Outcome of over 5, 000 stroke patients admitted to National Cardiovascular Center Hospital during the period of 1978-90 was surveyed. Cerebral hemorrhage was reduced in frequency and cerebral infarction was increased in recent years. Outcome of the patients was, in general, improving, partly because of the milder cases more frequently admitted in recent years, though the average age of the patients became somewhat older. As to the type of stroke, subarachnoid hemorrhage due to ruptured aneurysm showed the highest mortality in its early stage, followed by cerebral hemorrhage or cerebral embolism and cerebral thrombosis in that order. In the cases followed for 5 years or more, the outcome both for life and ADL was the worst for cerebral embolism. Non-valvular atrial fibrillation in the elderly should seriously be considered because it accelerated not only occurrence but also recurrence of stroke. TIA underwent completed stroke in the frequency of 4.5% per year in average.
Bacterial endocarditis could cause stroke, not infrequently unrecognized of the presence of heart disease at the time of onset. Mortality of such a stroke was high. The effects of surgical treatment of subarachnoid hemorrhage, cerebral hemorrhage and occlusive cerebrovascular disease were also described.

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The aim of the present project was to contribute to the eradication of cerebrovascular diseases (CVD) by means of a multi-facted approach. The studies have been conducted on each sub-project described below : 1) definition and diagnostic criteria, 2) cerebral blood flow (CBF) and metabolism, 3) neurochemical and neuropathologic approaches to vascular dementia, 4) effects of aging on arterio-/atherosclerosis of the brain, and 5) treatment and secondary prevention.
Studies performed during the study period are summarized as follows. 1) The definition and diagnostic criteria for CVD was revised referring to findings of modern diagnostic devices such as CT, MRI, PET, etc. 2) CBF and cerebral metabolism in the acute stage of cerebral ischemia were evaluated in relation to the timing of appearance of hypodense area on CT and availability of collateral blood flow on angiograms. Vascular reactivity in acute ischemia and effect of anti-hypertensive therapy on autoregulation were studied in both humans and animals. 3) White matter pathology in demented patients was investigated with neuroimaging, electron microscopy and tissue culture. Neurochemical approaches were focused on intracellular metabolism of protein, neurotransmitters and enzymes in the ischemic brain. 4) Effects of aging on cerebrovascular system were represented by initimal thickning with medial thinning and a decrease in elasticity. Known risk factors were less important in development of stroke in aged population. 5) Progression and regression of arterial lesions were demonstrated by B-mode ultrasound technique and cerebral angiography. Long-term follow-up studies in stroke patients were carried out in relation to recurrence, changes in CT findings and CBF.
Collaborative study (retrospective) on efficacy of anti-platelet therapy was completed, and revealed that this agent was effective in secondary prevention of stroke without increasing risks of brain hemorrhage. On-going prospective study will be continued in the next project.

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This research project has been organized facing the results of the international EC-IC bypass study, in which the effectiveness of the bypass surgery on stroke prevention could not be confirmed in the whole series, while a subgroup of Japan-Taiwan series revealed some benefits of surgery. The research project consists of main three pillars : 1. Newly designed randomized EC-IC bypass Japan cooperative study. 2. Further follow-up of entry cases of the international EC-IC bypass. 3. Individual research project by each investigator participating in the research project.
Newly designed randomized study has been initiated with a new entry criteria with emphasis on the hemodynamic dysfunction as shown in Table 2. Seventy two cases from 30 centers in Japan have entered the study through the end of Sept. 1991.
Individual research projects consists of followings : Projects on 1. Noninvasive, inexpensive, reliable and simple methods to detect hemodynamic dysfunction which is of cardinal importance in selecting candidates of reconstructive vascular surgery. 2. Less invasive, effective, safe, simple and longlasting methods of cerebrovascular reconstruction including the endovascular surgery. 3. Evaluation of the effectiveness of cerebrovascular reconstruction. 4. Experimental cerebral ischemia. 5. Any other items related with cerebrovascualr reconstruction.

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The incidence of strokes among 16, 000 persons in 11 districts across the nation was registered. The frequency by type of stroke was 25% for cerebral hemorrhage, 65% for cerebral infarction and 10% for subarachnoid hemorrhage. The early-stage mortality within four weeks after the onset of strokes stood at 10-20%, whereas the mortality within one year came to 20-30%. The rate of those who require total care (in bedridden conditions) one year after the onset was in the neighborhood of 15%. The higher the age, the higher the rate.
A check of trends in the Saku district of Nagano Prefecture in the last 17 years indicates that the incidence of strokes had slightly dropped but the early-stage mortality has sharply decreased. In terms of the frequency by type of stroke, cases with cerebral hemorrhage were on the decrease but those with cerebral infarction were on the increase.

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Repairing process following a microvascular end-to-end anastomosis of the common carotid artery was serially examined in 96 Wistar rats, weighted 250-350 gm, aged 14 weeks, using transmission electron microscopy (TEM) and immunohitochemical stain besides a light microscopic observation. We were paricularly interested in the process of intimal hyperplasia and re-endothelialization.
Degeneration of the endothelium was observed shortly after anastomosis in the ischemic portion of the artery subjected to a temporary clipping. This was followed by its re-endothelialization, which proceeded for about 10 days.
Intimal hyperplasia started on the 8-9th day mainly in the distal portion of the anastomosed area, and reached a maximum level at about the 14th day, followed by stabilizing thereafter.
Morphological changes observed by TEM indicated that cells originally involved in intimal hyperplasia arose from the increased immature mesenchymal cells of the adventitia. They then migrated through cut portion of the tunica media. More superficial cells of the intimal hyperplasia differentiated into endothelial-like cells, while others differentiated into smooth muscle cells as also indicated by the results of immunohitochemical stain. Since human antibodies were used in this study, including laminin, collagen type IV, factor VIII, S-100 protein, muscleactin. UEA 1, a₁-ACT and desmin, the stainability of the first five antibodies really supported this view.
In conclusion, two types of the cells appeared to be involved in repair of the endothelium injured in microvascular anastomosis. They include : (1) cells arising from normal endothelium surrounding the anastomosed site, as is suggested conventionally, and (2) cells derived from endothelial-like cells originally involved in the intimal hyperplasia which arise from the increased immature mesenchymal cells of the adventitia.

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