Seventy-three cases with asymptomatic cerebral infarction detected by MR scanning and 80 cases of past stroke patients were evaluated. The regional cerebral blood flow (CBF) using the SPECT, idoine-123-IMP autoradiography (ARG) method was measured. Twenty-two patients with non-specific complants (dizziness, numbness of the extremities, headache, etc.) without cerebrovascular risk factors were also examined as controls. Fifty-two percent of the asymptomatic infarction cases had non-specific complaints. The regional CBF in all cerebral non-specific complaints showed significantly lower values as compared to the controls. There was no difference in CBF values between the asymptomatic infarction cases with non-specific complaints and the past stroke patients. Among the asymptomatic infarction patients, cases with both non-specific complaints and hypertension displayed significantly lower CBF values, especially in the frontal and temporal cortical regions, than did cases without non-specific complaints or hypertension. These findings suggest that the patinet's complaints should be taken into consideration when determining the clinical treatment of asymptomatic infarction.

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We examined the effects of aspirin and ticlopidine on the platelet aggregability during daily antiplatelet medication for 2 weeks. Eighteen post-thrombotic stroke patients were studied : 10 patients received 330 mg aspirin once a day, and 8 patients received 100 mg ticlopidine twice a day. The platelet aggregability was measured by the laser scattering method (AG-10, Kowa Ltd.) and by the opital method. With the laser scattering method, we were able to detect small, medium, and large size particles of aggregates. The aggregation of platelet-rich plasma (PRP) was estimated after stimulation with collagen (1, and 2 μg/ml) and ADP (0.5, and 5.0 μM) before, and at 1, 2, 4, 7, and 14 days after antiplatelet medication. In addition, the effects of aspirin on the platelet aggregability were measured before and at 1, 2, 3, 4, 6, and 12 hours after the administration. Aspiria significantly reduced (p<0.05) both the platelet aggregability by the optical method and the formation of medium and large platelet aggregates induced by 1 μg/ml collagen at the 1st day after antiplatelet medication, but had little effect on the formation of small platelet aggregates. Furthermore, aspirin began to reduce significantly (p<0.05) after the 1st hour both the platelet aggregability and the formation of large platelet aggregates induced by 2 μg/ml collagen. Ticlopidine revealed no significant reduction in both the platelet aggregability and the formation of all platelet aggregates induced by 0.5, and 5.0 μM ADP on the 1st day, but the aggregability by the optical method was significantly reduced (p<0.05) on the 2nd day, and particularly on the 4th day. The above results suggest that the antiplatelet effects of aspirin and ticlopidine may have different kinetics.

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The purpose of the present study was to determine whether or not a neuropsychological battery of examinations could demonstrate abnormalities in diabetic patients with silent cerebral infarction and which examinations were the most useful for screening such abnormalities. In addition, we analyzed whether or not diabetic microangiopathy (retinopathy, nephropathy, and neuropathy), hypertension and aging affected the scores on the neuropsychological battery. We classified 48 diabetic patients into three groups according to ther magnetic resonance imaging (MRI) findings, as follows : 16 cases with no infarction (Grade 0 : G0), 12 cases with a few lacunar infarctions (Grade 1 : G1), and 20 cases with over 5 lacunar infarctions (Grade 2 : G2). Five neuropsychological examinations (the mini mental state examination (MMS-E), word fluency test, digit span, modified Stroop test, and Kana-Hiroi examination) were applied to the diabetic patients. Although the MMS-E revealed no difference in scores among the three groups, the digit span and word fluency tests showed declines in scores, which correlated with the deterioration seen on MRI. On the other hand, aging and complication of microangiopathy or hyperension did not significantly affect the scores on the neuropsychological battery regardless of the MRI findings. The present data revealed that some diabetic patients with silent cerebral infarction had mild neuropsychological abnormalities and that both the digit span and word fluency tests were the most useful for screening such mild neuropsychological abnormalities.

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The effects of antithrombotic therapies on the prevention of stroke incidence in patients with chronic non-valvular atrial fibrillation were evaluated retrospectively. No significant differences in rates for all ischemic strokes, brain embolism, brain thrombosis and brain hemorrhage were found among the following 3 groups : aspirin-treated (n=53; mean daily dose, 117 mg), ticlopidine-treated (n=87; mean daily dose, 178 mg) and non-treated patients (n=378). On the other hand, the warfarin-treated group displayed a marked reduction in incidence of ischemic stroke, although most patients had low-intensity anticoagulation lower than 2.0 as mean INR. In the primary prevention of ischemic stroke, the annual rates for brain infarction and embolism in 67 warfarin-treated patients were significantly lower than those in 371 non-treated patients (2.23% versus 6.12%, and 0.74% versus 4.12%, respectively, p<0.05). In the secondary prevention, the warfarin therapy significantly reduced the annual rates for brain infarction from 14.56% to 1.62%, and for brain embolism from 12.13% to 1.62% (p<0.01). Importantly, the yearly incidence of brain hemorrhage showed no significant change between warfarin-treated and non-treated patients in both the primary and secondary prevention trials. We therefore recommend low-dose warfarin therapy for the prevention of brain infarction, especially of brain embolism, in patients with chronic non-valvular atrial fibrillation.

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Magnetization transfer (MT) contrast images of the brain were obtained in 17 patients (30 studies) with supratentorial cerebral infarction, and the changes in MT effects (Moff-Mon/Moff) expressed as the ratio of lesion to control (L/C ratio) were assessed over time. Acute infarct lesions could not be detected or were relatively slight on the MT contrast images. However, subacute and chronic infarcts were shown with a low signal intensity, and the L/C ratios at these periods were significantly lower than those in at the acute stage. A significant correlation was noted between the L/C ratio and days after onset of stroke. MT contrast imaging is useful in the assessment of ischemic stroke, particularly at the subacute and chronic stages, and can assist in determining the age of cerebral infarcts.

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At the acute phase of cerebral thrombosis, endothelin-1 (ET-1), a vasopressor factor derived from vascula : endothelial cells, decreases with time. On the other band, tissue plasminogen activator (t-PA), a rate-determining factor of fibrinolysis, increases enantiomorphically. Elucidation of the mechanism involved is important for analyzing and for determining the guidelines for the treatment of the disease. In the present study, in an attempt to analyze the above mechanism, we conducted a basic clinical study. Release of both factors was not altered by the addition of sodium ozagrel or thrombin to cultured vascular endothelial cells. From this finding, it is denied that therapeutic drugs and coagulation may be associated with an increse in free PAI-1 which reflects the activity of PAI. In combination with previously reported results showing a decrease in the release of ET-1 following addition of t-PA, the data suggest that t-PA may influence an inhibitory effect on fibrinolysis when both factors change at the acute phase. It is considered that the increased t-PA may inhibit predominantly the relcase of ET-1 and induce resistance against thrombosis at the acute phase. In the treatment of cerebral thrombosis, we should therefore consider not only antiplatelet effects and anticoagulation but also such increase in t-PA.

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We examined the effectiveness of the histamine H₂ receptor antagonist, ranitidine, as a pre-ischemic treatment on the cerebral blood flow (CBF), brain energy metabolism, and brain parenchymal specific gravity following transient forebrain ischemia in 59 adult male Mongolian gerbils. Ranitidine (5 mg/kg) or an equal volume of saline was administered intraperitoneally at 30 min prior to ischemia. The sequential changes in phosphocreatine (PCr) /inorganic phosphate (Pi) ratio, β-ATP/Pi ratio, and intracellular pH (pHi) were determined by ³¹P NMR spectroscopy. CBF was measured continuously with a laser-Doppler flowmeter. The brain specific gravity was evaluated at 120 min after reperfusion. In the ranitidine-treated group, the PCr/Pi ratios were significantly higher at 40 min after reperfusion and the pHi was significantly higher at 10, 20, and 30 min after reperfusion than those in the saline-treated group. The brain specific gravity was greater than that in the saline-treated group. These findings suggest that ranitidine may reduce the brain edema and improve the recovery of brain energy metabolism and pHi from an early stage of reperfusion following transinet forebrain ischemia.

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We evaluated the differences in effects of the competitive inhibitor, argarroban, and the cyclooxygenase inhibitor, aspirin, on the cerebral blood flow (CBF), cerebral energy metabolism, and edema formation following transient forebrain ischemia in mongolian gerbils. Argatroban (3 mg/kg; argatroban-treated group), aspirin (5 mgkg; aspinin-treated group), or saline (saline-treated group) was infused intravenously. CBF was measured continuously and the cerebral specific gravity was evaluated at 120 min after reperfusion. The sequential changes in cerebral energy metabolism, as indicated by the PCr/Pi ratio, β-ATP/Pi ratio and pHi, were also determined. In the argatroban-treated group, the CBF returned more rapidly to the preischemic level after reperfusion as compared to the other groups (recovery time= 19.2 ± 10.6 min), and no reactive hyperemia was observed. Recovery of the CBF in the aspirin-treated group was faster than in the saline-treated group after reperfusion. Decreases in pHi, PCr/Pi, and β-ATP/Pi were observed during bilateral common carotid artery occlusion. The pHi, PCr/Pi ratio, and β-ATP/Pi ratio showed significantly better recovery (p<0.01) in the argatroban-treated group after reperfusion as compared to the other groups. The brain specific gravity in the argatroban-treated group was significantly higher than in the other group (p<0.01). The brain specific gravity in the aspirin-treated group was higher than in the saline-treated group (p<0.01). Argatroban was more effective in ameliorating postischemic cerebral edema than was aspirin (p<0.01). These findings clearly demonstrate that benefical effects of argatroban are greater than those of aspirin following transient forebrain ischemia.

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Asymptomatic cerebral ischemic lesions, which consist of asymptomatic cerebral infarction (ACI) and most periventricular hyperintensities (PVH) on T₂-weighted MRI images, are commonly recognized in patients with first-ever stroke. Although many reports have appeared on the CT characteristics of ACI, the epidemiologic features of ACI as observed by MRI and their relation to atherosclerosis in such patients remain unclear. In the present study, we retrospectively investigated the characteristics of such lesions on MRI, and the relation to risk factors and atherosclerosis on ultrasonography or angiography in 43 patients (mean age, 65 ± 13 years) with first-ever ischemic stroke. The frequency of ACI was 67.4% (29/43). The most common site of ACI was the subcortical white matter, and the maximum size of ACI was≤15 mm in 93.1% of cases. In association with ACI, the odds ratios of atherosclerosis (odd ratio [OR], 8.40) and hypertension (OR, 2.96) were high. The overall prevalence of PVH was 74.4% (32/43), and PVH was significantly associated with ACI (OR, 6.25; 95% confidence interval [CI], 1.41 to 27.65). Hypertension (OR, 13.50; 95% CI, 2.46 to 76.04) and atherosclerosis (OR, 20.67; 95% CI, 1.95 to 218.72) on univariate analysis, and age (p= 0.0049), male sex (p= 0.0398), hypertension (p = 0.0081) and diabetes mellitus (p=0.0181) on Spearman's rank correlation, were significantly associated with PVH. In the present study, the frequency of ACI on MRI was very much higher than that in reported CT studies, and atherosclerosis was associated with ACI and PVH. Although atherosclerosis is not necessarily responsible for ACI and PVH, patients with ACI or PVH on MRI should be investigated for large-vessel disease.

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Psychiatric and subjective symptoms such as headache, dizziness, lack of spontaneity, anxiety, and a depressive state are often found in patients with chronic cerebral infarction. Some Ca antagonists are reported to relieve such symptoms. The purpose of the present study was to investigate the relarionship between psychiatric and subjective symptoms and cerebral blood flow (CBF) in cerebral infarction and to evaluate the clinical effects of Ca antagonists from the standpoint of the cerebral circulation. Nilvadipine was administered to is patients with chronic cerebral infarction and their CBF was measured by the ¹²³ IMP-SPECT ARG method before and at 8 weeks after the nilvadipine treatment. The CBF in patients with hypertension was increased by 11% after giving nilvadipine. Patients without hypertension showed no tendency for elevation of their CBF. Patients who were relieved from some psychiatric symptoms revealed a 14% increase of CBF in all cortical regions, and a significant increase was noted in the frontal and termporal regions. In other patients without changes in psychiatric symptoms, the CBF did not increase in any of the cortical regions. No relationship between symptoms and CBF was observed in any of the patients with subjective symptoms. Our study demonstrated a close correlation between psychiatric symptoms and CBF. We speculate that psychiatric symptoms in chronic cerebral infarction may reflect diffuse brain dysfunctions. We also conclude that nilvadipine is more effective in relieving psychiatric symptoms in patients with hypertensive cerebral infarction. It is inferred that nilvadipine may be more effective in relieving psychiatric symptoms in patients with hypertension.

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There are rare reports concerning the carotid ultrasonographic findings after carotid endarterectomy (CEA). We analyzed the ultrasonographic findings following CEA, and investigated the factors that influence plaque formation (sex, age, intervals of operations, atherosclerotic risk factors, thickness of the intima-media complex, and antiplatelet agents). The subjects comprised 62 patients (54 men, 8 women; mean age, 70 ± 7 years), and the intervals after CEA were 24 months. We classified the carotid artery into 3 parts : the common carotid artery (CCA), bifurcation (BIF), and internal caroid artery (ICA), and then measured the plaque scores (sum of plaque thickness). Plaque formations were detected in all parts at the early stages. We precisely observed the various plaques. The plaque scores were not correlated with the intervals after the operations and various risk factors. Our results demonstrated that plaque formation after CEA exists from the early stages, may not enlarge gradually, and may not be produced by atherosclerotic changes as usual but by the restitution process following CEA.

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Isolated sensory hearing loss is usually associated with inner ear disorders we report two patients with clinical features of brain infarction in the distribution of the anterior inferior cerebellar artery (AICA), who had unilateral sensory hearing loss as an isolated symptom for several days or months prior to stepwise development of typical AICA infarction syndrome. Patient 1 was a 65-year-old hypertensive woman who was hospitalized at 10 days after the onset, because of vertigo, dysarthria, left hemiataxia and truncal ataxia, she initially developed left hearing loss at 20 days prior to admission. At 1 day after admission, she further developed left peripheral facial palsy, patient 2 was a 69-year-old hypertensive man with diabetes mellitus and hyperlipidemia. He suffered from right hearing loss at is months prior to admission, and then had sudden onset of vomiting and truncal ataxia. At 1 day after admission, he developed right facial numbness, right hemiataxia and left peripheral facial palay. In both patients, the final neurological features were compatible with AICA infarction syndrome. MRI demonstrated hyper-intense lesions in the lateral pons and middle cerebellar peduncle on T2-weighted images. Cerebral angiography confirmed a unilateral occulusion of the AICA in both patients. A combination of peripheral and central symptoms and signs, including VII and VIII nerve involvements, is characteristic of AICA infarction syndrome. Isolated sensory hearing loss may precede the full AICA infarction syndrome, depending on the anatomical variation of the branches of the AICA.

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