Erythrocyte aggregation was observed in 26 cases of acute stage of cerebral infarction. For the in vivo study the blood flow of the micro-vessels of conjunctiva was observed by microscope, while the light transmission method was used for the in vitro observation of RBC-aggregation. The slowing of blood flow and marked sludging of erythrocyte are directly visualized under microscope in micro-vessels of conjunctiva in cases of cerebral infarction. The acceleration of RBC-aggregation was also shown through the in vitro measurement in cerebral infarction. The effect of Trapidil was then studied to correct this abnormal aggregation of erythrocyte. The intravenous administration of 100 mg of Trapidil decreased the degree of aggregation after 15 min of injection in “in vitro” observation. The statistically significant improvement of aggregation was also detected after four and eight weaks of oral administration of 300 mg/day of this drug. The increased aggregation of erythrocyte may cause the increase of blood viscosity, which further decreases the cerebral microcirculation. It is therefore useful to correct the disturbed hemorheological condition even in acute stage of cerebral infarction for minimizing the neurological deficits.

View full abstract

Among 179 patients with collagen diseases, 15 patients developed cerebrovascular disease (CVD). Since the incidence of CVD in systemic lupus erythematosus (SLE) was markedly higher (9/54, 16.7%) than in other collagen diseases (6/125, 4.8%), we analysed in this study the clinical characteristics of CVD in SLE in detail.
The average age of onset of CVD was 36 years old and male to female ratio was 2/7. Cerebral infarction was observed in 7 patients; cerebral hemorrhage in 1 and subarachnoid hemorrhage in 1. Hemiparesis was the most common symptom, but unusually slow progression (up to 3 weeks) was observed in one patient. Disturbances of consciousness or dizziness were often present as initial signs of neurological deficit.
Cortical lesions of parietal or temporal lobe, which were somewhat different from those in arteriosclerotic CVD, were common in CVD in SLE.
Low CSF sugar (<40 mg/dl) was detected in 4/8 patients. Proteinuria was found in 100% and, gross proteinuria (>3.5 g/day) and hypoproteinemia of nephrotic type were observed in 6/9 SLE with CVD, indicating close relationship between nephropathy in SLE and the development of CVD.

View full abstract

The effects of blood glucose levels on cerebral blood flow (CBF) autoregulation were studied in spontaneously hypertensive rats (SHR). In female SHR at the age of 5 months, blood glucose levels were varied by intravenous administration of streptozotocin (STZ) one week prior the experiment (STZ-diabetes) or intraperitoneal injections of 8% NaCl (normoglycemia), insulin + 8% NaCl (hypoglycemia) or 50% glucose (hyperglycemia) just before the study. Hydrogen clearance method was used to measure local CBF in parietal cortex, thalamus and cerebellar cortex during stepwise reduction of systemic pressure by bleeding.
Average values for mean arterial pressure (MAP) were 185 mmHg in normoglycemia, 179 in hypoglycemia, 174 in hyperglycemia and 165 in STZ-diabetes, and for blood glucose concentration were 133, 40, 465 and 337 mg/dl, respectively. Baseline CBF to cerebral cortex was greater in hypoglycemia (97 ± 17 ml/100g/min) than in normoglycemia (49 ± 4), hyperglycemia (50 ± 4) or STZ-diabetes (62 ± 9). Within each group, CBF autoregulation did not show any regional differences. In intergroup comparison, autoregulatory response in CBF in hyperglycemia and STZ-diabetes was not different from that in normoglycemia. In hypoglycemia, however, local CBF in each region was more reduced during hypotension than in normoglycemia. For example, cortical CBF was reduced to 70% of baseline CBF when MAP was decreased by only 13 ± 1% of baseline MAP in hypoglycemia, but by 37 ± 5% in normoglycemia, of its difference being significant (p<0.01).
These results suggest that either hyperglycemia or short-term diabetes does not alter CBF autoregulation, but hypoglycemia leads to impaired autoregulation. The important role of blood glucose in cerebrovascular reactivity was discussed.

View full abstract

The correlation of changes in the electroencephalography (EEG) and cerebral blood flow (CBF) in the parietal cortex and thalamus was studied during 30 minutes of bilateral carotid occlusion (BCO) and following its recirculation in spontaneously hypertensive rats (SHR). A histological examination of the brain was performed in some rats.
Thirty minutes after BCO cortical CBF was reduced from 41.8 ± 4.2 (mean ± SEM) to 4.9 ± 1.7 ml/100 g/min and thalamic CBF from 43.1 ± 2.9 to 21.6 ± 2.2 ml/100 g/min. Cortical EEG was abolished in 12 of 13 rats of which cortical CBF was reduced to 13 ml/100 g/min or below. On the other hand thalamic EEG was abolished in five rats, but in four of these rats thalamic CBF kept more than 20 ml/100 g/min. Following the recirculation, the animals having isoelectric EEG in the cortex or in the thalamus during BCO showed more marked hyperperfusion than did those with either minimal changes or incomplete abolishment of EEG. In the former, however, the improvement of the EEG was poor as compared with that of the latter. Light microscopic examination of the brain revealed mild ischemic changes in the cortex and hippocampus but not in the thalamus.
It was suggested that the CBF reduction leading to altered EEG activity might be different between in the cortex and thalamus, and that severe cortical ischemia could reduce the neuronal activities in the thalamus.

View full abstract

Xenon is an anesthetic gas in high concentration but otherwise is chemically inert, freely diffusible in brain tissue and also radiopaque by virtue of high atomic number like as iodine. Comuted tomographic measurements of CBF by stable xenon enhancement have been reported elsewhere. But the effects of xenon inhalation to CBF was contoversial. We studied the effects of 80% xenon and 20% O₂ inhalation to CBF by hydrogen clearance method in 5 unanesthetized adult cats. CBF in frontal subcortex was significantly reduced from 48.7 ± 17.4 ml/100 g/min to 36.6 ± 25.6 (-20.2 ± 7.5%) (p<0.05) and CBF in dorsal medulla also reduced by 24.2 ± 10.4% (from 36.3 ± 2.6 to 27.6 ± 20.7 ml/100 g/min) (p<0.05) by xenon inhalation for 15 minutes.
There was no difference in the changes of CBF between supuratentorial and infratentorial region. PaO₂ tended to elevate but PaCO₂, PH and blood pressure did not change significantly. Electo-encephalography showed the reduction of frequency from alph-beta rhythm to theta rhythm, but reversed to alpha rhythm within 5 minutes after the cessation of xenon inhalation.
Burst suppression or complete suppression pattern was not observed. These results indicate that reduction of CBF by 80% Xe inhalation is relatively small than that of reported before (Meyer, 1980).

View full abstract

In order to evaluate the relationship between CT and angiographic findings, especially the degree of collateral circulation estimated by 4-vessel study, 47 cases with internal carotid artery occlusion were studied by CT and angiography. The CT findings showed large infarction in 16 cases and small infarction in 24, but 7 cases had no infarction. The CT findings were classified into 7 types : combined superficial + deep type; watershed type; hemispheric type; deep type; atrophic type; and superficial type were present in 12, 10, 8, 6, 5, and 4 cases, respectively. The angiography demonstrated contralateral internal carotid stenosis in 5 cases, contralateral A₁-hypoplasia in 3 cases, and occlusio-supra-occlusionem in 6 cases, in addition to internal carotid artery occlusion (5 cases with bilateral internal carotid artery occlusion). Markedly apparent collaterals were seen; ophthalmic anastomoses (Oph.) in 30%, via the circle of Willis (CW) in 53%, and leptomeningeal anastomoses (LM) in 30%. In CW, cross-filling was seen, mainly through the anterior communicating artery in the anterior cerebral artery (ACA) and middle cerebral artery (MCA) region. LM was seen mainly as back-flow from posterior cerebral artery to ACA/MCA region. Among the various combinations of collaterals, 46% were Oph (-) + CW (_??_), + LM (-+). The size of the infarcted area generally depended on CW. But since 28% of CW (_??_) presented large infarctions of the MCA region it is likely that either an occlusio-supra-occlusionem or a propagation of secondary thrombosis from occluded site temporarily blocked the cross-filling through CW. On the other hand, in CW (-+) the combination of Oph and LM determined the size of the infarcted area. But large infarctions were seen in 36% of the Oph (+) /LM (_??_) combination, suggesting that the speed of occlusion of the internal carotid artery influenced the formation of an infarction. That is, the rapid occlusion made the infarcted area larger due to arteriolo-arteriolo anastomoses of Oph and LM.
In this study it seems difficult to conclusively make a clear correlation between the CT and angiographic findings. However, considering the pathophysiological condition, we can say that a good correlation of angiographic assessment of collateral circulation with the CT findings was present.

View full abstract

Eight patients (6 males and 2 females, mean age of 56, ranged 41 to 73 years) with idiopathic cardiomyopathy (ICM) admitted to our department because of cerebral embolism from 1979 to 1985.
In contrast, there were only 4 patients with mitral valve stenosis resulting in cerebral embolism, who admitted during the same period. Thus, ICM appears to be one of the most common heart diseases which might lead to cerebral emboli in recent years when rheumatic heart diseases extremely declined. Types of ICM were determined by echocardiography. The result was that 3 were dilated, 4 were hypertrophic and one was hypertrophic obstructive. Cerebral embolism, which has been thought to be rare, was found not uncommon in patients with obstructive ICM when associated with atrial fibrillation and/or congestive heart failure.
The characteristics of the clinical feature in stroke were as follows :
1) recurrence occurred frequently, 2) strokes began preferably at work, but occasionally at bed rest, 3) impairment of consciousness was absent or mild, and 4) prognosis was good provided no fatal complications occur in other organs, although the extent of residual symptoms was quite variable among individuals.
On CT scan, infarcts were shown in carotid system in 5 patients and vertebrobasilar system in one, and no abnormal density was found in 2 patients, in one of whom a delayed perfusion was exhibited over both systems of the affected side. Two of the 5 infarcts in the carotid territory were hemorrhagic.
Of hemostatic examinations, increases in plasma beta-thromboglobulin, platelet factor 4 and in blood viscosity were frequently observed. These results indicate that platelet activation and rheological abnormality exist, and might contribute to intracardiac thrombogenesis in ICM. Recurrence of strokes occurred in 4 of the 5 patients treated with antiplatelet agent, ticlopidine or aspirin. Thus, antiplatelet therapy appears to be less effective in stroke prevention in ICM. Instead, anticoagulant therapy should be attempted to prevent subsequent embolism in patients with ICM.

View full abstract

Somatosensory evoked potentials (SEP) were recorded in 14 patients with multi-infarct dementia (MID) as compared to 12 patients with cerebral infarction without dementia (CI) and 14 age-matched normal controls.
Patients with MID showed increased latencies of N20, P25 and N33 in comparison with controls (p<0.02, p<0.01, respectively), although there were no significant differences in the latency of N13 between these two groups.
In patients with MID, the interpeak intervals of N13 to N20 (N13-N20), N13-P25, N13-N33 and N20-N33 were significantly increased as compared to those of normals (p<0.05, p<0.05, p<0.01 and p<0.05, respectively). Furthermore, patients with MID showed significant increase in interpeak interval of N13-N33 (p<0.05) and increased tendency of N20-N33 and N20-P40 (p<0.1 and p<0.1, respectively) when compared to patients with CI.
The interhemispheric difference in peak interval of N13-N20 was significantly larger in patients with MID and CI (p<0.05 and p<0.01, respectively) in comparison with normals.
These results show that abnormalities of SEP in patients with MID were detected in both subcortical and cortical components.
In conclusion, measurements of SEP may have some value in evaluating the mental function in cerebral infarction and may be useful in differentiating MID from senile dementia of Alzheimer type, which is considered as cortical dementia and has been reported to show normal central conduction time (N13-N20) and normal latencies of both N13 and N20.

View full abstract

In 79 stroke patients admitted to our department from 1983 to 1985, the recovery of activities of daily living (ADL) was studied in relation to aging and various types of neurological impairment.
Among these types of neurological impairment, agnosia, apraxia, aphasia and intellectual decline were important factors influencing recovery of ADL. Only 37% of 27 patients with these forms of impairment were independent as regards ADL, while 98% of 52 patients without them were independent.
The outcome of patients with these impairments was very poor, especially in those who were seventy and above. Only 9% of 11 patients were independent, while 56% of 16 patients with these impairments, who were under seventy, were independent.
On the other hand, the outcome was very good in 15 patients without these impairments who were seventy and above. All of them were independent as regards ADL.
It was suggested that the following types of neurological impairment -apraxia, agnosia, aphasia and intellectual decline-were very important factors influencing recovery of ADL, especially in stroke patients of seventy and above.

View full abstract

The brain lesions responsible for palatal myoclonus have been established in many patients by autopsies, although they are yet to be demonstrated with radiological methods including X-ray CT. We report here a case of oculo-palato-skeletal myoclonus whose causative lesion was clearly delineated by MRI.
A 61-year-old man had been well until 60, when he suddenly lost consciousness followed by right hemiparesis. X-ray CT revealed a small bleeding in the tegmentum of the pons. He recovered from hemiparesis almost completely in several months. In January 1985, a year after the stroke, however, he developed abnormal involuntary movements (AIM) of the right upper and lower extremities, which gradually increased in severity. In April 1985, he was admitted to our hospital because of AIM and gait disturbance.
General physical examination was unremarkable with normal mentality and blood pressure 140/80 mmHg. On neurologic examination, the most outstanding finding was spontaneously and synchronously occurring rhythmic movements involving eyeballs and soft palates at a rate of about 2 Hz, more marked on the right. Furthermore, AIM of the right upper and lower limbs were also obvious in synchrony with rhythmic ocular and palatal movements. These AIM of the limbs were more prominent in the proximal portions and augmented with voluntary motions. They persisted while he was wakeful, disappearing in sleep. There were pyramidal tract signs, hemiataxia and hemisensory disturbance on the right as well as truncal ataxia.
X-ray CT of the brain failed to demonstrate the lesion, while MRI showed a low intensity lesion in the tegmentum of the mid- and upper pons, which extended on both sides, more dominant on the right, probably involving the right central tegmental tract; the lesion well accepted as responsible for palatal myoclonus occurring ipsilaterally.
Our case whose brain lesion causative of oculo-palato-skeletal myoclonus was successfully delineated by MRI may be very valuable, because to our knowledge there have been no reports to identify its responsible lesion roentogenologically.

View full abstract

To elucidate the pathophysiology of ischemic stroke, it is important to examine the relationship between cerebral blood flow (CBF) and metabolism during and after transient ischemia, since it is not rare to observe the spontaneous recanalization of the occluded cerebral artery on angiogram within a brief period after the ischemic attack. However, there were only a few animal experiments in which direct comparison between postischemic cerebral glucose metabolism and the sequential changes of CBF was undertaken in the same animal.
In the present study, the postischemic local cerebral glucose utilization rate (LCGU) was correlated with the sequential changes of CBF during and after transient hemispheric ischemia in mongolian gerbils under an awake condition. The hemispheric ischemia was induced by occluding the unilateral common carotid artery and maintained for 30 min. LCGU was determined between 30 and 60 min after recirculation by measns of the ¹⁴C-2-deoxyglucose autoradiographic method. CBF was measured at 20 min after CCAO and at 50 min after recirculation, respectively, with the hydrogen clearance method in the bilateral parietal cortices.
In the ischemic side of the parietal cortex, postischemic LCGU and CBF at 50 min after release of carotid occlusion was decreased and the extent of the reduction was significantly correlated with that of the reduction of CBF during ischemia. However, any relationship could not be found between LCGU and CBF during recirculation.
In the non-ischemic side, CBF during recirculation was decreased to 82% of the preischemic value. And the degree of its reduction was well correlated with the postischemic CBF in the ischemic side. In contrast to the ischemic side, there was no significant correlation between postischemic LCGU and CBF either during or following ischemia.
Above data suggest that the degree of impairment of cerebral blood flow and metabolism after transient ischemia have already been determined by the extent of damages evolved during ischemia and that reduction of CBF observed in the non-ischemic side was not always accompanied by the suppression of cerebral metabolism.

View full abstract

Our previous reports suggested that both reduction in cerebral blood flow (CBF) and acceleration of red blood cell aggregation (RBC-A) are observed in patients with occlusive cerebrovascular disease (CVD). The purpose of this study was to analyze the relationship between CBF and various data including the value of RBC-A in patients with occlusive CVD.
The subjects studied were 43 patients with supratentorial cerebral infarction. Twenty-three patients were studied in the acute stage (within 14 days after onset) and 20 in the non-acute stage (more than 21 days after onset). CBF was measured by means of the 133-Xenon intravenous injection method. The values of CBF were computed by using the initial slope index taken from 13 collimators applied to each of the diseased and non-diseased hemispheres. RBC-A in freshly obtained heparinized whole blood was estimated semi-quantitatively by using a photometric RBC aggregometer.
The relationships between CBF and various clinical and laboratory data including age, duration after onset, Ht, PaCO₂, the volume of infarction on CT, and so on were computed by means of multivariate analysis (multiple regression analysis). The areas of low density of each CT film were measured by means of a planimeter, and the volume of infarction was calculated.
The results revealed a statistically significant relationship between the value of CBF and the volume of infarction in patients in the acute stage of CVD. Significant relationships were also found between CBF and hemorheological properties including RBC-A in the non-acute stage. Accelerated RBC-A was observed in patients with reduced CBF in the non-acute stage.
Multiple regression analysis showed that in patients in the non-acute atage of occlusive CVD, one of the largest coefficients of determination among the parameters examined was that of RBC-A, followed by fibrinogen, fast blood sugar and so on.
It is concluded that the hemorheological properties including RBC-A may play a major role in determining the CBF in occlusive CVD patients in the non-acute stage, but may not do so in patients in the acute stage.

View full abstract

The mongolian gerbil is a characteristic animal in which cerebral ischemia is similar to that of the human being in that it can be induced by the ligation of the unilateral caortid artery. Howerver, although ischemia is induced in only 40 to 60 percent of the examined gerbils, there is no appropriate method to assess the development of ischemia in the living state. Recently, it has become possible to investigate the energy metabolism in sequece in a living animal by using the in vivo ³¹P-NMR method. In this study, the energy metabolism in the brain of living gerbils was investigated by measuring the in vivo ³¹P-NMR with the surface coil method, and consequently, variations in the development of ischemia in this model was detected. A unilateral carotid artery was ligated in 33 gerbils. Ishemic changes in ³¹P-NMR spectra, which consisted of a decrease in the peaks of ATP and phosphocreatine (PCr), and a concommitant increase in inorganic phosphate (Pi) associated with a decline of tissue pH, were observed on the ligated-side hemisphere in 9 of the 33 gerbils. The time required for developing these ischemic change varied from immediately after ligation to several hours after ligation. In two cases, the changes in the spectrum were transient and recovered spontaneously within 1 hour. In other gerbils, the recovery of energy metabolism was observed when circulation was restored to the ischemic brain. No ischemic changes in the spectrum were observed in 18 of the 33 gerbils. In all cases, no ischemic changes were observed in spectra obtained from the opposite-side hemisphere. However, the ischemic changes appeared immediately after ligation in all gerbils in which the bilateral carotid artery was ligated. Thus, it was apparent that in this model, there was a wide variation not only in the uncertainty of developing ischemia, but also in the time course of developing the ischemic change. In vivo ³¹P-NMR proved useful to assess the occurrence and degree of experimental cerebral ischemia in living animals.

View full abstract