The development of arterial recanalization strategies using plasminogen activators for treatment of atherothrombotic and thromboembolic cerebral ischemia has exposed events which contribute to the limitation and extension of tissue injury. These include the presence of early ishemic injury, individualization of the potential window for treatment, edema formation, and the mechanisms underlying the hemorrhagic transformation. The appearance of early ischemic injury and the potential window for treatment seem tied to the patency of collateral channels and peculiarities of the microvascular bed of the individual patient. Hemorrhagic transformation, a common accompaniment of focal cerebral ischemia, is related to the time from symptom onset to exposure with the plasminogen activator, persistence of diastolic hypertension, a relative plasminogen activator dose-rate, extensive ischemic injury on CT, anticoagulation, and advanced age. Limited evidence suggests that a threshold of regional cerebral blood flow reduction is significantly associated with symptomatic intracerebral hemorrhage. These contributors suggest a common vascular target. The microvasculature is both a source of cerebral integrity and the target of ischemic injury. Activation of microvascular endothelial cells by ischemia leads to the expression of P-selectin, ICAM-1, and E-selectin which promote PMN leukocyte firm adhesion and transmigration. Obstruction of microvascular flow is a consequence. Activation of platelets, in relationship to PMN leukocytes, and intravascular fibrin formation contribute further to the loss of microvascular patency. Within the myointima of selected microvessels the integrin α_vβ₃, appears. Constituents of the basal lamina and extracellular matrix, whose loss contributes to hemorrhagic transformation, are affected significantly within the initial 24 hours following ischemic injury. Recently, significant aletrations in cell-matrix interactions between the endothelium and astrocyte end-feet, and their respective matrix partners, have been shown to occur most significantly in the region of severest neuron injury. Interventions which reduce the frequency and severity of these microvascular processes should enhance benefit in acute stroke patients.

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In 13 patients with transient global amnesia (TGA), we studied the clinical course and changes over time by means of imaging techniques such as SPECT, MRI, and proton MR spectroscopy (¹H-MRS). In the case of SPECT, a cerebral blood flow decrease at the time center of the temporal lobe persisted at least for more than one month. In many patients, no abnormal signs were found on MRI. Despite the presence of intracranial impairment of energy metabolism, no evidence of cerebral ischemia was obtained using ¹H-MRS at the acute and subacute stages. There were thus discrepancies between the symptoms and the findings of SPECT as well as the findings of ¹H-MRS. These data suggest that TGA may not necessarily be caused by cerebral ischemia.

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The relationship between alcohol consumption and ischemic stroke remains rather unclear. The risk of alcohol consumption and its association with stroke were examined in 338 healthy subjects, 85 cases with silent brain infarction (SBI), and 81 patients with symptomatic brain infarction (lacunar infarction, LI). The results obtained may be summarized as follows. 1) The pattern of daily drinking varied between men and women, with a larger proportion of women abstaining from alcohol among the three groups. 2) The frequency of current daily drinking habits in men amounted to 58.8% of healthy subjects, 53.9% of the patients with SBI, and 55.2% of the patients with LI. 3) The mean ethanol intake was 42.6 g/day in healthy subjects, 39.0 g/day in SBI, and 63.9 g/day in LI. 4) Heavy daily drinking of > 100 g/day of ethanol was associated with the patients with LI as compared to the healthy subjects and SBI. 5) The relation between alcohol intake and the incidence of SBI revealed a J-shaped distribution in a brain check-up study. There were no significant differences in the past history of hypertension, involving the systolic or diastolic blood pressures, between daily drinkers and lifelong abstainers among the three groups in the present study, although regular consumption of alcohol was reported to be strongly associated with hypertension. Heavy drinking consumption appeared to be related to lacunar infarction.

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Recent studies based on 24-hour blood pressure measurements in hypertensive patients have revealed that variations occur in the patterns of changes. Such variations include patients with a normal fall in nocturnal blood pressure (dippers), patients with only a slight fall in nocturnal blood pressure (non-dippers), and patients with an elevation in nocturnal blood pressure (reversed cases). Patients with abnormal blood pressure variation patterns tend to have a poorer prognosis as well as more extensive hypertensive organ disease. It is important therefore to determine how blood pressure should be controlled throughout the 24-hour period in such patients. We have observed unique blood pressure control patterns in lacunar infarct patients who were administered Nilvadipine.
We examined 35 patients with lacunar infarction who were admitted to our hospital. All patients underwent 24-hour blood pressure measurements during the period more than 4 weeks after ictus. Nilvadipine was then administered and, after 8 to 12 weeks of Nivaldipine treatment, 24-hour blood pressure measurements were recorded. The patients were subsequently divided into three groups : 13 patients with a dipple pattern, 11 with a non-dipper pattern, and 11 with a reversed pattern. Eleven of the patients with non-dipper and reversed patterns undewent cerebral blood flow measurements employing 123 IMP, SPECT before and after Nilvadipine had been given.
Following Nilvadipine treatment, the daytime and night-time blood pressure was controlled as follows. In dippers, the daytime systolic blood pressure (SBP) was significantly decreased (from 161.7±16.2 mmHg to 150±10.6 mmHg, p<0.05), while the daytime diastolic blood pressure (DBP) and night-time SBP and DBP were not significantly decreased. In non-dippers, significant decreases were noted in both the night-time SBP (from 151.4±11.2 mmHg to 135.6±8.6 mmHg, p<0.01) and night-time DBP (from 81.2±5.7 mmHg to 74.2±8.4 mmHg, p<0.05), while there were no significant decrases in the daytime SBP or DBP. In reversed cases, the night-time SBP was significantly decreased (from 165.3±16 mmHg to 147.1±14.7 mmHg, p<0.05), whereas the hight-time DBP and daytime blood pressure were not significantly decreased.
After Nivaldipine had been administered to the above-mentioned group of 11 patients including non-dippers and reversed cases, the cerebral blood flow was significantly increased from 45.9±6.1 to 49.5±7.0 (ml/100 mg/min), and the night-time blood pressure was significantly decrased. After Nivaldipine had been administered to the 11 non-dipper patients, the correlation between SBP and heart rate was improved.
The observed blood pressure control patterns can be summarized as follows : the blood pressure was decreased mainly in the daytime in dippers, and decreased mainly in the night-time in non-dippers and reversed pattern cases. It is worthy of note that the non-dipper pattern converted into a dipper pattern following Nilvadipine administration. We speculate that the central autonomic nervous function might play a role in such conversion from a non-dipper to dipper pattern. Normal function of the central autonomic nervous system was considered to have been restored. An increased cerebral blood flow and improved correlation between SBP and heart rate after Nilvadipine administration would tend to support this hypothesis.
Different blood pressure control patterns based on 24-hour variations in blood pressure were thus detected. Since the degree to which the night-time blood pressure should be controlled remains to be determined, further examinations of these variations is required.

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In order to investigate the extrinsic coagulation in the acute phase of cerebral infarction, the changes in the tissue factor (TF) and its tissue factor pathway inhibitor (TFPI) in blood drawn from a lacunar brain infarction group, an atherothrombotic brain infarction group and a cardioembolic brain infarction group were compared with those of an age-matched control group consisting of normal subjects. Samples were examined on days 1 and 7 of the acute phase of the disease using the ELISA method. In addition, the clinical relevance of the data was evaluatd by determining the changes in thrombomodulin (TM) an indicator of endothelial cell injury, and thrombin-antithrombin III complex (TAT) which reflects hypercoagulability. TF in the lacunar brain infarction group and the atherothrombotic brain infarction group exhibited significantly lower values than those in the control group on both the 1st and 7th days of the disease. TFPI, on the other hand, showed no corresponding differences. However, the TFPI in the cardioembolic brain infarction group did reveal a high value compared to that in the control group. The blood.TM in each group was within the normal range. Nevertheless, a correlation between TM and TF was evident in the atherothrombotic brain infarction group. It appeared that the changes in TF might be partially attributable to endothelial cell injury. There was no correlation between TAT and TF or TFPI. However, a correlation did exist between prothrombin time and TF in the lacunar brain infarction group. These findings could indicate that early extrinsic coagulation before the production of thrombin influenced TF in the lacunar brain infarction group. Determinations of TF and TFPI are considered important for differentiating between various disease types in the acute phase of brain infarction and for elucidating the conditions that affect coagulation.

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We investigated the superoxide dismutase (SOD) activity of the cerebrospinal fluid (CSF), results of the mini-mental state test (MMST) and radiological evaluations in 24 patients with multiple infarction. All patients were diagnosed as having multiple infarction by computed tomography (CT), and the SOD activity of the CSF was measured by the nitrite method as modified by Oyanagi. We also examined the MMST and calculated three indices of brain atrophy [the brain-atrophy index (BAI), ventricular area index (VAI), and periventricluar lucency area index (PAT)] by measuring regions of interest on CT images. The results showed that the SOD activity of the CSF was significantly correlated with the degree of brain atrophy (total SOD vs. VAT, p<0.01; Mn SOD vs. BAI, p<0.01; Cu-Zn SOD vs. VAI, p<0.02), but PAT and MMST revealed no correlation with the SOD activity of the CSF. It is concluded that the SOD activity of the CSF underwent a gradual decrease in accordance with brain atorphy in the patients with multiple infarction.

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To determine whether or not extracranial/intracranial (EC/IC) bypass surgery would benefit patients with symptomatic steno-occlusive cerebrovascular lesions and decreased cerebral blood flow, we performed a prospective randomized multi-center trial. In total, 122 patients were entered for the study, but 37 were withdrawn for various reasons including protocol violation. We therefore studied 85 patients who had suffered recent stroke or transient ischemic attacks (TIA) with atherosclerotic stenosis or occlusion of the ipsilateral internal carotid or middle cerebral artery. Thirty-five patients were randomly assigned to medical treatment with antiplatelet drugs, and 50 to EC/IC bypass surgery with the same regimen. The mean follow-up period was 29.0 months. The postoperative bypass patency rate was 96%, and the good bypass function rate was 78%. Perioperative ischemic complications were observed in 5 patients. Improvement of hemodynamic status was confirmed in 28 patients of the surgical group and 3 patients of the medical group; the difference between the two groups was statistically significant (p<0.001, chi-square test). In the surgical group, completed stroke and TIA were recorded in 6 and 5 patients, respectively, during the follow-up period included perioperative days. In the medical group completed stroke was recorded in 6 patients, and no patients experienced TIA during the follow-up period. There was no difference in incidence of ischemic stroke between the two groups. The present study failed to confirm the efficacy of EC/IC bypass surgery for preventing ischemic strokes in patients with reduced cerebral blood flow. The data may indicate that the major mechanism of ischemic stroke is embolic even in patients who have a decreased blood flow in the presence of stenosis/occlusion of the cerebral artery.

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To clarify the possible contribution of coagulation activation to the development of lacunar infarction, we measured the plasma levels of prothrombin fragment 1+2 (F₁₊₂), a molecular marker of coagulation activation, in 61 patients with symptomatic lacunar infarction (acute stage, A group, N=26, chronic stage, C group, N=35), 34 patients with asymptomatic lacunar infarction (AS group), and 67 subjects without any central nervous system symptoms and no abnormal findings on MRI (N group). The mean systolic blood pressure on admission was significantly higher in the A group than in the N group (p<0.05). The prevalence and history of hypertension was significantly higher in the A group (53.8%) and the AS group (38.2%) than in the N group (14.9%) (p<0.01 and p<0.05, respectively). There were no differences in prevalence of diabetes mellitus or hyperlipidemia among the four groups. The plasma F₁₊₂ levels were significantly higher in the A group, C group, and AS group than in the N group (p<0.05, p<0.01, and p<0.01, respectively), although there were no differences in F₁₊₂ levels among the three lacunar groups. These findings suggest that a hypercoagulable state exists in lacunar infarction with or without symptoms and may, at least in part, contribute to the development of the lacunar infarction.

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A 44-year-old man presented with short attacks of left hemiparesis. CT and MRI disclosed no abnormal ischemic lesions. Angiography revealed a web-like stenosis at the origin of the right internal caroid artery and irregular stenosis on the ipsilateral middle cerebral artery. A xenon enhanced CT study showed a decreased cerebral blood flow in the right cerebral hemisphere. The transient ischemic attacks of the patient were considered to be hemodynamic ones. Carotid endarterectomy was performed under general anesthesia without internal shunt. the septum was cut and removed with the surrounding intima of the right carotid artery. Micrographs of this specimen exhibited thickening fibrous changes of the intima. No arteriosclerotic changes were found. The diagnosis was intimal fibromuscular dysplasia (FMD). After the operation, the patient remained free from attacks. No stenosis was noted on postoper-ative angiography. Web-like stenosis is atypical among cases of FMD. The characteristics of this type of FMD are discussed.

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We recently investigated a typical case of a patient who suffered from achromatopsin. The patient was a right-handed, 73-year-old man with atrial fibrillation who suddenly lost his color vision while watching television. He has subsequently complained that “everything looks only black and white”. Both color naming and color pointing were severely disturbed, while the concept of color was completely preserved. Ordering according to brightness was also well maintained. There was no additional neuropsychological disturbance such as aphaisa, alexia or prosopagnosia. The patient with cerebral achromatopsia can thus discriminate colors according to a scaled “brightness-darkness axis”. Brain MRI revealed ischemic changes located in the bilateral occipital lobes associated with laminal cortical necrosis of the fusiform gyrus. These findings suggest that the cerebral achromatopsia demonstrated in the present patient is due to a partial defect of color perception caused by bilateral occipital lobe lesions.

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