization and rehabilitation, the pain reduction of patients, the presentation of the future treatment policy for patient and family, and an aim for patient oneself, the shortening in length of hospital stay. In 1996, stroke neurologist in Saiseikai Kumamoto Hospital converted it into the critical pathway for the brain infarction. The effectiveness of stroke unit was shown for the same period. Stroke unit and the essence of critical pathway are team medical care.
    We must construct stroke network by function differentiation and referral system. We take much difficulty to referral system, but can solve many problems of stroke. Liaison critical pathway for stroke appeared as one means of the referral system. Illness becomes the object for the acute period, obstacle for the convalescence period, and life for the maintenance period. Two pillars of continuity of the treatment and the continuity of the rehabilitation are necessary for the stroke referral system. The continuation of the nursing is included in the both. A stroke rehabilitation nursing authorization nurse system was started in 2009. I expect that the stroke rehabilitation nurses carry out the role of the leadership in stroke medical examination and treatment.
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Symposium 4
Original
  • The current situation and issues of the surgical treatments result for brain hemorrhage
    Koichi Okamura, Ryuichi Yamaguchi, Hidenori Seyama, Keisuke Maruyama, ...
    2010 Volume 32 Issue 6 Pages 589-594
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.589
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    The aim of this study to evaluate treatment results for brain hemorrhage at Kyorin University Faculty of Medicine. We treated consecutive 152 cases of brain hemorrhage. We studied to examine their treatment contents and mRS (modified Rankin scale) at the time of their discharge.
    The surgeries were performed for 53 cases. Outcome of cerebellar and subcortical hemorrhage was relatively satisfactory compared to other bleeding sites and mRS: 0–2 was recognized in about 40% of the cases. In contrast, outcome of brain-stem hemorrhage was poor, and it caused 30% of overall mortality.
    There has been no specific evidence regarding surgical intervention for brain hemorrhage. As for putaminal hemorrhage which is likely to develop pyramidal tract disorder, the functional prognosis tends to deteriorate easily compared to cerebellar and subcortical hemorrhage, and it was considered to be the limit for judging prognostic evaluation based on functional assessment. Decisions for surgical indication for severe cases and significance of lifesaving effects include important life ethical issues, which are to be worked on in order to establish decision making methods which can be effective with limited time and manpower and to combine them with the development and application of regenerative medicine in future.
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  • Endoscopic hematoma evacuation for the hypertensive putaminal hemorrhage
    Takuji Yamamoto, Takanori Esaki, Yasuaki Nakao, Kentaro Mori
    2010 Volume 32 Issue 6 Pages 595-601
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.595
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    Method: We reviewed 351 clinical charts which were treated in Juntendo University Shizuoka Hospital diagnosed as hypertensive putaminal hemorrhage. Of all patients, 124 patients were enrolled in this study. The functional prognosis at discharge from our hospital was evaluated in three categories divided by the hematoma volume and in three different treatment methods as follows; conservative therapy (CT), endoscopic hematoma evacuation (ES), microscopic hematoma evacuation via craniectomy (MI).
    Results: In the category which the hematoma volume was between 30 ml and 50 ml, modified Rankin Scale (m-RS) of ES was significantly better than CT and MI. The mortality rate of ES was the lowest in the both category [(20 to 40 ml: CT: 16.7% and ES: 5.1%), (40 to 80 ml: ES: 5.9%, MI: 9.1%)], though there was no significant difference in m-RS.
    Discussion: The prognosis was improved by the endoscopic procedure in moderate severity that the hematoma volume was 30 ml to 50 ml, however the prognosis of patient with mild and severe putaminal hemorrhage, was not statistically improved by endoscopic procedure. In the patient with 50 ml or more hematoma, the stage of treatment may promptly be able to be shifted to the recovery rehabilitation by the less invasive technique such as endoscopic hematoma evacuation.
    Conclusion: In the patient with moderate severity which may correspond to the severity of putaminal hemorrhage with 30 ml to 50 ml hematoma, the endoscopic hematoma evacuation would be the effective for the improvement of the functional prognosis.
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  • Examination of acute treatment strategies in 314 patients with putaminal hemorrhage from the view point of functional prognosis in Kaifukuki rehabilitation wards
    Masaharu Sakoh, Yuji Ohmura, Ryousuke Fujii, Hirotsugu Horimi, Ken Ish ...
    2010 Volume 32 Issue 6 Pages 602-610
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.602
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    Purpose: We examined the influence of acute treatment strategies for putaminal hemorrhage from the view point of the functional prognosis in Kaifukuki rehabilitaiton wards.
    Methods: Subjects were 314 patients with putaminal hemorrhage for inpatient rehabilitation in our hospital. For all patients, Functional Independence Measure (FIM), Barthel Index (BI), Indepenndence of Gait (IOG) was measured on admission and discharge, respectively. We examined the functional prognosis, according to method of treatment, age, volume of hematoma, CT classification, side of damage, sex, and hospitalization waiting period.
    Results: A significant difference was admitted with FIM, BI, and IOG in the age, the volume of hematoma, the hospitalization waiting period, and the CT classification (p<0.05). The functional prognosis was excellent in the conservative treatment than in the surgical treatment. The hospitalization waiting period was significantly a long term in the surgical treatment (p<0.05). In the analysis where the age is arranged the volume of hematoma, the surgical treatment was more excellent than the conservative treatment, in the patients less than 70 years old and the volume of hematoma with 60 ml or more.
    Conclusion: The functional prognosis of putaminal hemorrhage was excellent in the conservative treatment, but the stereotactic hematoma evacuation is recommended to the limited case as a surgical treatment. Early rehabilitation is a pressing need for the improvement of the fuctional prognosis. Especially, it is indispensable to shorten the hospitalization waiting period in the surgical treatment.
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Symposium 5
Short Report
  • A comparison study of MPRAGE and histopathology of carotid plaques
    Tomohito Hishikawa, Koji Iihara, Naoaki Yamada, Hatsue Ueda, Isao Date
    2010 Volume 32 Issue 6 Pages 611-613
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.611
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    Taking the close association between MRI assessment of carotid plaques using MPRAGE sequence with symptomatology, we sought to evaluate the correlation between MPRAGE signal intensity and histopathology. MPRAGE signal intensity was significantly correlated with the area of necrotic core (NC) and the degree of intraplaque hemorrahage (IPH). The plaques with MPRAGE high signal, which was defined as more than 200% of that of adjacent muscle, revealed significantly larger NC and more severe IPH than those with low signal. MPRAGE is useful in detecting pathological vulnerable plaques and the intervention of MPRAGE in the management of carotid artery stenosis is feasible.
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Symposium 6
Review
  • Pathophysiology of vascular cognitive impairment
    Masafumi Ihara, Yoko Okamoto, Ryosuke Takahashi, Hidekazu Tomimoto
    2010 Volume 32 Issue 6 Pages 614-620
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.614
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    Insufficiencies of blood supply will more or less lead to brain dysfunction. Cognitive impairment caused by such cerebrovascular insufficiency was called vascular cognitive impairment (VCI), a clinical syndrome composed of a markedly heterogeneous group of diseases rather than a unique pathological process. It includes large vessel disease with strategic single or multiple strokes and small vessel disease with progressive damage to the basal ganglia and/or the white matter. VCI was previously believed to be distinct from Alzheimer’s disease (AD) resulting from a neurodegenerative process. However, such simple dichotomy needs to be reconsidered in light of the shared features between AD and VCI: these two disorders increase in prevalence with age, frequently occur concomitantly, and considerably overlaps in their symptomatology, pathophysiology, and comorbidity. So-called ‘mixed’ brain pathologies, mainly comprising of AD pathology and cerebral infarctions, are reported to account for most dementia cases in community-dwelling elderly people. Consistent with this notion, the contributors to attributable risks at death for dementia include small vessel disease and multiple vascular pathologies, which are no less than those of the main pathological hallmarks of AD, neocortical neuritic plaques and neurofibrillary tangles. Importantly, the multifactorial aspects of cognitive impairment have been incorporated in the dynamic polygon hypothesis, which takes into account the contributions of strokes of all sizes and white matter hyperintensities in parallel to those of plaques and tangles. In terms of the treatment of dementia, it is undoubtedly important to control vascular risk factors for the prevention of VCI. However, even in patients who have AD without cerebrovascular disease, treatment of vascular risk factors is associated with a slower decline in the Mini-Mental State Examination score. Therefore, physicians should always bear in mind that vascular risk factors need to be controlled to achieve a reduction in the risk of dementia, even if the dementia is caused by AD.
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Original
  • Cognitive dysfunction and cerebral blood flow in patients with stenosis of internal carotid artery using the Frontal assessment battery (FAB)
    Aiko Osawa, Shinichiro Maeshima, Fumitaka Yamane, Hiroshi Matsuda, Sho ...
    2010 Volume 32 Issue 6 Pages 621-627
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.621
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    Stenosis of internal carotid artery is one of the risk factor of vascular dementia. However, because most patients can live alone, it is not so easy to find out the cognitive impairment for such patients. We therefore performed simple neuropsychological tests to evaluate overall cognitive function and to clarify the relationships between cognitive function, especially frontal lobe function, and the white matter lesions or regional cerebral blood flow (rCBF) for patients who have symptomatic carotid artery stenosis. Frontal assessment battery (FAB) was effective to detect bilateral severe stenosis. FAB had significant relations to the severity of periventricular hyperintensity, but not the of carotid artery stenosis. Additionally, there were significant correlation between FAB and rCBF of bilateral frontal lobe, thalamus and wide area of right hemisphere. These results investigated that chronic hypoperfusion of wide area may be play a role in the deterioration of cognitive, especially frontal lobe, dysfunction in the patients with stenosis of internal carotid artery.
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Review
  • Hemodynamic correlates of vascular risk factors in vascular dementia and Alzheimer’s disease
    Takashi Yamazaki, Daiki Takano, Tetsuya Maeda, Ken Nagata
    2010 Volume 32 Issue 6 Pages 628-633
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.628
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    Many evidences suggested a coexistence of vascular lesions in Alzheimer’s disease (AD), although there had been a dichotomy between AD and vascular dementia (VaD) in the clinical diagnosis of dementias. To clarify the hemodynamic correlates of the vascular risk factors in AD and VaD patients, we investigated the relationship between the cerebral blood flow (CBF) images provided by SPECT and vascular risk factors. The present study was based on 157 patients with probable VaD and 59 patients with probable AD. On the CBF images, 122 (77.7%) of 157 VaD patients showed a hypoperfusion in the frontal lobe and 114 patients (72.6%) showed a hypoperfusion in the parieto-temporal region. All AD patients underwent laboratory testings, neuropsychological evaluation, MRI and 99mTc ECD SPECT. Based on the existence of the white matter hyperintensity (WMH) and/or subcortical infarction on MRI, all patients were classified into 2 categories: those without WMH (Group A) and those with WMH (Group B). MMSE scores negatively correlated with patients’ age, BNP, and HOMA-R. Statistical parametric mapping (SPM) revealed a significant hypoperfusion in the frontal lobe in Group A as compared with Group B. Those with greater BNP showed a significant hypoperfusion in the anterior cingulate gyri and superior frontal gyri as compared with those with smaller BNP. As compared with those with smaller HOMA-R, those with greater HOMA-R showed a significant hypoperfusion in the anterior cingulate gyri and frontal lobe. The frontal hypoperfusion which was associated with vascular risk factors might modify the hemodynamic pathophysiology in AD patients.
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Original
  • Rehabilitation management for stroke patients with cognitive impairment: Influences of malnutrition on cognitive and motor impairment in stroke rehabilitation
    Eriko Yokoyama, Akiko Nakano
    2010 Volume 32 Issue 6 Pages 634-640
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.634
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    Background and Purpose: Malnutrition is a common complication of strokes associated with poor clinical outcomes in rehabilitation. The purpose of this study was to clarify influences of malnutrition on cognitive and motor function following stroke in the chronic phase.
    Methods: The present study included 381 stroke patients who underwent nutritional and functional assessment at admission and on discharge after a mean 107-days of rehabilitation. Functional measures were motor age (MA), Barthel index (BI), Functional Independence Measure (FIM), Hasegawa scale (HDS), Standard Language Test for Aphasia (SLTA) and Behavioral Inattention Test (BIT). Nutritional states were evaluated by using body mass index (BMI), serum albumin concentration, body weight loss, and lymphocyte count. Malnutrition was defined if the patient had one or more abnormal nutritional parameters. All the patients had rehabilitation for cognitive and motor impairment during hospitalization.
    Results: Malnutrition was observed in 263 (69%) of 381 patients. Malnourished patients showed the lower BMI and serum albumin, and the poorer cognitive and motor function in MA, BI, FIM, HDS, SLTA and BIT. BMI and serum albumin showed significant association with cognitive and motor functional measures, including MA, BI, FIM, HDS, SLTA and BIT.
    Conclusion: Stroke patients with malnutrition had a greater risk of poor cognitive and motor functional outcome in the chronic rehabilitation phase. Appropriate nutritional support may have favorable improvement on clinical outcome.
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Symposium 7
Original
  • Quality-assurance monitoring in thrombolytic therapy: Concept and results of Kawasaki Stroke Network
    Yasuhiro Hasegawa, Taku Shigeno, Ryousei Iwai, Kazunari Suzuki, Hiroyu ...
    2010 Volume 32 Issue 6 Pages 641-646
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.641
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    Background and Purpose: We established triage and bypass transportation systems for thrombolytic therapy in the community and repeatedly monitored their quality by clinical indicators.
    Methods: Modified Cincinnati Prehospital Stroke Scale, named Maria Prehospital Stroke Scale (MPSS), and a decision tree linked with the MPSS score were developed for stroke bypass-transportation in Kawasaki City. Quality-assurance monitoring was repeatedly performed every six months.
    Results: A total of 174 patients were transferred by the stroke bypass-transportation system. 145 patients (83.3%) were transferred to the stroke center in Kawasaki city, but 21 (12.1%) were transferred to the hospitals in the neighboring cities. Thrombolytic therapy was performed in 36 patients (23.8%). Mean onset-to-injection time was shortened by 10 minutes and the rate of modified Rankin scale score less than 2 was 42.9%.
    Conclusion: Quality-assurance monitoring for thrombolytic therapy in the community is feasible and useful for improving quality of care without regional difference.
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Review
  • Comprehensive referral system for stroke and high-risk patients: Shizuoka Stroke Network
    Masahiro Kobari, Noboru Imai, Yasunori Fukuchi, Shinichiro Oka, Tatsuo ...
    2010 Volume 32 Issue 6 Pages 647-653
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.647
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    Since late 2006, we have managed a local medical network, or referral system, for stroke and high-risk patients in Shizuoka City. Six general hospitals, which treat 88% of all emergency patients in the area, four rehabilitation facilities, and approximately 220 practitioners have joined the network.
    The Shizuoka Stroke Network consists of two connected networks: firstly, a network for patients who develop stroke; and secondly, a network for high-risk patients. The former intends to realize smooth referral of stroke patients to rehabilitation facilities, and then to practitioners. The later is for repeated, scheduled referrals of high-risk patients to general hospitals from practitioners. At present, 1626 patients (1021 for the stroke patient network and 605 for the high-risk patient network) are registered to this network.
    The Shizuoka Stroke Network has contributed to swift referral of patients among different medical facilities. It has also fermented a sense of security among ailing stroke patients. Meanwhile, increased clerical paper work related to the network is a burden to doctors and office workers.
    To complete this comprehensive stroke network in the Shizuoka area, further cooperation with emergency medical services and chronic care facilities is required.
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Original
  • The development of digitalized version of stroke liaison critical pathway
    Tadashi Terasaki, Yoshufumi Hirata, Yoichiro Hashimoto, Makio Yamaga, ...
    2010 Volume 32 Issue 6 Pages 654-659
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.654
    JOURNAL FREE ACCESS
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    We have operated paper-based stroke liaison critical pathway in Kumamoto area since 2007, though felt difficulties in restoring, keeping quality of and analyzing the data. Therefore, we developed digitalized version of the pathway with FileMaker Pro® in the same form of paper-based pathway, which would be low-cost, simple and adoptable for all participating facilities.
    After entering data, we printed the pathways and used them as paper-based pathways. Entered digital data were restored in every hospital, collected, interlinked and analyzed afterward. We distributed this digital version in Oct. 2009 and promoted gradually in coexistence with the paper-based pathway. The data of 1152 patients were collected by Sept. 2010.
    Mutual data movement would be possible with other database including stroke data bank and rehabilitation patients bank.
    Further consideration is necessary about handling of individual informations.
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  • Standardization of critical pathways for regional stroke care networks in Kanagawa
    Toshinori Yamashita, Satoshi Nishimura, Koji Yorizumi, Koichi Suzuki, ...
    2010 Volume 32 Issue 6 Pages 660-667
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.660
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    The authors have tried to form the system of the common critical pathways for regional stroke care networks in Kanagawa prefecture. That contributes to improve the system of transferring stroke patients from acute hospitals to rehabilitation ones and the system of performing seamless care going over regional community areas.
    We have held the Meeting of Western Kanagawa Stroke Care Network consisted of ten acute hospitals and seven rehabilitation hospitals. 625 critical pathways were used in this network between April 2008 and February 2010. The using rate of our critical pathways was 44%.
    The Kanagawa prefectural common critical pathway has just been propelled in the Committee of Kanagawa Seamless Stroke Care Networks. Thirteen regional stroke care network groups in all areas of Kanagawa prefecture have been joinning in this committee. The using rate of this critical pathway in 760 cases admitted to our institute from these network groups was 41.7%.
    For the future we would establish a stroke care network from acute hospitals to maintenance hospitals and community support clinics. Our goal should be not a cooperation of hospitals but a regional alliance, and a local conclusion of stroke care.
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Symposium 8
Review
  • MR perfusion imaging for stroke
    Kei Yamada, Kentaro Akazawa, Tsunehiko Nishimura, Katsuyoshi Mineura, ...
    2010 Volume 32 Issue 6 Pages 668-674
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.668
    JOURNAL FREE ACCESS
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    Perfusion weighted imaging (PWI) had been introduced as a clinical tool in the mid 90 s and had quickly gained popularity, mainly in advanced medical facilities. The idea known as diffusion-perfusion mismatch (DPM) was expected to reflect regions that are at risk for infarction but may be still salvageable through thrombolysis. Although this concept seemed to be a simple and plausible one, the negative results from large-scale clinical trials have shock the reliability of this scheme. Research results of the tissue fate prediction have also shown that these may be challenging through the use of PWI. Thus, the value of PWI has been always questioned in the past few years. If, however, one limits its use to assessing the presence of ischemia, then it becomes apparent that this is indeed a powerful diagnostic tool. We thus believe that, despite the negative results from recent studies, the PWI will continue to be part of the clinical routine.
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Original
  • Basic concept and clinical application of continuous arterial labeling (CASL) as a means of CBF measurement without contrast media: Reliability and limitation
    Hirohiko Kimura, Hidehiko Okazawa, Yoshikazu Arai, Kenichirou Kikuta
    2010 Volume 32 Issue 6 Pages 675-679
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.675
    JOURNAL FREE ACCESS
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    Arterial spin labeling (ASL) provides a quantitative measurement of cerebral blood flow, which uses the state of magnetization in blood water as an intrinsic tracer. The continuous ASL (CASL) based on 3DFSE sequence can be recently implemented on 3T MR system, which can produce the better SNR and wider coverage than before. So far as the clinical application, this method has been applied to patients with acute infarction, chronic occlusive cerebrovascular disease and Alzheimer disease etc. In the a case of moyamoya disease with delayed collateral blood flow, ASL fails to visualizes true perfusion without valid parameter setting. The caution is needed, when one would apply it to the cases with elongated transit time in occlusive cerebrovascular disease. However, post operative repeated ASL perfusion images was successfully performed in a case with MCA occlusion after STA-MCA anastmosis, which suggests this method could become routine adjunct for the assessment of perfusion in daily practice.
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Symposium 9
Case Study
  • The enlightenment of action on stroke patients to the local populace and the pre-hospital emergency medical system
    Akifumi Suzuki, Taizen Nakase, Shotaro Yoshioka, Masahiro Sasaki
    2010 Volume 32 Issue 6 Pages 680-683
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.680
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    After the approval of intravenous administration of rt-PA for patients of acute cerebral infarction, the emergency medical system has been improved and the enlightenment of action on stroke patients to the local populace has been carried out. However, the number of patients treated by rt-PA has not increased markedly. It is considered that the effect of enlightenment of action on stroke patients to the local populace is not enough. The limit is considered in the effect of the enlightening activity of the lecture form. Then, the enlightening activity by the event form that those who came were able to learn by themselves according to their interest was done. In the event, the signs of stroke and the method of emergency call were presented by the short play. The evaluation of the effect of enlightenment is difficult, but we will continue the enlightening activity by the event form.
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  • Stroke team leadership over education for medical students and stroke care workers in the community
    Masaki Saitoh, Yasuyuki Yonemasu, Akira Takahashi, Hidehito Yoshida, Y ...
    2010 Volume 32 Issue 6 Pages 684-688
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.684
    JOURNAL FREE ACCESS
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    With leadership of Stroke Team, we have performed various forms of education for health care professionals and medical practitioners related to stroke, that is to say Stroke Care Workers. Our work includes 1) on-site seminars at hospitals in the community, 2) open lectures for citizens to provide information of risks and effects of stroke, 3) an analysis of contents of national examinations for all qualifications relating to stroke care and treatment, 4 and 5) off the job trainings on PCEC/PSLS and ISLS for paramedics in the community, 6) stroke seminars for clinical residents in the hospital, 7) introducing a practical examination on the NIHSS as a part of the graduation test, 8) t-PA and NIHSS lectures for medical students provided by Stroke Team, 9) stroke seminars for health caregivers in the community, and 10) developing teaching materials for stroke education.
    Since the stroke medicine has reached a highly advanced stage, we think following four points will be important for future medicine of stroke, 1) providing education with a great emphasis on appropriate quality, needless to say on quantity, 2) widening education to provide not only for the staff inside hospitals, but also for health care practitioners including caregivers working in the community, 3) developing common materials of stroke education for Stroke Care Workers to eliminate the knowledge gap, and 4) cultivating people s understanding of stroke because of its significant impact on our society, and developing public awareness of importance of the education of stroke medicine.
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  • Motivation change of medical students after stroke seminar by stroke team
    Masaki Saitoh, Yasuyuki Yonemasu, Wari Yamamoto, Takahiro Anegawa, Kun ...
    2010 Volume 32 Issue 6 Pages 689-693
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.689
    JOURNAL FREE ACCESS
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    We held stroke seminar and practical skill guidance of NIH stroke scale for medical students at 5th and 6th grader. The contents were a slide session and a video message from nurse, patients, and their family to medical students in primary stroke center and practical skills session facilitated by stroke team (doctor, nurse, speech therapist). As a result of questionnaire that reached after a class, we understood this. After the attendance of this class, interest to the stroke of the medical student became strong, and, the students who wanted not to be concerned with stroke medicine decreased. The medical student expected professionalism, abundant experience and knowledge, a viewpoint except the doctor from a nurse and a speech therapist participating in a class as a facilitator.
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Joint Symposium 1 (the Japan Stroke Society and Japanese Society on Surgery for Cerebral Stroke)
Review
  • The current situation and prospects of revascularization therapy for acute ischemic stroke in the world and Japan
    Kazuo Minematsu
    2010 Volume 32 Issue 6 Pages 694-696
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.694
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    The author contributed to accomplish a phase III clinical trial named Japan Alteplase Clinical Trial (J-ACT), that examined the efficacy and safety of intravenous (i.v.) thrombolytic therapy with a recombinant tissue-type plasminogen activator (rt-PA), alteplase, and to issue a Japanese guideline of i.v. alteplase therapy. In this joint symposium, the author reviewed results of clinical studies performed in Japan after the approval of alteplase in 2005, which included the SUMO study, the NCVC rt-PA Registry, the SAMURAI Register, a clinical trial of J-ACT II, and the nation-wide post-marketing registry of J-MARS. For these years, many clinical studies have been performed in the North America and Europe to prolong the therapeutic time window from the initial 3 hours to the 4.5 hours by using alteplase and to the 9 hours with a new rt-PA, desmoteplase, and to develop intravascular devices such as Merci and Penumbra, sonothrombolysis and hybrid revascularization therapy. These new therapeutic strategies are also going to be tested clinically in Japan.
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Case Study
  • Thrombolysis with 0.6 mg/kg intravenous alteplase for acute stroke in routine clinical practice: the outline of Japan post-Marketing Alteplase Registry Study (J-MARS)
    Jyoji Nakagawara, Kazuo Minematsu, Yasushi Okada, Norio Tanahashi, Shi ...
    2010 Volume 32 Issue 6 Pages 697-703
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.697
    JOURNAL FREE ACCESS
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    The aim of the Japan post-Marketing Registration Study (J-MARS) 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 finally enrolled in J-MARS, an open-label, non-randomized, observational study, from October 2005 to October 2007. Primary outcome measures were symptomatic intracranial hemorrhage (sICH) (a deterioration in NIHSS score ≥4 from baseline, or the ICH leading to death) and favorable outcome (mRS 0–1) at 3 months after stroke onset. The proportion of patients with sICH in 7492 patients (safety analysis) was 3.5% within 36 hours and 4.4% at 3 months. The overall mortality rate was 13.1% and the proportion of patients with fatal sICH was 0.9%. The outcomes at 3 months were available for 4944 patients and the proportion of favorable outcome (efficacy analysis) was 33.1%, and the proportion of mRS 6 was 17%. The subgroup analysis in 3576 patients between 18 and 80 years, with a baseline NIHSS score <25 demonstrated that favorable outcome at 3 months was 39.0%. 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.
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Joint Symposium 2 (the Japan Stroke Society and Japanese Society on Surgery for Cerebral Stroke)
Case Study
  • Introduction: New concepts of management of TIA as a medical emergency
    Yasushi Okada, Mayumi Mori, Masahiro Yasaka, Shinji Nagata
    2010 Volume 32 Issue 6 Pages 704-709
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.704
    JOURNAL FREE ACCESS
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    In patients with transient ischemic attacks (TIA), immediate consultation to a specialized institution, examination and treatment have made the marked reduction of subsequent stroke. Early risk stratification by ABCD2 score has been useful to predict the risk of subsequent ischemic stroke early after TIA. High quality examinations, involving carotid ultrasonography, MRI diffusion weighted imaging, and MR angiography are also valuable for management of TIA. To prevent recurrent stroke from the high risk TIA, life-style, and comprehensive management of hypertension, diabetes mellitus, dyslipidemia, heart disease and peripheral arterial disease, as well as anti-thrombotic therapy and surgical intervention are quite important.
    We need to spread the awareness that TIA is viewed as acute cerebrovascular syndrome (ACVS) and its importance as the last chance before completed irreversible stroke. Large Japanese multi-center cooperative study is ongoing to evaluate the short-term and long-term vascular event rates as well as risk factor profiles, predictors of vascular events, and current medical practice. Nationwide educational campaigns should be done, focusing on the awareness of high risk TIA using ABCD2 score and reducing stroke recurrence.
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Original
Review
Original
  • Antithrombotic treatments for transient ischemic attack
    Haruhiko Hoshino
    2010 Volume 32 Issue 6 Pages 725-730
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.725
    JOURNAL FREE ACCESS
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    Background and Purpose: Immediate antithrombotic treatment is necessary for patients experiencing a transient ischemic attack (TIA) to prevent stroke. The actual treatment of TIA was examined and compared with the recommendations of the Japanese Guidelines for the Management of Stroke 2009.
    Methods: Seventy-one patients admitted because of a TIA were evaluated.
    Results: Twenty (28.2%) of the TIA patients were atherothrombotic (TIA-AT), 12 (16.9%) were cardioembolic (TIA-CE), and 39 (54.9%) were categorized as others (TIA-Others). During admission, intravenous anticoagulants with antiplatelets were administered in 27.3% of the TIA-AT patients, and intravenous antiplatelets were administered in 45.0%. Intravenous anticoagulants with antiplatelets were administered in 16.7% of the TIA-Others patients, and intravenous antiplatelets were administered in 31.0%. Intravenous anticoagulants were administered in 58.3% of the TIA-CE patients. At the time of discharge, 30.0% of the TIA-AT patients were prescribed dual antiplatelets.
    Conclusions: Many patients admitted with TIA were treated with intravenous antithrombotic agents that are not mentioned in the Guidelines. Hospital admission is useful for evaluating the pathophysiology promptly and immediately starting antithrombotic treatments in TIA patients.
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Short Report
  • International multicenter cooperative observational study
    Shinichiro Uchiyama, George Nakagawara, Ken Nagata, Kazuo Minematsu, H ...
    2010 Volume 32 Issue 6 Pages 731-734
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.731
    JOURNAL FREE ACCESS
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    TIA is a medical emergency. Because, the risk of stroke early after TIA is very high. It has been reported that immediate evaluation and management of TIA substantially reduced the risk of subsequent stroke. Therefore, TIA patients should be evaluated and treated as soon as possible in a TIA clinic during 24 hours for 365 days. Based on these backgrounds, we conducted an international multicenter cooperative, investigator-driven, web-based observational study (TIAregistry.org). Five thousand patients with TIA or minor stroke (Rankin 0 or 1) within 7 days after the onset will be recruited and followed up for 5 years. The primary endpoint is non-fatal stroke, non-fatal MI or vascular death. The secondary endpoint is any vascular event or endovascular intervention. The investigational endpoints include quality of treatments, clinical manifestations, etiologies, times from first medical attention, and risk prediction scores. The background demographics include neurological symptoms, brain MRI and MRA, carotid ultrasonography, echo cardiography, blood pressure, CBC, lipids, and glucose. More than 5,000 patients will be recruited until July, 2011. Six Japanese stroke centers join the registry to recruit the target number of 300 patients. This registry may provide important information on evaluation and management of TIA as a medical emergency.
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Joint Symposium (the Japan Stroke Society and the Japanese Society on Thrombosis and Hemostasis)
Review
  • Warfarin resistance in Japanese population
    Takehiko Nagao
    2010 Volume 32 Issue 6 Pages 735-739
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.735
    JOURNAL FREE ACCESS
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    In the clinical setting, many doctors are confused that warfarin’s efficacy is affected by a variety of external factors, including the food and drugs patients ingest. In addition, it was recently discovered that certain genetic factors related to warfarin metabolism play important roles in determining warfarin’s efficacy. Two enzymes, CYP2C9 and VKOR are known to be major factors which affect the vitamin K pathway. In the Japanese population, gene polymorphism of both enzymes is different compared to western populations. As a result many Japanese tend to have a higher sensitivity to warfarin. Therefore, for Japanese patients, maintenance therapy with warfarin should be more carefully monitored.
    We also warned that the quality of the prothrombin time reagent affects the accuracy of PT-INR monitoring.
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  • Clopidogrel resistance
    Kazuo Umemura
    2010 Volume 32 Issue 6 Pages 740-745
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.740
    JOURNAL FREE ACCESS
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    Clopidogrel is an inactive prodrug requiring several biotransformation steps, mediated mainly by cytochrome P-450 isoforms (CYP), in order to generate an active metabolite (AM) that binds irreversibly to the platelet ADP receptor P2Y12. It was reported that polymorphism of CYP2C19 affects the pharmacokinetics of the AM and the pharmacodynamic response to clopidogrel. The prevalence of CYP2C19 poor metabolizers (PMs) is much greater (18% to 23%) in Asian people than that (3% to 5%) in Caucasian American or European populations. Therefore, in this study, in Japanese healthy subjects, we investigated whether the polymorphism of CYP2C19 would affect the formation of the AM and antiplatelet effects to the AM. 300 mg clopidogrel was orally given to 47 subjects in single dose study. The mean AUC and Cmax of the AM differed significantly (P<0.05) between the extensive metabolizers (EMs) and the intermediate metabolizers, as well as EMs and the PMs. Moreover, the pharmacokinetic parameters of the AM correlated well with the inhibition of ADP-induced platelet aggregation. These findings suggest that the CYP2C19 pharmacogenomic status is a determinant for the formation of the AM in Japanese healthy subjects.
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The 4th Ischemic Stroke t-PA Conference
Review
Original
  • Intravenous rt-PA therapy for acute ischemic stroke in our hospital
    Tomoko Takahashi, Hideaki Kato, Hideki Ohyama, Hiroshi Niizuma
    2010 Volume 32 Issue 6 Pages 751-755
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.751
    JOURNAL FREE ACCESS
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    We experienced 633 patients of cerebral infarction from July 2007 through July 2009. Sixty (9.6%) cases of them were admitted within 2 hours from onset. Eleven (1.7%) of 60 patients were treated with rt-PA intravenously. Ten of 11 patients had improvement of NIHSS score 24 hours after rt-PA injection. Total outcome was favorable although one patient had intracerebral hemorrhage. Seven patients treated without rt-PA because of lower NIHSS score than 4 had been deteriorated later. Rt-PA therapy for minor stroke patients can be considerable.
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Review
  • Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry: General results and subanalyses
    Kazunori Toyoda, Masatoshi Koga, Yoshiaki Shiokawa, Jyoji Nakagawara, ...
    2010 Volume 32 Issue 6 Pages 756-761
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.756
    JOURNAL FREE ACCESS
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    Stroke Acute Management with Urgent Risk-factor Assessment and Improvement [SAMURAI] rt-PA Registry is a multicenter retrospective observational study from 10 Japanese stroke centers. A total of 600 patients (223 women, 72±12 years old) treated with intravenous alteplase (0.6 mg/kg) were studied. Symptomatic intracerebral hemorrhage within 36 hours with ≥4 point-increase from the baseline NIH Stroke Scale score developed in 8 patients (1.3%, 95% CI 0.7–2.6%). At 3 months, 199 patients (33.2%, 29.5–37.0%) had a modified Rankin Scale (mRS) score ≤1. Analysis of 399 patients with a premorbid mRS score ≤1 who met the criteria of the European license (≤80 years old, an initial NIHSS score ≤24, etc.) showed that 40.6% (35.9–45.5%) had a 3-month mRS ≤1. In the subanalyses from this registry, early ischemic change on diffusion-weighted imaging assessed by the Alberta Stroke Programme Early CT Score, as well as reduced estimated glomerular filtration rate, was associated with early intracerebral hemorrhage and 3-month outcomes of patients.
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Case Study
  • Results from the post marketing alteplase registration study: Reconsideration from the view point of Japanese guidelines for intravenous application of rt-PA (alteplase) 2005
    Yasushi Okada, Takenori Yamaguchi
    2010 Volume 32 Issue 6 Pages 762-769
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.762
    JOURNAL FREE ACCESS
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    From the viewpoint of the Japanese guidelines 2005 for intravenous application of rt-PA (alteplase), the results of post-marketing registration studies on intravenous application of rt-PA in Japan was evaluated for two years. The evaluation was conducted with regard to items such as contraindications, careful administrations, post-administration control (restriction of thrombolytic therapy). The number of contraindication patients in rt-PA administration was 481 (6.4%), 19.5% of which had fatal outcome. The death rate in patients complicated with low platelet counts (less than 100,000/mm3), which fits a case of contraindication, was significantly high. Symptomatic intracranial bleeding was frequently observed in patients with high pre-therapy systolic blood pressure. As for careful administrations, poor outcome was observed in elderly patients, patients in a coma or with high-NIHSS, or those who had pre-treatment thrombolytic therapy. The results indicated the validity of the guidelines 2005. No significant increase in symptomatic intracranial bleeding or poor outcome was observed in concurrently administrated patients, although concurrent thrombolytic therapy within 24 hours of rt-PA therapy is regarded as prohibited. The package insert does not prohibit the concurrent thrombolytic therapy within 24 hours of rt-PA therapy, which should be carefully reconsidered.
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Short Report
Original
  • J-ACT II: Differences in rate of valid recanalization and of a favorable outcome by site of MCA occlusion
    Teruyuki Hirano
    2010 Volume 32 Issue 6 Pages 773-777
    Published: November 26, 2010
    Released on J-STAGE: December 03, 2010
    DOIhttps://doi.org/10.3995/jstroke.32.773
    JOURNAL FREE ACCESS
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    Background and purpose: To elucidate whether the effects of alteplase differ with occlusion site of the middle cerebral artery (MCA).
    Methods: An exploratory analysis was made of 57 patients enrolled on the Japan Alteplase Clinical Trial II (J-ACT II). The residual vessel length (mm), determined on pretreatment MRA, was used to reflect the occluded site. The proportions of patients with valid recanalization (modified Mori grade 2–3) at 6 and 24 hours, and a favorable outcome (modified Rankin scale 0–1 at 3 months) were compared between the groups dichotomized according to their lengths of residual vessel. Multiple logistic regression models were generated to elucidate the predictors of valid recanalization and a favorable outcome.
    Results: ROC analysis revealed that 5 mm was the practical cutoff length for the dichotomization. In patients with M1 length <5 mm (n=12), the frequencies of valid recanalization at 6/24 hours (16.6%/25.0%) were significantly low compared with those (62.2%/82.2%) of 45 patients with a residual M1 length of ≥5 mm and M2 occlusions (p=0.008 for 6 hours, p<0.001 for 24 hours). The proportion of a favorable outcome was also small in patients with M1 length <5 mm (8.3%), as compared to the others (57.8%, p=0.004). In logistic regression models, the site of MCA occlusion (<5 mm) was the significant predictor of valid recanalization at 6/24 hours and of a favorable outcome.
    Conclusions: In patients with acute MCA occlusion, residual vessel length <5 mm on MRA can identify poor responders.
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