Hyperacute thrombolytic therapy can be effective for patients with acute ischemic stroke, but may promote hemorrhagic complications. It is critically important therefore to determine the true incidence of hemorrhagic transformation after ischemic stroke, and to identify the factors underlying the phenomenon. In order to clarify these problems, 1, 487 consecutive patients with acute ischemic stroke admitted within 3 days after onset were analyzed using the database from the Japanese Standard Stroke Registry (JSSR). Hemorrhagic infarction (HI) was observed in 11% of the patients, of whom 51% were diagnosed as having cardiogenic embolism. In the patients with supratentorial infarction of cardiac origin, 28 % had HI (mild, 67%; moderate, 23%; hematoma, 10%). On multiple logistic regression analysis, the independent factors related with HI were found to be age (every decade, odds ratio [OR] 1.71, 95% confidence interval [CI] 1.19-2.45), prosthetic cardiac valve (OR 19.3, 95% CI 1.33-280.5), and NIHSS score on admission (OR 1.04, 95% CI 1.003-1.07). The patients with more severe HI were associated with a poorer outcome at discharge (OR 1.92, 95%CI 1.11-3.33) . Clinical outcome tended to be better in patients receiving thrombolytic agents than in those without the agents, while the incidence of HI was slightly more frequent in the former (not significant). It was confirmed that the JSSR database is useful for understanding and analyzing the status of stroke diagnosis and management throughout the nation, although revisions were needed in some formats.

View full abstract

We sequentially measured the plasma soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin) levels in patients with cerebral ischemia at three phases : within 48 hours, after one month and after 6 month from ictus. The plasma concentrations of sP-selectin were constantly increased from the acute phase to 6 months after ischemia, while the plasma concentrations of sE-selectin were elevated only at the acute phase, as compared with control subjects. The levels of sP- and sE-selectin appear to reach their peaks at 1 month after ictus in atherothrombotic infarction and at the acute phase in lacunar infarction. These findings could result from differences in the degree of platelet activation and/or extent of endothelial cell damage. The levels of sP-selectin were decreased in patients with atherothrombotic infarction treated with anti-platelet agents from 1 month to 6 months, as compared with patients treated without anti-platelet agents, reflecting the effect of anti-platelet agents. It should be emphasized that the levels of sP- and sE-selectin after cerebral ischemia fluctuate with pathophysiological changes such as platelet activation or endothelial cell damage, so that the sP-and sE-selectin levels could be useful for evaluating the effect of anti-platelet agents.

View full abstract

To investigate the effects of argatroban on plasminogen activator inhibitor-1 (PAI-1) and other components during fibrinolysis both in vitro and in vivo, human umbilical vein endothelial cells were cultured with and without addition of argatroban to the medium. On days 1 and 8 of culture, the PAI-1 and tissue plasminogen activator (t-PA) levels were measured in the culture solution and cytolytic solution. On day 8 of culture with argatroban, the PAI-1 level was significantly lower than that in the control medium, but the t-PA levels were similar in both media. The PAI-1 level in the cytolytic solution on day 8 of culture with argatroban was significantly lower than that in the control without argatroban. Argatroban was given through intravenous drip infusion to 9 patients with atherothrombotic cerebral infarction (ATI) and 9 patients with branch atheromatous disease (BAD). The plasma levels of PAI-1, t-PA, and TAT were then measured sequentially. The serum PAI-1 level was significantly higher in the ATI group (88.9±60.4ng/ml) than in the BAD group (27.9±8.4ng/ml) on day 1 of the disease and was significantly lower on day 3 of the treatment. In the BAD group, the PAI-1 level was within the normal range, both before and after the treatment with argatroban. The t-PA level in the ATI group was slightly higher than that in the BAD group before the treatment. These findings suggest that argatroban progressively decreases the release of PAI-1 from vascular endothelial cells, without any effect on t-PA release. The decrease in PAI-1 level following treatment with argatroban may be caused by inhibition of PAI-1 synthesis in the vascular endothelial cells.

View full abstract

The purpose of the present study was to clarify the clinical features of acute multiple brain infarction using diffusion-weighed MR imaging (DWI). We investigated 39 consecutive patients with supratentorial ischemic stroke showing recent multiple brain lesions on DWI performed within 7 days of stroke onset. The patients were classified into two groups according to the distribution of lesions on DWI : patients with small scattered lesions (group A), and those having a large cortical lesion with other scattered ones (group B). We compared the clinical characteristics, clinical course and outcome between the two groups. The patients in group A presented with a history of TIA within 7 days prior to the index episode, mild neurologic deficits on admission, fluctuations in neurologic deficits, and a good outcome was more frequently observed than in the group B patients. Severe stenosis of the major cerebral arteries was also encountered more frequently in the group A patients, and was inferred to be a potential contributing factor to small, multiple, scattered brain infarcts.

View full abstract

We report a cace of hypertensive encephalopathy (HTE) with unusual MRI findings. A 28-year-old woman was admitted to our hospital because of right putaminal hemorrhage with intraventricular rupture. Her arterial blood pressure was 206/140 mmHg. She was drowsy with severe headache and had left visual disturbance, horizontal gaze nystagmus, and mild left hemiparesis. T₂-weighted MRI revealed diffuse hyperintense lesions in the brainstem, cerebellum, and periventricular white matter. MRI also demonstrated swelling of the brainstem. Following the initiation of anti-hypertensive therapy, her clinical symptoms resolved rapidly. Follow-up MRI showed marked improvement of the above findings, with resolution of edema. Although occipital hyperintensity is thought to be a typical T₂-weighted MRI finding in HTE patients, our case displayed additional multiple lesions in other areas than the occipital lobe. It appears therefore that we should recognize possible variations in the pattern of MRI findings in patients with HTE.

View full abstract

In order to obtain reliable large-scale data on stroke management in Japan, we (J-MUSIC) conducted a multicenter study (consecutive registration) on stroke management from May 1999 to April 2000. During the study period, 16, 922 patients (10, 370 men and 6, 552 women) with acute ischemic stroke (≤7 days) were registered from 156 participating institutes.
Results are summarized as follows. (1) Women were older than men (73.6 vs. 68.7 year-old). (2) Patients were admitted to the department of neurosurgery in 49.4%, followed by neurology in 43.5% and stroke medi-cine in 7.1%. (3) Time from onset to admission was shorter than 3 hours in 36.8%, and 6 hours in 49.5%. (4) Patients were treated in stroke/intensive care units in 18.8%, and the rest of them were mostly treated in general wards. Outcome of patients with NIHSS score? 15 were better in those treated in SCU/ICU than those in general ward. (5) The median and mean of NIH Stroke Scale score were 5 and 8.0 ± 7.9 (SD), respectively. (6) Thrombolytic therapy for acute occlusion of the cerebral artery was done only in 2.5% of the patients. (7) Clinical category of stroke was lacunar in 36.3%, atherothrombotic in 31.1%, cardioembolic in 20.4%, unclassified in 5.7%, and TIA in 6.4%. (8) Proportion of atherothrombotic infarction was larger than that of lacunar stroke in Kanto and Kinki districts (urban areas), where diabetes mellitus and hypercholesterolemia as risk factors were more common than other areas. (9) Modified Rankin Scale at discharge was "0" in 18.5%, "1" in 28.8%, "2" in 13.3%, "3" in 8.3%, "4" in 14.4%, "5" in 9.5%, and "6" (dead) in 7.0%.
For better stroke managements, we need to make public education about an importance of prevention and early treatment of stroke, and to urge the government to approve tissue plasminogen activator as a therapeutic measure. In addition, we have to make effort for constructing better medical systems outside and inside the hospital for seamless care of stroke patients.

View full abstract

Gene transfer to blood vessels is an effective approach to alter vasomotor function, and a useful tool for studying vascular biology. Gene therapy for cerebrovascular diseases is an attractive approach, especially when pharmacological approaches are not effective. Preliminary data suggest that gene therapy may be useful for prevention of cerebral vasospasm after subarachnoid hemorrhage. As better ventors are developed, other clinical problems also may become targets for gene therapy.

View full abstract