Tsuyoshi Omae

Hemorrhagic transformation in cerebral embolism

We studied the mechanism of hemorrhagic infarction after acute cerebral embolism in 160 patients by brain computed tomography and angiography. Hemorrhagic infarction during the month after the embolic event was evident in 65 patients (40.6%). Initial angiography a median of 1.5 (range 1-60) days after the event revealed occlusion of the cerebral arteries in 117 of 142 patients (82.4%), and reopening of the vessels was observed in 56 (94.9%) of 59 patients who had follow-up angiography a median of 20 (range 3-47) days after the event. The incidence of hemorrhagic infarction was higher in patients greater than or equal to 70 years old (31 of 61, 50.8%) than in those aged 50-69 years (27 of 72, 37.5%) or less than 50 years (seven of 27, 25.9%) (greater than or equal to 70 vs. less than 50, p less than 0.05). In patients with moderate or large infarcts, hemorrhagic infarction developed in 50.0% or 51.5%, respectively, while in those with small infarcts it developed in only 2.9% (p less than 0.05). No correlation was found between hemorrhagic infarction and history of hypertension or blood pressure during the acute stage of stroke. Thrombolytic and/or anticoagulant therapy did not affect the incidence of hemorrhagic infarction (40.0% with vs. 40.7% without therapy) but tended to cause massive hematoma. Our results indicate that hemorrhagic transformation in cerebral embolism is caused not only by reopening of the occluded vessels but also by other factors such as age and size of the infarct. Hypertension per se seems to be less important for hemorrhagic infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient and Permanent Resolution of Ischemic Lesions on Diffusion-Weighted Imaging After Brief Periods of Focal Ischemia in Rats Correlation With Histopathology

BACKGROUND AND PURPOSE The early ischemic lesions demonstrated by diffusion-weighted imaging (DWI) are potentially reversible. The purposes of this study were to determine whether resolution of initial DWI lesions is transient or permanent after different brief periods of focal brain ischemia and to evaluate histological outcomes. METHODS Sixteen rats were subjected to 10 minutes (n=7) or 30 minutes (n=7) of temporary middle cerebral artery occlusion or sham operation (n=2). DWI, perfusion-weighted imaging (PWI), and T(2)-weighted imaging (T(2)WI) were performed during occlusion; immediately after reperfusion; and at 0.5, 1.0, 1.5, 12, 24, 48, and 72 hours after reperfusion. After the last MRI study, the brains were fixed, sectioned, stained with hematoxylin and eosin, and evaluated for neuronal necrosis. RESULTS No MRI or histological abnormalities were observed in the sham-operated rats. In both the 10-minute and 30-minute groups, the perfusion deficits and DWI hyperintensities that occurred during occlusion disappeared shortly after reperfusion. The DWI, PWI, and T(2)WI results remained normal thereafter in the 10-minute group, whereas secondary DWI hyperintensity and T(2)WI abnormalities developed at the 12-hour observation point in the 30-minute group. Histological examinations demonstrated neuronal necrosis in both groups, but the number of necrotic neurons was significantly higher in the 30-minute group (95+/-4%) than in the 10-minute group (17+/-10%, P<0.0001). CONCLUSIONS Transient or permanent resolution of initial DWI lesions depends on the duration of ischemia. Transient resolution of DWI lesions is associated with widespread neuronal necrosis; moreover, permanent resolution of DWI lesions does not necessarily indicate complete salvage of brain tissue from ischemic injury.

Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan.

The incidence of cerebral amyloid angiopathy in a general population was evaluated in brains of 400 consecutive autopsies of residents of Hisayama, Japan (November 1971-October 1983). Six samples taken from frontal lobe, parietal lobe, temporal lobe, occipital lobe, hippocampus, and basal ganglia of the same side of each brain were stained with both hematoxylin and eosin and Congo red. The specimens were surveyed microscopically with polarized light for deposition of amyloid in the vascular wall. In 26 cases with brain hemorrhage, the region surrounding the hemorrhagic sites was further examined to study the probable causal relation between cerebral amyloid angiopathy and brain hemorrhage. Cerebral amyloid angiopathy was found in 40 of 218 men (18.3%) and 51 of 182 women (28.0%). The incidence increased with age in both sexes. The frontal lobe was most frequently affected (66 cases), followed by parietal lobe (65), occipital lobe (49), temporal lobe (44), and hippocampus (32); the putamen was never affected. The incidence of cerebral amyloid angiopathy did not correlate with blood pressure or with the severity of cerebral atherosclerosis. Among the 26 cases in which there was brain hemorrhage, only one cerebellar hemorrhage, in an 85-year-old man, was attributed to cerebral amyloid angiopathy. This case showed four microaneurysms in vessels, with cerebral amyloid angiopathy surrounding the hemorrhagic site. Thirty similar lesions were observed in eight cases without brain hemorrhage. Cerebral amyloid angiopathy may play an etiologic role in the development of brain hemorrhage through formation of angionecrosis and microaneurysm.

Spontaneous hyperthermia and its mechanism in the intraluminal suture middle cerebral artery occlusion model of rats

BACKGROUND AND PURPOSE The intraluminal suture middle cerebral artery occlusion (MCAO) model is increasingly used in experimental stroke studies. The purposes of this study were to determine whether (1) spontaneous hyperthermia occurs after different periods of MCAO in this model, (2) hypothalamic injury contributes to hyperthermia, and (3) hyperthermia increases infarct volume after permanent MCAO. METHODS Rats were subjected to 60, 90, and 120 minutes of transient MCAO (n=8 per group), permanent MCAO (n=8 per group, 5 groups), and permanent hypothalamic occlusion, in which an occluder was inserted 15 to 15.5 mm to block only the hypothalamic branch from the internal carotid artery (n=4) with the use of the intraluminal suture MCAO method. In one group undergoing permanent MCAO, the body temperature was maintained at 37 degrees C throughout the experiment. In another group (n=4) undergoing 90 minutes of temporary MCAO, diffusion- and perfusion-weighted imaging were performed to document the in vivo ischemic changes in the hypothalamus. Body temperature was measured hourly for 12 hours. At 24 hours (12 hours in 2 permanent MCAO groups), triphenyltetrazolium chloride staining was used to verify ischemic hypothalamic injury and to calculate corrected infarct volumes. RESULTS Spontaneous hyperthermia (>39 degrees C) occurred in the 120-minute group, all permanent MCAO groups, and the hypothalamic occlusion group but not in the 60-minute or the 90-minute groups. Hypothalamic infarction was found in 1 rat each in the 60-minute and 90-minute groups, 6 of the 8 rats in the 120-minute group, 37 of the 40 rats in the permanent occlusion groups, and all 4 rats in the hypothalamic occlusion group. After 90 minutes of transient MCAO, the decreased cerebral blood flow and apparent diffusion coefficient values in the hypothalamic region during occlusion recovered fully 2 hours after reperfusion. The corrected infarct volumes were identical in all permanent occlusion groups. CONCLUSIONS The intraluminal suture MCAO lasting for >/=2 hours induces spontaneous hyperthermia that is associated with hypothalamic injury, and delayed spontaneous hyperthermia does not increase infarct volume after permanent intraluminal suture MCAO.

Incidence and prognosis of subarachnoid hemorrhage in a Japanese rural community.

Twenty-six first episodes of subarachnoid hemorrhage occurred among 1,621 Hisayama residents aged greater than or equal to 40 years during the 22-year follow-up of a prospective study. Subarachnoid hemorrhage was confirmed by both clinical and autopsy findings. The average annual incidence (96.1/100,000 population) was 3-13 times higher than any previously reported and steeply increased with age in both sexes, being 2.3 times higher for women than for men after adjusting for age. Nine patients (35%) died less than or equal to 8 hours after the onset of subarachnoid hemorrhage. None was correctly diagnosed on the death certificates, and four of the nine (44%) were misdiagnosed as intracerebral hemorrhage. We found the survival rate of patients suffering subarachnoid hemorrhage to be much lower than previously reported because we detected a large number of sudden deaths due to subarachnoid hemorrhage through the high rate of autopsy in our cohort (81.4%).

Intracerebral hemorrhage in a Japanese community, Hisayama: incidence, changing pattern during long-term follow-up, and related factors.

The incidence of intracerebral hemorrhage over 13 years is compared between two Hisayama cohorts. Among men aged 40 years or older, the annual incidence declined significantly from 3.1/1,000 in the early cohort (1961-1970) to 1.2/1,000 in the recent cohort (1974-1983). Massive ganglionic hemorrhage decreased, while small or medium-sized intracerebral hemorrhage increased in the recent cohort on pathologic or computed tomographic examination. These trends could be due to the reduced prevalence of hypertension in the Hisayama population. The association of serum total cholesterol with intracerebral hemorrhage is discussed based on the results during a 22-year follow-up period.

Decreasing trend in incidence and mortality from stroke in Hisayama residents, Japan.

The incidence and mortality from stroke during the period 1961 to 1976, among 1,621 subjects aged 40 and over at entry, in Hisayama community, Kyushu Island, Japan, were analyzed. A major agerelated decline in the incidence of cerebral hemorrhage and infarction occurred in both sexes. The average annual incidence of cerebral infarction also fell continuously in both sexes throughout the whole observation period. The 5-year annual mortality rate from cerebral hemorrhage also showed a decrease in men, but fluctuated in women. The 5-year mortality from cerebral infarction slightly increased in both sexes. Stroke, Vol 12, No 2, 1981

Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: a pathological study.

A pathological examination was performed on normotensive rats (NTR) and spontaneously hypertensive rats (SHR) following bilateral common carotid artery ligation. After ligation, diffuse and extensive cerebral infarcts in the carotid artery territory occurred frequently in SHR, while NTR occasionally had wellcircumscribed small infarcts. The posterior communicating arteries, which are the major anastomotic channels connecting the carotid and vertebrobasilar systems, did not show any anomalies and were well developed in SHR and NTR. Vascular changes secondary to hypertension, such as fibrinoid necrosis or thickening of the wall, were not observed in SHR. Because of the paucity of structural difference of the blood vessels, the more diffuse and extensive cerebral infarcts in SHR after carotid occlusion were attributed to the hemodynamic difference rather than the morphological difference between the two groups. The results of the present experiment suggest that hypertension per se, i.e., hemodynamic factors, may be operative for the development of cerebral infarction.

Separating changes in the intra- and extracellular water apparent diffusion coefficient following focal cerebral ischemia in the rat brain.

Selective intracellular (IC) and extracellular (EC) brain water apparent diffusion coefficient (ADC) values were measured in normal and ischemic rat brain. Selective T1‐relaxation enhancement of the EC water, using intracerebroventricular (ICV) infusion of an NMR contrast reagent (CR), was used to separate the IC and EC signal contributions. In the CR‐infused, normal brain (n = 4), T1 = 235 ± 10 ms and T2 = 46 ± 2 ms for IC water (85%) and T1 = 48 ± 8 ms and T2 = 6 ± 2 ms for EC water (15%). Volume‐localized ADCz (z‐gradient axis) values were 0.90 ± 0.02 (EC+IC), 0.81 ± 0.05 (IC), 0.51 ± 0.02 (EC+IC), and 0.53 ± 0.07 (IC), for normal, CR‐infused, ischemic, and ischemic/CR‐infused groups, respectively (ADC values are ×10‐3 mm2/s; n = 5 for each group). Imaging ADCz values were 0.81 ± 0.03 (EC+IC), 0.75 ± 0.05 (IC), 0.51 ± 0.04 (EC+IC), and 0.52 ± 0.05 (IC), respectively, for the same groups. Imaging ADCav (average diffusivity) values for the same groups were 0.70 ± 0.05 (EC+IC), 0.69 ± 0.06 (IC), 0.45 ± 0.06 (EC+IC), and 0.44 ± 0.06 (IC), respectively. These results suggest that the IC water ADC determines the overall water ADC value in normal and ischemic rat brain. Magn Reson Med 48:826–837, 2002.

Secondary decline in apparent diffusion coefficient and neurological outcomes after a short period of focal brain ischemia in rats

This study was designed to characterize the initial and secondary changes of the apparent diffusion coefficient (ADC) of water with high temporal resolution measurements of ADC values and to correlate ADC changes with functional outcomes. Fourteen rats underwent 30 minutes of temporary middle cerebral artery occlusion (MCAO). Diffusion‐, perfusion‐, and T2‐weighted imaging was performed during MCAO and every 30 minutes for a total of 12 hours after reperfusion (n = 6). Neurological outcomes were evaluated during MCAO, every 30 minutes for a total of 6 hours and at 24 hours after reperfusion (n = 8). The decreased cerebral blood flow during MCAO returned to normal after reperfusion and remained unchanged thereafter. The decreased ADC values during occlusion completely recovered at 1 hour after reperfusion. The renormalized ADC values started to decrease secondarily at 2.5 hours, accompanied by a delayed increase in T2 values. The ADC‐defined secondary lesion grew over time and was 52% of the ADC‐defined initial lesion at 12 hours. Histological evaluation demonstrated neuronal damage in the regions of secondary ADC decline. Complete resolution of neurological deficits was seen in 1 rat at 1 hour and in 6 rats between 2.5 and 6 hours after reperfusion; no secondary neurological deficits were observed at 24 hours. These data suggest that (1) a secondary ADC reduction occurs as early as 2.5 hours after reperfusion, evolves in a slow fashion, and is associated with neuronal injury; and (2) renormalization and secondary decline in ADC are not associated with neurological recovery and worsening, respectively. Ann Neurol 2000;48:236–244