A 49-year-old male, suddenly suffered from dysarthria and right severe hemiplegia, was transferred to our hospital. Brain magnetic resonance image and angiography showed right pontine fresh infarction and a basilar dolichoectatic thrombosed aneurysm. Echocardiography was normal, so the fresh atherothrombotic brain-stem infarction was caused by the thrombosed aneurysm. Anti-platelet therapy and heparinization were performed after admission. On 20th day after admission, he was discharged with slight hemiplegia, and no increase in the size of the aneurysm was detected. Natural history of dolichoectatic thrombosed aneurysm was not clearly known even now. Our experience showed conservative therapy is effective in the case of atherothrombotic infarction caused by the thrombosed aneurysm. However for the protection from increasing size of the aneurysm, neurosurgical procedure could be needed.

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We report five cases of intracranial hemorrhage related to dabigatran administration. All five cases bled after having changed medicine to dabigatran from Warfarin for non-valvular atrial fibrillation by a family doctor. The blood examination of five patients were almost normal values, and there were no history of previous subcutaneous bleeding or gastrointestinal bleeding. We performed a burr hole operation in one case without prior information of dabigatran administration, because of his stuporous state. Consequently, one patient died and the other went into a vegetative state. Only one patient displayed no significant disability after three months.

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We encountered a patient with internal carotid artery-posterior communicating artery aneurysm rupture which manifested as acute subdural hematomas not accompanied by subarachnoid hemorrhage. A 92-year-old female suddenly developed severe pain in the area from the left cheek to the forehead. At the time of the first visit to our hospital, neurological examination showed mild left blepharoptosis. Head CT and MRI revealed acute subdural hematomas in the posterior cranial fossa and an interhemispheric fissure, but no subarachnoid hemorrhage. Head MRA showed a left internal carotid artery-posterior communicating artery aneurysm, which had not been present two years previously. There was no history of head injury despite repeated history-taking from the patient and her family. Based on the disease history and findings from imaging and neurological examinations, a diagnosis of acute subdural hematomas due to a ruptured cerebral aneurysm was made, and coil embolization for the aneurysm was performed. Acute subdural hematomas not accompanied by subarachnoid hemorrhage, which are due to ruptured cerebral aneurysms, are rarely observed. In patients with acute subdural hematomas, in the absence of a history of injury, head CT, head MRI and evaluation of cerebral blood vessels may be necessary.

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In this review, three recent studies using the National Cerebral and Cardiovascular Center (NCVC) rt-PA registry on arterial occlusion sites and early recanalization in patients with hyperacute ischemic stroke who underwent intravenous thrombolysis are introduced. Koga, et al. reported underlying factors associated with early recanalization failure following thrombolysis. Osaki, et al. reported the significance of the NIH Stroke Scale as simple clinical predictors of stroke outcome during 1-hour infusion of rt-PA. Sakamoto, et al. reported clinical characteristics and outcomes of thrombolyzed patients who showed reverse MRA-DWI mismatch on the initial MR images.

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The qualified treatment of acute stroke strongly depends upon the emergency medical system (EMS), those of the initial actions of patient’s family, activities of emergency medical technician, and the transportation to medical doctors. Tokyo Metropolitan Stroke Association Council has been organized to evaluate the quality of EMS for acute stroke care in Tokyo City and carried out a one week study by using questionnaires given to emergency technicians and to hospitals at 2010 and at 2012. We verified these questionnaires from the point of enlightenment for citizens and of the accuracy for judgment of the emergency technician for acute stroke. The interval between the onset and ambulance call, which is the good indicator of the initial actions of patients’ family was shortened from 42.0 minutes at 2010 to 23.0 minutes at 2012. However, the interval between the ambulance call to the hospital, which is one of the indicator of the quality of EMS became longer from 40.0 minutes to 42.0 minutes. The sensitivity, specificity, and pseudo-negative cases, which are diagnosed as acute stroke by the medical doctors without the evaluation as acute stroke by the emergency technician are reviewed. The sensitivity, and the specificity was 82.4% and 97.9% at 2010, 70.8% and 98.4%, at 2012, respectively. And the cases of pseudo-negative are increased from 64 to 100. For the physicians and nurses working in the emergency room (ER), Japan Triage & Acuity Scale (JTAS) and Immediate Stroke Life Support (ISLS) gradually popularized for the diagnosis of acute stroke.

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The concept of telestroke networks has been proposed to overcome regional disparities in stroke treatment. Such networks do not yet operate in Japan. The geographic information system analysis demonstrated that 6.8–69.3 more patients could be treated by intravenous (IV) tPA annually, when telestroke support was introduced to the existing hospitals. These numbers exceeded the estimated annual increases of 0.8–13.7 more patients if a drip-and-ship telestroke network was introduced into an underserved area outside the 60-minute-driving time area. TPA injection by remote medical support using an interactive videoconferencing system is feasible under the current Japanese infrastructure. Current problems of cost-benefit and cost-effectiveness analysis, guideline and legal issue, establishment of multidisciplinary educational system, reimbursement for services, and licensure and credentialing in Japan were discussed.

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It is well established that antiplatelet therapy is effective for preventing the recurrence of noncardioembolic cerebral infarction. Although aspirin, clopiogrel, and cilostazol are widely used in Japan. The efficacies of these drugs are not sufficient. There is little evidence showing the difference in the efficacy of those drugs. It is common to choose the drug in an individual case by taking into account the characteristics of each drug, such as the side effects and the mechanism of action. Dual antiplatelet therapy (DAPT), i.e. combination of aspirin and clopidogrel, has not been recommended for the secondary prevention of ischemic stroke, because the reduction of cardiovascular events has been offset by the increase of major bleeding. However, it was shown that DAPT is effective for the patients of acute ischemic stroke in a recent study. Based on this evidence, DAPT might be both effective and safe if it was started within 24 hours from onset and lasted only for 21 days. On the other hand, novel antiplatelet drugs have been developed. New ADP receptor antagonists, which have more rapid and strong antiplatelet action with less individual differences than clopidogrel, have been approved in USA and Europe for patients with acute coronary syndrome, and phase III trials are in progress in Japan. It would be more important to select the appropriate drugs and their doses in individual patients, if the option of antiplatelet agents will increase in the future. Thus, more detailed risk assessment and information about pharmacongenomics would become required.

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Various modalities of regenerative approaches have been tried to promote neural replacement in the injured brain, such as transplantation of bone marrow stromal cells and iPS cells. On the other hand, intrinsic approach using endogenous neural stem cells has also been investigated. Irrespective of approaches employed, maturation and survival of these progenitors or transplanted cells would depend on surrounding environment within the lesion. Our groups has conducted basic experiments to utilized endogenous neural stem cells to replace lost neurons in a model of transient global ischemia, where selective neuronal loss occurs in vulnerable regions. We found that infusion of growth factors (EGF, FDG-2) for a short period of time significantly promoted the regenerative process in hippocampal CA1 and dorsolateral striatum after rat forebrain ischemia, the most vulnerable regions. In both models, morphologically mature regenerated neurons extended axons, made functional synaptic contact, and contributed to improvement in cognitive and motor performances. In addition, a combination of phasic treatment, initially by growth factors followed by Notch inhibitor (γ secretase inhibitor), significantly promoted differentiation into neuronal pathway, and significantly increased the number of mature neurons in the hippocampal CA1 sector. Though in which kind of lesions neuronal regenerative approach, using intrinsic mechanism can be applied, is not clear at present. Elucidation of inhibitory mechanisms in various lesions might lead to a novel regenerative therapeutic strategy.

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The most important advantage of novel oral anticoagulant therapy when compared to warfarin, is the low rate of intracranial hemorrhage. Intracranial hemorrhage includes hemorrhagic stroke and subdural hematoma in the same population, and only the occurrence of subdural hematoma showed dose dependency. Among the Asian population, the rate of ischemic stroke was higher than that of the non-Asian population, and the rate of intracranial hemorrhage was the same, therefore, the dosage of NOAC should not be reduced in Asian patients. Another sub-analysis showed that even in the elderly population, the dosage should not be reduced if renal function remains within a normal range. Although the investigation regarding an antidote for NOACs is moving forward, we must pay special attention to the patients’ renal function not only in the initial phase but also periodically during the later phase as well.

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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.

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