Allthough progress is being made in treatment of acute ischemic stroke to reduce the size of the cerebral infarct and thereby lessen the severity of the neurologic deficit, it seems likely that prevention holds the key to reducing death and disability from stroke. Prevention requires the major stroke precursors to be identified, these include risk factors; increasing blood pressure level, diabetes, cigarette smoking, low levels of physical activity, increased fibrinogen level; positive family history of stroke, extremes of alcohol consumption; left ventricular enlargement either left ventricular hypertrophy by ECG (or preferably left ventricular mass by echocardiography), as well as predisposing diseases; coronary heart disease, cardiac failure, and atrial fibrillation. Other cardiac abnormalities, increased left atrial size and mitral annular calcification have also been implicated. High total cholesterol or low HDL-cholesterol has not been consistently related to ischemic stroke, while low levels of total cholesterol have been related to intracerebral hemorrhage.
Clinical trials have provided evidence that reducing blood pressure, systolic as well as diastolic, reduces stroke incidence and that warfarin anti-coagulation prevents stroke in atrial fibrillation. Recent trials of rigid control of blood sugar in insulin dependent diabetics suggest that vascular complications may also be prevented by improved management. Observational data strongly support cessation of cigarette smoking and promotion of moderate physical activity as a means of significant stroke reduction. Recent trials of HMG CoA reductase inhibitors for cholesterol reduction have disclosed a striking reduction in cardiovascular events including stroke perhaps via an effect of these drugs on plaque rupture, lesion activation and endothelial dysfunction. Elevated plasma homocysteine levels, amenable to reduction with vitamins particularly folic acid, have also recently been implicated.
Identification of persons at increased risk, accounting for the cumulative effect of multiple risk factor abnormalities, is key to stroke prevention. A Framingham stroke risk profile identifies those at high risk and provides each individual's conditional probability of stroke. These high risk individuals can thus be alerted so effective preventive measures may be instituted.

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Computed tomography often demonstrates a well-demarcated low density area which is encountered around high density lesions in cases of acute intracerebral hematoma. This region on magnetic resonance imaging (T₁-weithted images) was observed as a well-demarcated low intensity area. When we performed stereotactic aspiration the low density area disappeared or decreased in volume after initial aspiration of the hematoma. The level of fibrin degradation products (FDP) in the aspirated hematoma was extremely high. These findings suggest that the low density area may consist of serous components as a result of blood clot retraction. We named this kinds of feature on computed tomography as a “double density hematoma”. This region should be considered as a poriton of the intracerebral hematoma.

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Recent descriptions of the identification of the vasoconstrictor peptide, endothelin-1 (ET-1), and inflammatory interleukin-6 (IL-6) have attracted much attention and excited speculation regarding their possible pathological significance in cerebral infarction. The present study focused on the expression of ET-1 and IL-6 in the human stroke brain in relation to the healing process of occlusive cerebrovascular disease. Eight patients with occlusive cerebrovascular disease were employed. For immunohistochemical studies on ET-1 and IL-6, polyclonal anti-human ET-1 antibody (Peptide Institute Inc., Japan) and polyclonal rabit antibody against human IL-6 (Genzyme, Boston) were used, respectively. In the stroke brain at the chronic phase of cerebrovascular accident, the immunohistochemical method demonstrated simultaneous production of both ET-1 and IL-6 associated with astrocyte proliferation in serial sections derived from the boundary area. In addition, the endothelial cells demonstrated strong staining for ET-1 as well as for IL-6. The percentages of ET-1 expression in the astrocytes and endothelium were 87.6 ± 12.8% and 93.2 ± 7.8%, respectively. IL-6 also exhibited simultaneous expression in both the astrocytes (92.9 ± 5.4%) and endothelium (90.0 ± 9.9%). ET-1 and IL-6 can thus be produced by both astrocytes and endothelium, and act on them in intercellular reactions. The presence of IL-6 immunoreactivity in the infarcted area is functionally linked with ET-1. Our data indicate that, although the precise order remains unknown, a sequence of immunologic events may play a role in the pathophysiology of human stroke.

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Reversed sleep-waking (S-W) rhythm which involves drowsiness in the daytime and waking at night, occasionally accompanied by restless confusion, is frequently encountered in the early stages of stroke and is one of the important factors to be considered in the management of stroke patients. The purpose of the present study was to examine the characteristics of such reversed S-W rhythm and how to treat it. The subjects comprised 147 patients who were admitted on the day of onset of stroke. Of these patients, 97 had cerebral infarction, while the remaining 51 had intracerebral hemorrhage. The level of consciousness on admission was evaluated according to the Japan coma scale.
The findings obtained may be summarized as follows :
1) A reversed S-W rhythm was observed in 43 patients (29.3%) and was frequent in patients older than 70 years of age who displayed impairment of consciousness on admission [p<0.001; χ^a test].
2) Among the 18 patients without consciousness impairment on admission who display initial symptoms of reversed S-W rhythm within 2 or 3 days after the onset of stroke 15 (83.3%) showed these symptoms on the day of onset of stroke. Of the patients with consciousness impairment on admission, 23 (92.0%) displayed initial symptoms of reversed S-W rhythm within 3 days after arousal.
3) Concerning the patients with cerebral infarction, a reversed S-W rhythm was noted in 14 (51.9%) of the 27 patients with infarction of the cortical artery of the MCA and occlusion of the ICA-MCA trunk. Concerning the patients with intracerebral hemorrhage, a reversed S-W rhythm was noted in 12 (70.6%) of the 17 patients with type IV-V on CT grading of putaminal hemorrhage, type III on CT grading of thalamic hemorrhage, intracerebellar and brainstem hemorhage. Thus, a reversed S-W rhythm was frequently observed in patients with severe types of cerebral infarction and intracerebral hemorrhage [p<0.001; χ² test].
4) It was evident that a nonactive body position was closely related to the reversed S-W rhythm, since 41 patients developed the symptoms while in a passive sitting position or supine position.
5) As initial symptoms of the reversed S-W rhythm, waking at night was seen in 28 patients and drowsiness in the daytime in 15 patients. Mental symptoms were observed in 16 patients (37.2%) of this total with a reversed S-W rhythm.
6) When a reversed S-W rhythm was diagnosed, sleep in the daytime was noted in 23 patients, sleep in the daytime and waking at night in 17 patients, and waking for the whole day in 3 patients. Mental symptoms were observed in 26 patients (60.5%) of this total.
7) To treat the reversed S-W rhythm, active management in the sitting position during the daytime rehailitation therapy, and administration of Tiaprid Hydrochloride and minor tranquilizers were found to be effective.
For the treatment of reversed S-W rhythm, it is thus useful to identify the initial symptoms early and to give the patients Tiaprid Hydrochloride at the time of going to sleep along with active management in the sitting position and rehabilitation therapy during the daytime.

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We investigated the efficacy of drugs used to treat brain edema in a rat acute cerebral infarction model by MRI image analysis. Twenty-six Sprague-Dawley rats were anesthetized with halothane, and the right middle cerebral artery was permanently occluded via a transvascular approach using a nylon 2-0 suture. At 24 hours after the occlusion, axial T₂-weighted MRI images were taken before and 2 hours after intraperitoneal administration of a test drug. After the administration of 1.7 g/kg glycerol (n=9), 3.3 g/ kg mannitol (n=9) or 17 mg/kg furosemide (n=8), the high intensity area (HIA) in the whole brain amounted to 92% (p<0.01), 94% (p=0.07), or 95% (p=0.03), respectively as compared to the corresponding HIA before administration. The HIA in the cerebral cortex amounted to 87% (p<0.01), 89% (p=0.03), or 98% (p=0.47), and that in the striatum to 102%, 106%, or 87% (p<0.05), respectively. The signal intensity change (before →aftre) was 54→49 (p<0.01), 54→50 (p<0.01), or 55→54 in the left side normal cortex; 102→97 (p<0.01), 100→98, or 98→97 in the injured side cortex; and 100→93 (p<0.01), 94→88 (p=0.03), or 94→94 in the injured side striatum, respectively. Improvement of edema by the drugs was observed as a reduction in HIA and a decrease in signal intensity on MRI, and the changes were significant in the case of administration of each of glycerol, mannitol and furosemide.

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This paper described the findings obtained in 4 cases of unilateral occlusion of the internal carotid artery, in which differences in diameter of the middle cerebral artery (MCA) were demonstrated by three-dimensional CT angiography (3D-CTA) between the occluded and non-occluded side. The main angiographic collateralization was Willisian in 2 cases, and ophthalmic in the other 2 cases. However, the collateral circulation was poor as seen on angiograms, and cerebral infarctions were detected at the borderzone area by CT scans in all of the 4 cases. The mean maximal diameter of the horizontal portion of the MCA on the occluded side was 2.5 mm, which was significantly smaller than that of the non-occluded side (3.9 mm; p<0.05) or of control subjects (3.4 mm). The mean cerebral blood flow in the MCA territories on the occluded side was about 16 ml/100 g/min as measured by xenon-CT, and the mean flow velocity in the horizontal portion of the MCA was 13 cm/sec as determined with a 2 MHz pulsed transcranial doppler velocimeter. These data suggest the presence of severely dysfunctioned cerebral hemodynamics. The clinical significance of the existence of laterality in the diameter of the MCA on 3 D-CTA is discussed in relation to the detection of abnormal cerebral hemodynamics.

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The time of onset of stroke was investigated in 1, 248 patients with stroke admitted to our hospital between April 1988 and December 1993, including 434 patients with brain hemorrhage and 814 with brain infarction. The brain infarction was classified according to the clinical category : atherothrombotic stroke (n=325), cardioembolic stroke (n =214), lacunar stroke (n=225), and others (n=50). The time of onset of stroke was judged by questioning the patient or a person who observed the onset. For all types of stroke, there was a significant diurnal variation showing two peaks : one during the morning, and the other during the evening. For brain hemorrhage, there were two peaks with a high incidence of stroke during 0800-1000 a.m. and during 1800-2000 p.m., and the incidence of stroke was low during the night (chi-square test for goodness of fit, p<0.001). Patients often noticed their symptoms on awakening : in 34% of atherothrombotic stroke, and in 39% of lacunar stroke. In addition, there was a smaller peak in the incidence of onset among patients with atherothrombotic stroke and lacunar stroke during 1600-1800 p.m. (p<0.001). Patients with cardioembolic stroke also exhibited peak onset times of early to mid-morning and early evening, and a low onset time during dawn (p<0.001). Our data suggest a broadly similar peak onset time for different types of stroke. This might be due to some common mechanism for the onset of all types of stroke.

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We attempted to clarify the clinical features and mechanisms of infarction which is limited to the middle cerebellar peduncle. Over the course of about 9 years, 19 patients with anterior inferior cerebellar artery (AICA) territory infarction diagnosed by magneric resonance imaging (MRI) were admitted to our hospital. Among these 18 patients, MRI demonstrated ischemic lesions limited to the middle cerebellar peduncle in 7 patients (1 bilateral case, 6 unilateral cases; 3 males, 4 females; age range, 52-76 years old; average age, 66.3 years old). We assessed the risk factors, mechanisms, neurological characteristics, angiograms (6 cases), auditory brainstem responses (ABRs; 2 cases), and prognosis. As risk factors, byperlipidemia (6 cases), hypertension (5 cases), a history of cerebrovascular disease (4 cases), diabetes mellitus (3 cases), smoking (2 cases), and heart disease (1 case) were identified. The infarcr was thrombotic in all of the 7 patients. Cerebellar ataxia (gait instability, limb ataxia, and dysarthria) was observed in all of the 7 cases. Vertigo (4 cases) and hearing impairment (1 cases) were also encountered. However, cerebellar ataxia (gait instability, limb ataxia, and dysarthria) only was noted in 3 out of the 7 patients. Lesions of the vertebrobasilar system were detected in 4 out of the 6 patients who underwent cerebral angiography. ABRs were recorded in 2 patients, and abnormal responses were found in both of them. Their prognosis was relatively excellent. All patients were ambulatory at the time of 3 months after onset, althought mild or moderate residual deficits were present. We posturlate that a watershed infarction caused by large-artery occlusive disease resulted in infarctions limited to the middle cerebellar peduncle.

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We consider that the vulnerable and selective death of hippocampal CA1 neurons caused by short cessation of the brain circulation, might act like a fuse system in an electrical circuit, to save the whole brain and life from further ischemic insult. To test this hypothesis, we examined whether or not preconditioning by 5 min forebrain ischemia, which causes hippocampal CA1 neuronal death, could reduce the neuronal damage in other brain regions and decrease the mortality rate following 15 min forebrain ischemia in the gerbil. Male Mongolian gerbils were given either a single insult of 15 min forebrain ischemia by occlusion of the bilateral common carotid arteries (15 min group, n=61) or a double ischemic insult, i.e., 5 mm forebrain ischemia followed by 15 min forebrain ischemia 10 days later (5-15 min group, n=40). Gerbils were observed for 14 days after the last ischemic insult. 40% of the gerbils in the 15 min group survived, whereas significantly more gerbils (65%) in the 5-15 min group survived (p<0.05, Kaplan-Meier method). Furthermore, the 5-15 min group demonstrated a significantly reduced body weight loss after the last ischemic insult, as compared to the single insulted group (p<0.005). However, pathological analysis of brain tissues from 14-day survivors revealed that neuronal death in the surface layer of the cortex was more severe in the 5-15 min group than in the 15 min group, and severe neuronal death was present in the hippocampal CA3 region and the subiculum to the same extent. The present data indicate that preconditioning by 5 min forebrain ischemia can attenuate the mortality rate and body weight loss after 15 min forebrain ischemia. However, the potential protective role afforded by 5 min ischemia requires further detailed investigation.

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We report the case of an 83-year-old right-handed woman who had neuropsychological disturbances compatible with a right-hemispheric lesion after a massive left-hemispheric infarction. She developed right hemiplegia, right sensory disturbance, right unilateral spatial neglect, anosogonsia, motor impersistence and left neck rotation. Her spontaneous speech, comprehension and repectition were normal. Brain CT and MRI revealed a massive infarction in the whole area of the left middle cerebral artery territory and partial area of the left anterior cerebral artery territory. The patient was right-handed, but she had severe and persistent neucopsychological disturbances compatible with a right-hemispheric lesion without aphasia. She represents a very rare case of reversed lateralization in which the cerebral lateralization of hemispheric functions was reversed.

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A 37-year-old man noted thermohypoesthesia of his right arm and chest, followed by dysphagia, nausea and unsteady gait. Five days later, neurological examinations revealed left limb ataxia, truncal instability with a tendency to lean to the right, hypalgesia and thermohypoesthesia on the right side of the region between the levels C2 to Th12. MRI on the 14th day disclosed a high intensity lesion on T₁- and T₂-weighted images and a mixed signal intensity lesion on the T₂-weighted image in the left lateral medulla oblongata. Cerebral angiography demonstrated no abnormality. It was inferred that the segmental dissociated sensory disturbance with facial sparing had been caused by partial involvement of the lateral spinothalamic tract which is somatotopically arranged with the fibers from the sacral segments most lateral. There were no risk factors for cerebral bleeding. We consider that the etiology of this hematoma may have been a crytpic vascular malformation.

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