We have developed computer based stroke database for acute stroke patients in 1999–2001 by the fund of Ministry of Health, Labour and Welfare Organization. We started registration of stroke since 2001 and accumulated more than 50,000 stroke cases until 2009. The Japanese Stroke Databank was established in Japanese Stroke Association since 2002. This databank is using global standard for evaluation of stroke diagnosis (NINDS 3), severity of stroke (NIHSS, JSS) and prognosis (modified Rankin Scale). Now, 173 institutes joined Japanese Stroke Databank.
Cardiogenic embolism occupied 19.2% among all stroke subtypes. This rate is close to lacunar infarction (22.7%). Because, non-valvular atrial fibrillation is increased with aging in Japan. Hisayama study also revealed cardiogenic embolism markedly increased during 30 years.
We have made historical control data for clinical study of t-PA therapy.
Stroke databank also showed that pre-onset using of antithrombotic agent in the patients of hypertensive hemorrhage was a significant risk for poor prognosis.
This stroke database is useful to made clinical study like as J-STARS.
We are now developing direct transfer system from electric medical record to stroke database. We also developed bidirectional data transfer system between acute hospital and rehabilitation hospital/prehospital care team.

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At the 5th Presidential Lecture of the Japan Stroke Society (JSS), I summarized the path I have walked for the past 6 years as President, and commented on the prospects and remaining issues for the Society.
Among the 20 manifesto points that I proposed 5 years ago and the additional 10 points that I added 2–3 years ago, about 70% have been successfully completed.
However, I regret that I could not complete the followings items:
1. the question of publicity for stroke specialists
2. the establishment of stroke basic law
3. to make a part of the JSS homepages available in English
4. incomplete establishment of the Brain Attack campaign for the public, patients and rescue personnel
5. greater accumulation of clinical data for Japanese patients
6. internationalization of the Japan Stroke Society.
Therefore, I would like to ask my successors to complete my leftovers, and in particular, to enthusiastically maintain the Society’s support for public services, such as education about stroke for the public, rescue personnel, comedical workers and students, not only in Japan, but also in other countries, particularly Asian developing countries.
I am looking forward to watching the continuing progress and development of the Japan Stroke Society.

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Gene transfer technique may be applicable to the treatment of serious types of stroke. Recently the concept of neurovascular protection is proposed as an important strategy for brain infarction. We have examined usefulness of gene transfer approach for neurovascular protection in brain ischemia. Using a focal brain ischemia model of spontaneously hypertensive rats, post-ischemic gene transfer of soluble Flt-1 markedly inhibited the ischemia-induced disruption of blood brain barrier permeability and attenuated ischemic damages. Gene transfer of dominant negative MCP-1 or interleukin-10 significantly inhibited infiltration of inflammatory cells and reduced infarct size. Using gene-deletion technique, we have found inflammatory interleukins mediated by infiltrated macrophages and γδT cells played pivotal roles in the evolution of brain infarction. Gene transfer of midkine, a novel growth factor, reduced apoptotic cell death and infarct volume with enhancement of neuronal precursor cell migration. Gene transfer technique appears to have a potential for neurovascular protection, and these molecular approaches may lead to the development of novel therapeutics for brain infarction.

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Intravenous administration of recombinant tissue plasminogen activator (rt-PA) remains the effective way to treat for acute ischemic stroke. Recently, sonothrombolysis by using both rt-PA and transcranial Doppler (TCD) which are able to observe the microembolic signals and the recanalization of cerebral arterial occlusion is a new and an additional treatment approach. Experimental studies have shown that thrombolysis with rt-PA can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Based on these findings, the CLOTBUST trial revealed that 83% of patients achieved any recanalization (46% complete, 27% partial) with rt-PA+TCD vs 50% (17% complete, 33% partial) with rt-PA alone within 2 hours of treatment (P<0.001). Several clinical studies of sonothrombolysis showed that any diagnostic ultrasound monitoring can at least double the chance of complete arterial recanalization at no increase in the incidence of symptomatic intracerebral hemorrhage. Addition of gaseous perflutren-lipid microspheres to rt-PA and ultrasound monitoring can further facilitate early flow improvement, with a 50% rate of early, complete recanalization in a recent study. Catheter-based ultrasound delivery to arterial thrombi is the subject of ongoing clinical trials. Long-term outcome remains a major concern in the further development of sonothrombolysis.

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New therapeutic strategies are explored for patients suffering from cerebral infarct. Gene therapy is one of the hopeful strategies and we have studied ex vivo gene therapy for stroke using animal models of cerebral infarct over a decade. In this review, we describe encapsulated cell transplantation using neurotrophic factor-producing cells and neurotrophic factor-producing neural stem/progenitor cells for cerebral infarct model of animals. Furthermore, the perspectives of gene therapy for cerebral infarct are reviewed.

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Cerebral aneurysm (CA) can cause subarachnoid hemorrhage which is a devastating illness with a high mortality and morbidity. Given its high prevalence and susceptibility to subarachnoid hemorrhage, treatment of CA is socially important. However, there is currently no medical treatment of CA because detailed mechanisms of CA formation remain unclear. We recently found that NF-kappa B (NF-κB) was a mediator of inflammation in CA walls. NF-κB was activated during CA formation mainly in the endothelial cells and macrophages which were main inflammatory cells in CA walls. Activated NF-κB regulated the MCP-1 expression resulting in the accumulation of macrophage in CA walls. Next, we inhibited NF-κB activity by two different strategies, p50 deficient mice and decoy oligodeoxyneucleotides. Both inhibitions resulted in the effective suppression of CA formation through the decreased inflammation suggesting that NF-κB played the crucial role on CA formation as a mediator of inflammation. Statin (HMG-CoA reductase inhibitor) is widely used as a powerful cholesterol lowering drug. Statin also has an anti-NF-κB activity known as the pleiotrophic effect. Statin orally given to rat CA model effectively inhibited the CA growth and thinning of media. These results suggest that statin is a leading candidate of drugs to treat human CA.

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Motor cortex stimulation (MCS) delivered concurrently with rehabilitation therapy may enhance motor recovery following stroke. We investigated the effects of MCS on the recovery from upper extremity paresis in patients with chronic stroke. In 12 patients who had moderate arm and finger paresis at more than 4 months after stroke, an electrode was placed through a small craniotomy on the epidural space of the motor cortex that was identified using functional MRI. MCS during occupational therapy for one hour was performed 3 times a day for at least 4 weeks. The mean scores for Fugl-Meyer assessments of the arm improved, from 37 preoperatively to 46 postoperatively. The mean grip strength improved from 3.25 to 9.0kg. All patients appeared satisfactory in their results because they recognized an improvement of arm function. Although the mechanism of the beneficial effects of MCS on recovery after stroke has not been well known, the neuroplasticity might play a important role. In a few cases of the present series, it was observed that the hand motor cortex area detected on functional MRI had been enlarged after MCS therapy. MCS could become a novel neurosurgical treatment modality for the chronic post-stroke weakness.

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The Adult Health Study (AHS) was established in 1950 to observe the late effects of radiation exposure among atomic bomb survivors in Hiroshima and Nagasaki. The original AHS cohort consisted of about 20,000 atomic bomb survivors selected from residents in Hiroshima and Nagasaki using the 1950 national census. Since 1958, the AHS subjects have been followed through biennial health examinations. Data accumulated from this 50-year long-term follow-up study have been utilized for a wide range of research activities, from radiation effects research to clinical epidemiological research including studies on stroke, dementia, and other outcomes.
Dementia study in the AHS demonstrated that prevalence of Alzheimer’s disease was higher than vascular dementia among women. In a recent stroke study, lifetime risk for stroke was firstly estimated among Japanese. We also demonstrated that blood pressure in middle life predicted lifetime risk of stroke. No effects of A-bomb radiation on dementia were observed, and analysis of its relationship with stroke continues.
This long-term, large-scale follow-up study continues to provide significant epidemiological findings for disease prevention.

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We performed sub-analyses on the data from the MEGA (Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese), a large randomized controlled trial of lipid-lowering treatment with pravastatin for primary prevention of cardiovascular events in 7,832 patients with mild to moderate hypercholesterolemia. The main analysis of the MEGA Study showed that reducing low-density lipoprotein cholesterol level by 18% with pravastatin was associated with a significant 30% reduction in coronary heart disease and 35% reduction in stroke incidence at 5 years of follow-up. In a sub-analysis on 5,356 women, women aged 60 years or more who were treated with diet plus pravastatin had a markedly higher risk reduction by 64% for stroke than did women treated with diet alone. The results of sub-analyses on both 2,110 diabetic and 3,277 hypertensive patients indicated that risk reduction with pravastatin was more substantial in cerebral infarction than in coronary heart disease (57% versus 32% and 46% versus 29%, respectively). These results indicated that pravastatin treatment can prevent stroke in post menopausal women as well as men, and do so more than coronary heart disease in diabetic and hypertensive Japanese patients with hypercholesterolemia. The Proportion of Treatment Effect (PTE) analysis suggests that such effects are related to pleiotropic effects beyond cholesterol-lowering effect more in stroke prevention than in prevention of coronary heart disease.

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Stroke patients often suffer higher brain dysfunction that impairs their quality of life. However, there is little evidence regarding effective medicines to address impaired higher brain function. We examined the effects of treatment with choto-san, an herbal medicine; ropinirole, an anti-Parkinson drug; and cilostazol, an anti-platelet agent on higher brain dysfunction after stroke. After administration of choto-san, patients had significantly improved Mini Mental State Examination and verbal fluency test scores. In event-related brain potentials, P3 latency was significantly shortened, and the amplitude was significantly larger, after choto-san administration. Patients receiving ropinirole therapy showed improved apathy scale and Frontal Assessment Battery scores, used to assess frontal lobe function in patients with frontal lobe ischemic stroke. Compared with the aspirin treatment group, the cilostazol treatment group exhibited significantly improved apathy scale scores. This study suggests that some medicines may be effective in addressing post-stroke higher brain dysfunction. Further study is necessary to characterize these agents.

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Subjective assessment and patient-based parameters, including quality of life (QOL), anxiety and depression, have gained attention in the evaluation of functional outcome after treatment of unruptured intracranial aneurysms (UIAs). Patients may become seriously anxious and depressive after notification of the presence of UIAs because of fear for the rupture of their UIAs and the risk of intracranial surgery, thus leading to a consequent decline of cognitive function and QOL. In this prospective investigation, we assessed alterations in peri-operative depression and its influence on cognitive function in patients with asymptomatic UIAs.
Consecutive 100 patients with asymptomatic UIAs (mean age: 58.9 years) underwent clipping through supratentorial approaches between August 2003 and July 2008 at our institute. Among these patients, 117 UIAs located in the anterior circulation except for 2 basilar top aneurysms and 2 posterior cerebral artery aneurysms were approached mostly via the pterional or interhemispheric route. The cognitive test battery consisted of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Kana-hiroi test which is one of examinations of frontal lobe function. Alterations in depression were assessed by Zung’s Self-rating Depression Scale (SDS). Cognitive tests and SDS were performed 2 weeks before, 2 months and 1 year after surgery.
Favorable outcome (modified Rankin Scale 0) was observed in 97 patients 2 months after surgery. The average post-operative total IQ of WAIS-R were significantly increased 2 months and 1 year after surgery, from 93.3 to 96.6 among all patients (p<0.0001) and to 101.1 among 48 patients (p<0.0001), respectively. Also, the average post-operative scores of Kana-hiroi test were significantly increased 2 months and 1 year after surgery, from 23.8 to 26.2 (p<0.01) and to 28.0 (p<0.001), respectively. On the other hand, post-operative changes in depressive mood were various in individual cases. The average SDS was 35.3, 35.4 and 34.5, before, 2 months and 1 year after surgery, respectively. However, inverse correlation of post-operative SDS and alterations in total IQ in individual cases 2 months after surgery was significant (r=-0.384, p<0.0001).
Surgical treatment of UIAs is well-established and does not impair cognitive function. However, peri-operative increased depression in some cases may lead to deterioration in cognitive function and a consequent QOL decline.

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Japanese Nursing Association (JNA) established the Certified Nurse System in 1995, aiming at educational preparation of nurses with proficient knowledge and skills in a particular area of nursing in order to expand the scope of nursing practice and promote the quality care. In 2008, JNA approved the Stroke Rehabilitation Nursing as one of the specialized areas. In 2009, the educational programs are to open, expecting Certified Nurse in Stroke Rehabilitation Nursing (CN in SRN) in 2010. The special knowledge and skills required of the CN in SRN include pathological assessment and prevention of falling into critical state based on the continuous monitoring. In addition, they would be expected to possess such good knowledge and skills of rehabilitation as to improve the movement disorder and the disturbance of higher brain functions, enhancing the self-care capacity of patients and restructuring the life style as a whole, while helping the family members. Moreover, CN in SRN needs to advocate for the dignity of patients and the possibility of the improvement from the disease/disability, and help patients obtain the highest level of ADL and QOL as possible. Early diagnosis and intervention together with early rehabilitation is essential, where the multidisciplinary team including the CN in SRN is of great importance.

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Stroke unit (SU) with both stroke patient’s ward (or beds) and stroke team could significantly improve the outcome by decreasing mortality and increasing patients back to home with independent life in former clinical studies. In Japan, an additional payment to stroke care unit (SCU) which has the same definition as SU was introduced in public health insurance system from May, 2006. In our hospital, SCU with 6 beds and specific stroke team were organized in 2 acute patients wards composed with total 41 beds and registered from Jun, 2006. SCU was integrated with a special ward such as intensive care unit (ICU) with 14 beds for managing stroke patients with conscious disturbance or respiratory distress, IV thrombolytic therapy, and perioperative management of acute surgical or endovascular treatments. Main function of SCU was set up for acute physical rehabilitation, prevention of complications such as pneumonia, and pharmacotherapy for secondary prevention. From May, 2006 to Nov, 2008, 1,166 patients were managed in SCU. NIHSS of patients at admission was 6.3±7.0 in all stroke patients, 5.4±6.4 in patients with cerebral infarction, and 9.8±7.6 in patients with cerebral hemorrhage. Admitted period in SCU was 8.1±3.5 days in all patients, 8.1±3.6 days in patients with cerebral infarction, 8.3±3.2 days in patients with cerebral hemorrhage. Total admitted periods in hospital was 61.1±68.6 days in the first half of the investigation period (to July, 2007) and 52.5±51.8 days in the second half of the investigation period (from Aug, 2007). The outcome (mRS) at discharge was 56% in mRS 0–2, 40% in mRS 3–5, 4% in mRS 6 (death). In our stroke center, patients with mild to moderate severity were managed in SCU. After the introduction of SCU, shortening of total admitted periods in hospital and improving tendency of the outcome was observed. Stroke center equipped with SCU should be promptly organized nationwide corresponding to stroke emergency.

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Since October, 2005 when intravenous thrombolysis with rt-PA (IV-rtPA) for hyperacute stroke was approved, acute stroke care system (ASCS) has been under remodeling in Japan. We conducted a nation-wide survey to reveal the status of 5,398 acute hospitals in 2006. In this study, we investigated the differences in ASCS by population density. The replies of the questionnaires in terms of ASCS were divided into three groups based on the population density; highest tertile (H), middle tertile (M) and lowest tertile (L) groups. The answers of hospitals attending stroke patients were compared among the three groups. 1,586 hospitals (29.4%) responded. The upper and lower tertile thresholds were 2,050 and 461 people/km², respectively. 65% of H group, 75% of M group and 76% of L group attended acute stroke patients (p=0.0001). 47%, 43%, and 50% had direct telephone line with the emergency services, respectively (ns). The early admission rate, within 3 hours of onset, over 20% of all was seen in 23%, 23% and 26%, respectively (ns). Stroke expertise physicians were available on a 24/7 basis in 56%, 63% and 45%, respectively (p<0.0005). 20%, 17% and 9% had Stroke unit, respectively (p<0.001). 9.5%, 7.1% and 2.4% treated more than 10 stroke patients with IV-rtPA per year, respectively (p<0.0001). In conclusion, the acute stroke care system was unsatisfactory, especially in the lowest tertile group by population density, at present in Japan.

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The early CT findings of cerebral infarction include an obscuration of the lentiform nucleus, slight decrease in tissue attenuation, and effacement of the cortical sulci. Dense middle cerebral artery (MCA) sign is an early marker of thromboembolic occlusion of MCA. A novel adaptive partial median filter can improve detection of slightly hypoattenuated areas. Z-score mapping based on a voxel-by-voxel analysis can also help evaluate hypoattenuation areas. Perfusion CT can provide information about brain perfusion, which permits differentiation between ischemic penumbra and irreversibly damaged brain tissue. CT angiography can help detect occlusive or severely stenosed vessels, with collateral pathway via leptomeningeal anastomosis. Potential usefulness of 320-row detector CT in evaluating ischemic cerebrovascular disease is also described.

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Positron emission tomography (PET) has contributed to the solution for the pathophysiology of the ischemic brain with defining the ischemic penumbra, cerebral perfusion reserve, and uncoupling state between cerebral blood flow (CBF) and cerebral oxygen metabolism. Recently, ¹⁵O-PET study in the hyperacute stage of cerebral infarction has elucidated the deterioration of oxygen metabolism in the areas with infarct growth, which phenomenon was called as ‘metabolic penumbra’. New PET imaging of the peripheral benzodiazepine receptor has proved the increase of the activated microglia in the areas with metabolic penumbra, and it may have a potential to become a biomarker of the pharmacological effect in this area. Brain energy metabolism has reevaluated on the basis of the relationship between neuron and astrocyte, and an important role of the astrocyte in the lactate production and recycle of glutamic acid has been reported. ¹¹C-labeled acetate may provide information of TCA cycle of the astrocyte and the activation of glutamine-glutamic acid cycle. PET study for the cerebrovascular disease stepped into a new era by using a novel tracer for molecular imaging.

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Background: The drawbacks of assessing cerebral ischemia using conventional methods such as SPECT or angiography are invasiveness and the inability to repeat measurements. Here, we describe the use of near infrared optical topography (OT) to overcome these disadvantages.
Methods: Twenty-five normal volunteers and 32 patients with cerebral ischemia were enrolled in this study of a 48-channel OT system covering the bilateral fronto-temporal areas. The participants inhaled pure oxygen for 2 minutes and fingertip SpO₂ values were monitored. All of the patients with ischemia underwent IMP-SPECT.
Results: The concentration of oxy-hemoglobin determined by OT and the time course of SpO₂ in normal individuals increased in a trapezoidal manner in accordance with oxygen inhalation, whereas the increase in oxy-hemoglobin was delayed and/or the peak was lower in ischemic areas. These findings suggested that transmission of the systemic SpO₂ wave was delayed and/or reduced in areas of ischemia. Statistical evaluation of the data using principal component analysis showed that the weight of the principal component in the ischemic regions was reduced, findings that agreed with those of IMP-SPECT.
Conclusions: Our results suggested that regional attenuation of the oxy-hemoglobin wave reflects the status of cerebral ischemia, which can be noninvasively assessed using near infrared OT.

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The stroke is divided into the acute period, the convalescence period, and the maintenance period from a rehabilitation point of view. 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, 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.

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The stroke rehabilitation is performed by the multidisciplinary team, and also its stream must be seamless from acute to recovery and chronic stages. Recently in Japan, because of the functional individualization of the hospitals, the stroke rehabilitation has been performed on the local basis. The clinical pathway is one of the tools for the information transmission of the stroke patients among local hospitals. In this paper, I described the knowledge of the rehabilitation necessary for the clinical pathways for the local stroke network as follows: 1) the rehabilitation in each phase of stroke, 2) the discharge planning, 3) assessment tools for stroke disabilities, 4) multidisciplinary team approach, 5) sharing the information and 6) usage of information on personal independence in activities of daily living. Particularly, the understanding of the stream of stroke rehabilitation is most important timely to provide the stroke patients with appropriate rehabilitation.

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Tokyo has some special aspects in comparison with the other areas in Japan. As of February 1^st, 2009, Tokyo had a population of 12,909,940, and about the 2/3 lives in Tokyo 23 wards. In this area, the number of ambulance transport, especially for elderly patients is increasing. But the number of emergency hospitals is decreasing sharply year by year. Under such a situation, the result of fact-finding report about medical care function in Tokyo metropolitan area demonstrated that some hospitals for acute illness in Tokyo had their own networks including cooperation hospital to smoothly transfer patients. Our department has already built the big wide cooperation, as the board-certificated physiatrists belonging to our department were posted in the hospital of not only in Tokyo 23 wards but also in six prefectures around Tokyo. Revising this previously-built network, we were able to make a new network, MSN, which covers broader area than the previous one. Although the form for MSN is very easy to complete, it contains some international evaluation scales such as Barthel Index, NIHSS and ABMS. Now the number of hospitals participating MNS exceeded 60. We aim to strengthen cooperation with rehabilitation hospitals dealing with stroke patients in chronic phase.

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In this article, the authors reviewed the historical aspects and the concepts of clinical pathways for local network in Japanese health system. Furthermore, the authors described how they including Kitakyushu Medical Association, the University of Occupational and Environmental Health and Kitakyushu City, cooperate and how they form the system of clinical pathway for local network in Kitakyushu City, in which about one million people live in southern part of Japan.

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InCliPS (Inba Clinical Pathway for local Stroke network) has been utilized among the hospitals in suburban area at Chiba Prefecture. The organization of transferring the stroke patients from acute to rehabilitation hospitals might be improved by the implementation of this clinical pathway. This regional clinical pathway has been useful not only to compile the information about hospitalized medical records but also to investigate the rehabilitation outcome. Following pathway implementation there have been clinically important, but not statistically significant, allied health assessment and decrease hospitalized periods in convalescent rehabilitation hospitals. It is necessary to cooperate among the acute and convalescent rehabilitation hospitals in order to organize the networks for global stroke medical care through the regional clinical pathway. There, however, have been various difficulties for promoting this network because there have been a lot of regional clinical pathways. It is needed to establish the prefectural common clinical pathway for stroke among the hospital networks to reduce the complicated problems. The prefectural common clinical pathway has just been propelled in the project team consisted of the acute and rehabilitation hospitals and prefectural committee.

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We have developed a community organization of stroke care with coordinated inter-institutional service, which provides a critical and predictable pathway of acute and rehabilitation hospital treatments for patients suffered from stroke. After adequate treatment in stroke unit and ward, patients with moderate or sever disability are transferred to a multidisciplinary rehabilitation hospital with the programmed total care period of 60 days, 90 days, or 180 days according to the disability. The patient’s medical and functional information such as Functional Independence Measure (FIM) are shared among the hospitals by internet-based, information collaboration software, Microsoft Office Groove^®, in secure and decentralized manner, providing a seamless service for the patients.
The hospital stays were shorter for patients assigned this service than for those assigned conventional care both in the acute hospital by 37% and in the rehabilitation hospital by 24%. It is, however, not yet clear whether this service improves outcome of the patients compared with traditional rehabilitation service.

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Atherothrombotic occlusive disease of the intracranial arteries is common in Japan, Asia, and black people. In 1,046 patients with acute atherothrombotic brain infarction between 2006 and 2008, intracranial arterial occlusion (53%) was more common than extracranial occlusion (47%). In patients with intracranial occlusion, occlusion of the middle cerebral artery occupied 59%, that of the vertebral artery 16%, that of the posterior artery 14%, the basilar artery 10% and the anterior cerebral artery 1%. In acute phase of atherothrombotic stroke, tissue plasminogen activator may be applied within 3 hours of onset, edaravone within 24 hours, argatroban within 48 hours, ozagrel sodium with heparin within 5 days, and oral antiplatelet agents at anytime. Hemodilusion therapy, statin treatment, and therapy against brain edema are also considered. After acute phase, to prevent recurrent attacks, appropriate oral antiplatelet agents, such as aspirin (75–150mg/day), clopidogrel (50–75mg/day), or cilostazol (100–200mg/day) are administered. Control of risk factors, hypertension (blood pressure less than 140/90mmHg), diabetes mellitus (HbA1c less than 7.0%, dyslipidemia [LDL cholesterol less than 120mg/dl]) are quite important. Cessation of smoking habit is also strongly required.

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Background and purpose: Although intracranial atherosclerotic disease has been highlighted especially in Asian countries, little is known about the stroke mechanism of middle cerebral artery (MCA) stenosis. Patients with MCA stenosis often show acute neurological worsening. However, no study has ever been focused on stroke mechanism and acute neurological worsening in patients with MCA stenosis. We conducted the present study to clarify the relationship between stroke mechanism and acute neurological worsening in patients with MCA stenosis.
Methods: From consecutive acute ischemic stroke patients entered in our hospital, we selected 30 patients who had MCA stenosis. Patient characteristics, clinical course and lesion patterns were correlated.
Results: Acute neurological worsening was observed in 10 patients (30%), of whom 8 patients exhibited poor prognosis. Diabetes mellitus tended to be significantly associated with acute neurological worsening. Subcortical small multiple infarcts, deep border-zone infarcts and striatocapsular infarction tended to be significantly associated with acute neurological worsening.
Conclusion: Two main stroke mechanisms appear to contribute to acute neurological worsening in patients with MCA stenosis. One mechanism is a combination of hypoperfusion and micro-embolism. The other mechanism is occlusion of multiple lenticulostriate arteries by MCA plaque. Clarifying mechanism may help to decide therapeutic strategies.

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The purpose of this study is to assess perioperative and long-term outcome of balloon angioplasty without stenting for symptomatic middle cerebral artery (MCA) stenosis. We retrospectively analyzed the clinical and angiographic data of 58 patients (mean age 59 years old) with 66 balloon angioplasty without stenting for high-grade (>70%) atherosclerotic stenosis of the main trunk of MCA between 1993 and 2007. All patients had experienced recurrent transient ischemic attack (TIA) or minor stroke resistant to medical treatment and significant perfusion problems in MCA territory. The period of follow-up was mean 64 months (6–171 months) in 50 patients. Balloon angioplasty was successfully in 89%. Symptomatic dissection with major stroke occurred in 1 patient. Minor stroke without neurological deterioration occurred in 2 patients. Asymptomatic dissections occurred in 5 patients. Restenosis occurred in 10 patients at mean 19±12 months after treatment. Occlusion of MCA occurred in 5 patients at mean 50 months. Recurrent of stroke and TIA occurred in 6 patients at mean 52 months. Balloon angioplasty without stenting for symptomatic MCA stenosis can be performed with a high successful rate and a low risk of complications. Long-term clinical follow-up data suggest that this procedure reduces the risk of further stroke.

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Intracranial branch atheromatous disease (BAD) was proposed by Caplan in order to clarify problematic cases that do not fit into the dichotomatous separations of cases into lipohyalinotic penetrating artery disease or large artery occlusive disease. Narrowing or occlusion of the mouth of the branching artery by an atheromatous plaque results in deep infarcts of more than 10mm diameter with classical lacunar syndromes including pure motor hemiparesis. Both lenticulostriate and paramedian pontine arteries are likely to be involved in BAD. Neurological worsening after admission and poor functional outcome at discharge are usually observed in BAD patients. Once the patients show any neurological or radiological sign of BAD, they are treated intensively with anti-thrombotic drug and edaravone. Plaque stabilization and improvement of endothelial function would be the therapeutic targets for treatment of BAD in the future.

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For the prevention of cardiovascular events, especially stroke, strict blood pressure control is essential. In this review, recently published Japanese guidelines for treatment of hypertension is summarized, focusing on primary and secondary prevention of stroke. In the chronic phase of cerebrovascular disease (1 month or moreafter onset), the eventual target of blood pressure control should be <140/90mmHg. Blood pressure should be lowered carefully and slowly, paying attention to the stroke type such as cerebral hemorrhage, lacunar infarction, etc. The presence or absence of stenosis/obstruction of a main trunk of the cerebral arteries and the presence or absence of symptoms of cerebral circulatory insufficiency are also important. If the bilateral carotid arteries are markedly narrowed, or a main trunk of the cerebral arteries is obstructed, caution against an excessive decrease in blood pressure is necessary. A target of blood pressure control even lower than 140/90mmHg is recommended for patients with lacunar infarction or cerebral hemorrhage. Antihypertensive drugs recommended in the chronic phase of stroke are calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, etc.

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Recommended measures for control of blood pressure in stroke patients at the superacute, acute and chronic stages were presented in two guidelines in 2004 (The Guideline for the Management of Hypertension and The Guideline for the Management of Stroke). We have investigated the discrepancy between actual clinical practice and the above recommendations.
We examined the clinical outcome and the incidence of symptomatic hemorrhage in patients with and without antihypertensive drug treatment before the administration of rt-PA in superacute stroke patients. We analyzed 47 patients with acute stroke treated within 3 hours after onset. According to the guideline, antihypertensive agents are indicated in patients with hypertension over 180mmHg systolic or 105mmHg diastolic pressure. Six patients showed the indication for antihypertensive therapy. There was no significant difference in prognosis measured in terms of mRS (0–1) at 3 months and the incidence of symptomatic hemorrhage between two groups. The recommended level of blood pressure in the guidelines is therefore considered appropriate for these patients.
Anti-hypertensive therapy in the acute phase within one or two weeks after onset has not been done in principle, except in special circumstances as described in the guidelines. We chose to examine the propriety of early anti-hypertensive therapy for patients with lacunar stroke, based on the tendency for shorter duration of hospitalization in acute hospitals, and because of the introduction of the seamless stroke collaboration system for treating stroke patients and the results of the ACCESS study, which showed that early intervention with ARB had a favorable effect on prognosis. We divided 100 patients with lacunar stroke into two groups according to the level of blood pressure. We prescribed anti-hypertensive agents (ARB or Ca channel blocker) in patients with over 180mmHg systolic or 105mmHg diastolic pressure within 2 weeks after onset. There was no significant difference in clinical outcome at 3 months or in the recurrence rate of stroke at one year between the two groups. The results suggested that early intervention with antihypertensive agents could be safe and appropriate in patients with lacunar stroke. However, this should be confirmed with more patients and a clinical trial.
As regards the goal for blood pressure in the chronic stage for the secondary prevention of stroke, the Japanese Guideline for Treatment of Hypertension recommended that the final goal should be under 140/90mmHg. Recent subanalysis of the PROGRESS study suggested that lowering the level to 120mmHg systolic pressure might be preferrable. However, Japanese and American Guidelines for Stroke Management have not given a precise goal for blood pressure, because of individual differences among patients. We think a new guideline recommending a lower level of blood pressure in certain kinds of stroke types and clinical situations is needed.

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Both hypertension (HT) and chronic kidney disease (CKD) are associated with an increased risk of cardiovascular diseases including stroke. Our objective was to examine, using the data of Fukuoka Stroke Registry (FSR), the association between these risk factors and the clinical manifestations and outcome of acute ischemic stroke patients. 1,410 consecutive patients with cerebral infarction were enrolled. HT and CKD were observed in 74.0% and 32.1% of the patients with cerebral infarction, respectively. The patients with HT (HT group) had higher frequencies of diabetes and dyslipidemia than those without HT (non-HT group). The frequency of atherothrombotic infarction in HT group was higher than in non-HT group. Severity and activity of daily living (ADL) were similar between HT and non-HT groups. On the other hand, the patients with CKD (CKD group) had higher frequency of cardioembolic stroke than those without CKD (non-CKD group). NIH stroke scale of CKD group was higher than non-CKD group and ADL of the patients with CKD was worse than those without CKD. Thus, HT and CKD may have a different impact on ischemic stroke.

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Recently, several cohort studies revealed that predialysis chronic kidney disease (CKD) is closely associated with cardiovascular diseases, as well as stroke. On the other hand, it has been well recognized that CKD under regular dialysis is on the burden of stroke. Here we summarize recent reports regarding the relationship between stroke and CKD.

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CHADS₂ Score is used for the risk stratification and treatment recommendation in patients with non-valvular atrial fibrillation (NVAF). NVAF patients with CHADS₂ Score ≥2 are at high stroke risk and recommended warfarin for stroke prevention. Those with CHADS₂ Score 1 are recommended aspirin or warfarin. However, according to the results of the Japanese Atrial Fibrillation Stroke Trial (JAST), aspirin did not reduce stroke risk and tended to increase bleeding risk in low-risk NVAF patients. Therefore, warfarin is recommended even in those with CHADS₂ Score 1. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) Study showed that incidence of ischemic stroke was much lower in warfarin (INR 2–3) group than in aspirin group and incidence of hemorrhagic stroke was similar between both groups among elderly NVAF patients. The results of BAFTA indicated that warfarin is recommended even in elderly NVAF patients.
Efficacy of antiplatelet therapy for primary stroke prevention has not established in patients with asymptomatic brain infarction, carotid disease, or vascular risk factors alone. Thus, we conducted the Japanese Primary Prevention Project with Aspirin in the Elderly with One or More Risk Factors of Vascular Events (JPPP), a large randomized trial of aspirin for primary prevention of vascular events including stroke. However, there is a possibility that a risk reduction of vascular events is less than an increase of bleeding risk in primary prevention. Then, we conducted the Management of Aspirin-Induced Gastro-Intestinal Complications (MAGIC), a multi-center cooperative observational study on endoscopical investigation of gastrointestinal complications with aspirin in patients with vascular diseases including stroke.

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Platelets play a crucial role in arterial thrombus formation as a final step of atherosclerosis. Atherosclerosis is initially triggered by dysfunctional endothelial cells via inflammatory processes. Recent studies demonstrate that platelets also play an important role in the initiation of atherosclerotic lesion by releasing inflammatory mediators. Thus, atherosclerosis and thrombosis are interdependent (atherothrombosis). As an initial step in thrombogenesis, platelets adhere to altered vascular surfaces or exposed subendothelial matrices. Following adhesion, they become activated, change shape, secrete granule contents, and aggregate to each other to form thrombi and provide a catalytic surface to enhance blood coagulation. A number of adhesive proteins [e.g. von Willebrand factor (VWF), collagen], cell-adhesion receptors (e.g. GPIb-IX, a_IIbb₃), and platelet receptors (e.g. P2Y₁₂, GPVI, PAR1) are involved in thrombus formation. This review article describes molecular mechanisms for thrombus formation and the targets of newly developed anti-platelet agents.

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The Hokkaido Branch of the Japan Stroke Association has established supporting systems for PCEC/PSLS in Hokkaido. Kindly supported by PCEC Tokyo and PCEC/PSLS Shizuoka, we held “The 1^st PCEC/PSLS Hokkaido/Sapporo” on February 7^th 2009 which consisted of simulation trainings on cases of acute stroke and coma, including lectures on GRTPA (alteplase). There are some problems facing neurosurgeons and stroke physicians who are willing to join PCEC/PSLS, which we attribute to differences in systems between doctors and ambulance crews, or neurosurgeons and ER doctors, such as gliding work schedules or physician-in-charge system that represents unique style of medical care in Japan.

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