The effectiveness of antiplatelet therapy has not been established in each subtype of ischemic stroke. We investigated the safety and efficacy of antiplatelet agents in the secondary prevention of lacunar and atherothrombotic stroke, and also compared vascular outcomes in treated patients in terms of pretreatment platelet aggregation test. We retrospectively compared the outcomes of 404 patients with lacunar and atherothrombotic stroke treated with or without antiplatelet agents (aspirin or ticlopidine).
In lacunar stroke, the average observation period was 39.5 months for 127 cases in the treatment group and 41.7 months for 198 cases who did not receive antiplatelet treatment (non-treatment group). There were no significant differences in baseline characteristics between the two groups. There was no significant difference in the overall cumulative event rate per 100 patient-years for recurrent ischemic stroke between the treatment group (4.3) and the non-treatment group (4.5). In the treatment group, the cumulative event rate was lower in the subgroup with accelerated platelet aggregability (1.5) compared with the subgroup with nonaccelerated platelet aggregability (6.1) with risk reduction of 75.4%, although the differences did not reach statistically significance.
In atherothrombotic stroke, the cumulative event rate per 100 patient-years for recurrent ischemic stroke was 4.3 for 31 cases with antiplatelet treatment and 7.8 for 48 cases without, with risk reduction of 44.9%.
Our results suggested that antiplatelet agents are not useful for preventing recurrent ischemic stroke in patients with lacunar stroke, but may be effective in patients with atherothrombotic stroke and some patients with lacunar stroke who have accelerated platelet aggregation.

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To clarify the etiology of periventricular hyperintensity (PVH) seen on MRI, PVH were studied in 103 patients with first-ever cerebral thrombosis (thrombosis group), compared with 2 groups of agematched controls, which consisted of 37 patients with hypertension/diabetes (risk group) and 78 patients with neither stroke nor any risk factors. MRI (T2-weighted) and angiography, examined within 3 months after the onset of stroke, were analyzed with regard to causative lesions, angiographic findings, risk factors for cerebrovascular accidents, and PVH. Causative lesions, compatible with neurological manifestations, were subdivided into 4 types; infarction involving the cerebral cortex (COR type), infarction located in the centrum semiovale (CSO type), small infarction in the internal capsule/corona radiata (IC-CR type), and infarction of brainstem/cerebellum (BS type). PVH was classified into 4 grades; none, rims/caps, patchy, and diffuse. Smooth PVH, adjoining the anterior/posterior angles and the margins of lateral ventricles, were defined as caps and rims, respectively. Irregular PVHs, confluent with each other, were defined as patchy, while diffuse PVHs extending below the cortex beyond the level of corpus callosum were defined as diffuse. Angiographic findings, obtained from 47 patients, were divided into 3 types; occlusion, stenosis (more than 75% of the lumen), and sclerotic/normal. There were 46 of the IC-CR type, 25 of the COR type, 22 of the BS type, and 10 of the CSO type. Both the COR and BS types were frequently associated with none/rims/caps PVHs, whereas diffuse PVH was seen in 60% of the CSO type and patchy PVH in 54% of the IC-CR type. On angiogram, diffuse PVH was prominent in patients with stenotic change, but none/rims/caps and patchy PHVs were accompanied by variable angiographic findings. Irregular, large PVHs (patchy and diffuse) were so frequent in the thrombosis group and hypertensive patients that these PVHs were considered to be pathologic changes due to vasculopathy. Moreover, diffuse PVH coexisted with stenotic changes and the CSO type infarction, which was caused hemodynamically by occlusive lesion of the major cerebral artery. In contrast, patchy PVH was mainly correlated with the IC-CR type infarction, which was based on the lesion of the perforating artery. These findings suggested that hemodynamic changes caused by large vessel diseases could result in diffuse PVH, while patchy PVH was confluented with multiple lesions induced by small vessel diseases.

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We divided 38 patients with cerebrovascular disease of the thalamus into 5 groups according to the site of the thalamic lesions as confirmed by X-ray CT and/or MRI. In 16 patients, we examined the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET). In the anteromedial thalamic lesion group, patients dysplayed disturbances of spontaneity, memory, reading and writing. CBF and CMRO₂ were decreased in the frontal, parietal and temporal lobes on the side of the lesion. In the dorsolateral thalamic lesion group, ataxic hemiparesis was a characteristic symptom. CBF and CMRO₂ were decreased in frontoparietal lobes on the side of the lesion. In the group with lesions confined to the nucleus ventralis posterioris thalami, the main symptoms were sensory disturbance, with cheiro-oral sensory syndrome being particularly evident. CBF and CMRO₂ were decreased in the parietal lobe on the side of the lesion. In the group with posterolateral thalamic lesions without pulvinar involvement, patients exhibited thalamic syndrome without thalamic pain. CBF and CMRO₂ were decreased in the frontoparietal and temporal lobes on the side of the lesion. In contrast, in the group with posterolateral thalamic lesions with pulvinar involvement, all patients showed thalamic pain. The decrease in CBF and CMRO₂ extended to the inferomedial region of the temporal lobe in addition to the area of decreased CBF and CMRO₂ observed in the group with posterolateral thalamic lesions without pulvinar involvement. Based on these results, we speculate that the neurological manifestations of thalamic vascular disease are associated with a decrease in cortical CBF and CMRO₂ secondary to the thalamic ledsions.

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The purpose of this study is to determine the effect of increasing ultrasonic intensity on the rate of successful recording of intracranial blood flow signals in Japanese patients in transcranial Doppler sonography (TCD). The study was performed in 163 Japanese patients using a 2 MHz range-gated pulsed-wave Doppler flowmetry. Subjects consisted of 81 males and 82 females with a mean age of 62.0 y.o. Flow signals of middle cerebral arteries were recorded by transtemporal approach at 76, 152, 228, 304, 380, 456, and 532 mW/cm². The rate of successful recording at each ultrasonic intensity was evaluated and compared each other. We also evaluated the correlation between the rate of successful recording and gender, and/or aging. Blood flow signals were recorded easily with increasing ultrasonic intensity. The rate of successful recording of flow signals was significantly improved by increasing ultrasonic intensity in both gender (43% at 76 mW/cm² vs 84% at 532 mW/cm² in male and 28% at 76 mW/cm² vs 65% at 532 mW/cm² in female). In aged female, however, only 57% of patients had clinically successful signal recording even at highest ultrasonic intensity.
In conclusion, increasing ultrasonic intensity was one of the way to improve the rate of successful recording of blood flow signals through the temporal ultrasonic windows with transcranial Doppler sonography. Increasing ultrasonic intensity alone, however, cannot completely solve the recording failure in transcranial Doppler sonography.

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To evaluate retrospectively the therapeutic usefulness of antiplatelet agents [aspirin (ASA) and ticlopidine (TP)], together with antiaggregation agents [warfarin and bucolome, which enhances the effect of warfarin], we analyzed 311 hospitalized patients (192 men aged 64.4 ± 12.9 years and 119 women aged 67.5 ± 11.1 years) suffering from initial completed strokes during the period, January 1981 to December 1984. The patients comprised 252 cases of cerebral thrombosis (154 men and 98 women) and 59 of cerebral embolism (38 men and 21 women), and were followed up for 1410.8 ± 1316.6 days in men and for 1526.5 ± 1344.6 days in women. The annual incidences of recurrence (cerebral thrombosis and embolism, TIA, RIND, cerebral homorrhage, SAH, subdural hematoma, ASO and myocardial infarction) in the patient group with cerebral thrombosis were 5.28% in the ASA group, 2.29% in the TP group, and 6.54% in the untreated control group. Statistically, recurrence was significantly lower in the TP group than in the ASA and control groups (p<0.05). In the patients with cerebral embolism, the annual incidences of recurrence were 11.16% in the ASA group. 19.31% in the TP group, 4.13% in the warfarin group, 0% in the warfarin plus bucolome group, and 24.88% in the control group. Comparative analysis among the antiplatelet (ASA, TP, and ASA plus TP) group, antiaggregation (warfarin, and warfarin plus bucolome) group and controls demonstrated that recurrence was significantly lower in the antiaggregation group than in the antiplatelet group and the controls (p<0.01). The difference between the antiplatelet group and the controls was not statistically significant. Cerebral hemorrhage occurred in 5 patients : one man each in the ASA group and the TP group, one woman in the antiaggregation group, and one man and one woman in the controls. Administration of antiplatelet or antiaggregation agents displayed no definite and serious side effects. In conclusion, a clinical efficacy in preventing secondary cerebral thrombosis was noted for TP, but not for ASA, while warfarin or warfarin plus bucolome was effective in preventing secondary cerebral embolism.

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This study was undertaken to evaluate the possible changes in the subunit composition of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type glutamate receptor (GluR) in the hippocampal CA1 neurons which are vulnerable to ischemic insult. Cerebral ischemia was produced transiently by occluding both carotid arteries of Mongolian gerbils for 5 min. In situ hybridization histochemistry with oligonucleotide probes for GluR1-4 mRNAs and immunocytochemistry for either GluR1, the combination of GluR2 and G1uR3 (GluR2/3), or GluR4 were performed at 1 and 3 days after ischemia. Sham-operated animals had high levels of expression of mRNAs encoding G1uR1-3 throughout the hippocampus, while they had low levels of expression of GluR4 in the CA1-3 neurons. After 1 day of recirculation, the levels of G1uR1 and GluR3 mRNAs decreased dramatically in the CA1 neurons, and was no longer detectable at 3 days after the ischemic insult. In contrast, GluR2 mRNA showed only a slight decrease at day 1, and had decreased even further at 3 days. The levels of G1uR4 mRNA, which were observed mainly in the interneurons, changed very little during the entire recirculation period. The immunocytochemical study revealed that GluR1 and GluR2/3 proteins were distributed evenly along the apical dendrites in sham-operated gerbils. By 1 day after the ischemic insult, these immunoreactivities were still observed, but appeared to be localized in certain areas such as the postsynaptic membranes. No detectable G1uR1 or GluR2/3 immunoreactivity was moted at 3 days after the ischemic injury, although GluR4 was observed in the cells like interneurons which were resistant to ischemic insult such as the interneurons. The present results indicated that GluR2 mRNA was expressed more stably than that of either GluR1 or GluR3 in the CA1 pyramidal neurons during the early reperfusion period after a transient ischemic insult. This specific downregulation of receptor subunits in the CA1 neuron Suggests that the subunit composition of the AMPA receptors may be altered by ischemia. Since the Ca²⁺ permeability of the AMPA receptor is determined by its subunit composition and since the heteromeric receptors containing the GluR2 subunit are Ca²⁺-impermeable, the stable expression of GluR2 could protect the cells by decreasing Ca²⁺ influx into the CA1 cells, although this meeds to be confirmed by immunocytochemistry using an anti-GluR2 specific antibody. Our deta also imply that the difference in the vulnerability to ischemia between the pyramidal neurons and the interneurons may be due to coexpression of the GluR4 subunit.

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Thirty patients with infarction of the basis pontis were clinically evaluated in order to determine the clinical characteristics of the infarction resulting from occlusion of the mouth of the paramedian basilar branches (branch occlusion). Based on the MRI findings, the patients were divided into a B-group (branch occlusion) and an L-group (lacunar infarction). The B-group was defined as having infarcts confined to the territory of a single basilar paramedian branch and extending to the pontine basal surface, while the L-group had small (less than 15 mm) lesions isolated within the parenchyma. In the B-group, initial confusion was noted in 47% of the patients. All patients had dysarthria and hemiparesis. Progressive deterioration was observed in 80% of the patients. One third of the patients had a relatively poor outcome (moderate hemiparesis, dependent activities of daily life). In the L-group, all patients had a clear consciousness and classic lacunar syndrome. Progressive deterioration was rare (27% of the patients). All patients achieved a good outcome (independent activities of daily life). Comparing the risk factors, diabetes mellitus and hyperlipidemia were more common in the B-group than in the L-group. The differences between the two groups may reflect the size of the lesions and the pace and tempo of ischemia. It appeared that most cases of the B-group have branch athermatous disease.

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To examine the involvement of manganese superoxide dismutase (MnSOD) in the acquisition of ischemic tolerance by CAI neurons, we performed in situ hybridization histochemistry and immunocyto-chemistry for MnSOD in gerbil hippocampus following lethal or non-lethal transient cerebral ischemia to the hippocampal CA1 neurons. We produced transient global cerebral ischemia by occluding the common carotid artery bilaterally. The animals were divided into three groups : 1) a single 5-min ischemic insult group, 2) a single 2-min ischemic insult group, and 3) a repeated ischemic insult group with underwent a 5-min period of ischemia 2 days after a single 2-min period of ischemia. Histochemical examination revealed a transient increase in the expression of MnSOD mRNA without expression of MnSOD protein in CA1 pyramidal neurons following 5 min of ischemia. However, at 3 days of ischemia, MnSOD mRNA as well as its protein was expressed in the glial cells such as microglia which proliferated in the white matter region of CAl. On the contrary, both MnSOD mRNA and protein were expressed in the CAl pyramidal neurons by 1 day after non-lethal 2 min of ischemia. This expression was lasting during 7-day recirculation following the ischemia. Little MnSOD expression was noted in the reactive microglia. Repeated ischemia demonstrated a subtle change in MnSOD protein expression as compared to that expressed before the Last ischemic insult. Lethal ischemia causing delayed neuronal death in the CAl is associated with the loss of MnSOD, while non-lethal ischemia inducing ischemic tolerance by the CAl neurons is associated with the increase of MnSOD. These results suggested that MnSOD in the neurons has an important role in the cell defense mechanism against oxidative stress.

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The antithrombotic effects of drugs have rarely been evaluated in experimental animals because of a lack of adequate models. We recently reported a method for inducing endothelial damage in the gerbil common carotid artery, which led to platelet thrombus formation at the site of endothelial injury with a high reproducibility. We evaluated the antithrombotic effects of ibudilast, a cerebral vasodilator with actions potentiating prostacycline (PGI₂) activity and aspirin employing this method. In 40 adult male gerbils, a unilateral common carotid artery was squeezed for 2 min employing a device prepared for this purpose to induce endothelial damage. Thrombus formation was subsequently estimated with a microscope for 30 min. 2 mg/kg aspirin, 0.3 mg/kg or 1.0 mg/kg ibudilast, or normal saline as a control was injected intravenously at 10 min prion to the endothelial injury. In control group 70% of animals developed a white thrombus at the site of endothelial injury. 2 mg/kg aspirin significantly reduced the frequency of thrombus formation (10%, p<0.05). 1.0 mg/kg ibudilast reduced the frequency of thrombus formation to the same extent as aspirin (10%, p<0.05), although 0.3 mg/kg ibudilast failed to decrease the thrombus formation (20%, p<0.1). The antiplatelet action of ibudilast was shown to be feeble as compared with that of aspirin, when tested ex vivo. However, the ex vivo evaluation may not accurately reflect the antiplatelet action of drugs which influence the PGI₂activity, since PGI₂is produced mainly in the endothelium. The present in vivo method appears to be useful for assessing the antiplatelet actions of such drug.

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We report route finding defect in 2 patients with subcortical hemorrhage. In one patient, the hemorrhage involved in the right medial parieto-ocipital lobe including the retrosplenial region. In the patient with hemorrhage in the right posterior inferior temporal lobe, SPECT showed hypoperfusion in that region extending to the right parieto-occipital lobe. Both patients displayed topographical disturbance, mild visuoconstructive disability and transient metamorphopsia during their acute phase of illness. They could recognize landmarks (streets and familiar houses, etc.), but failed to recognize the relative positions of landmarks, indicating that their topographical distrubance was a route finding defect due to perceptual distrubance and or memory disturbance of the relative positions of landmarks.<BE>
We presumed that their defective route finding may have been caused by the medial parieto-occipital and retrosplenial lesions.
A careful differentiation between route finding defect (disturbance of recognition or memory for the relative positions of landmarks) and agnosis for streets and houses (disturbance in the recognition of landmarks) should be made in the evaluation of topographical disturbances.

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A 77-year-old woman experienced vertigo when she stood up at midnight. Duplex ultrasonography and digital subtraction antiography revealed severe stenosis (70%) at the proximal portion of the right internal carotid artery. Ambulatory blood pressure monitoring demonstrated a significant fall in blood pressure during the night. In spite of the carotid lesion, cerebral blood flow (CBF), oxygen extraction fraction and cerebral metabolic rate for oxygen (CMRO₂), as determined by positron emission tomography (PET), were all within normal limits. Thus, the administration of ticlopidine (100 mg/day) was started. However, two weeks after the PET study, she developed extensive borderzone infarction in the right cerebral hemisphere, which most likely resulted from a hemodynamic catastrophe. The second PET study demonstrated a decrease in CBF with a matched reduction in CMRO₂ in the affected cerebral hemisphere. This case suggests the limitation of PET in the prediction of prognosis in patients with severe stenotic lesions in major cerebral artereis.

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A 59 year-old man with a history of hypertension was admitted to our neurological service for-left sided weakness and gait disturbance. Initial neurological examinations at admission revealed left-sided hemiparesis, involving the face, without dysarthria. High resolution magnetic resonance imaging demonstrated a high signal intensity localized in the lateral two-thirds of the right cerebral peduncle on T₂ weighted images on 5th day after onset. There was no obvious occlusion of the right posterior cerebral artery or basilar artery in selective vertebrobasilar angiography. The localized infarction of the right cerebral peduncle could be attributable to lacunar infarction in the territory of the peduncular perforating arteries from the right posterior cerebral artery.

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Paradoxical cerebral air embolism is an unusual complication, usually associated with penetrating trauma to the thorax, percutaneous thin needle biopsy of the lungs, or decompression sickness. We report two patients with paradoxical cerebral air embolism complicating accidental disconnection of a sub-clavian intravenous catheter.
Patient 1 was an 85-year-old man with tongue caner. He had been under hyperalimentation and developed dyspnea and became unresponsive to verbal stimulation after he tore off his subclavian intravenous catheter. He had repeated tonic convulsions and computerized tomographic (CT) scanning performed 2 hours lafter revealed multiple small, well defined air collections within the right frontal lobe. On magnetic resonance imaging (MRI) performed three days later, there were well defined areas of infarction scattered through the right frontal, and parietal lobes and the right basal ganglia. His condition deteriorated with complicating pneumonia and he died 2 months later. Autopsy disclosed that the foramen ovale was closed and there were no right-to-left shunts in either the heart or lungs. Patient 2 was a 76-year-old woman admitted for radiation therapy of malignant lymphoma. She had an alimentation catheter inserted and developed dyspnea, tachypnea and became unresponsive after she tore it off. CT scanning performed one hour later revealed multiple linear air collections, presumably located within small-caliber arteries, in the right frontal lobe. MRI taken next day showed infarction within the right frontal and parietal lobes.
The mechanism of paradoxical cerebral air embolism is unclear, but the pathologic findings of our first patient suggest that air in the pulmonary circulation passes through a physiologically closed but anatomically patent arterior-venous small shunt within the lung. We also conclude that CT scanning provides the most direct method for confirming the diagnosis of cerebral air embolism and MRI is useful for the early discrimination of cerbral infarction areas.

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