To evaluate the incidence, clininal features, and strategy for management of bleeding complications, especially intracranial hemorrhage, accompanying antithrombotic therapy, we performed retrospective and prospective multicenter observational studies. In a retrospective multi-center trial, we reviewed the records of 947 patients with nontraumatic intracerebral hemorrhage (ICH). During antithrombotic therapy, 31.6% of the patients developed ICH. The proportion of cerebellar hemorrhage to total ICH increased from 5% of the patients without antithrombotics to 9% of those receiving antithrombotic therapy (p=0.046). Advanced age (p<0.0001), male gender (p=0.0001), diabetes mellitus (p=0.045), previous symptomatic ischemic stroke (p<0.0001), heart diseases (p<0.0001), and hematoma growth on computed tomography during the initial 24 hours (p=0.0043) were more frequent in the ICH patients taking antithrombotic agents than in those not taking the agents. In an interim analysis of a prospective multi-center trial, on which ≈4, 000 patients who received antithrombotic therapy were registered, 7 fatal and 50 non-fatal life-threatening bleeding events occurred, including 31 instances of symptomatic intracranial hemorrhage, during 19 months of follow-up as median. The annual incidence of life-threatening bleeding was 6.4 per 1, 000 person in the patients receiving single antiplatelets, 9.8 in those receiving multiple antiplatelets, 10.7 in those receiving warfarin, and 18.9 in those receiving warfarin plus antiplatelets.

View full abstract

Xenon CT CBF examination has much radiation exposure because of frequent scanning of the same slice. First, we did questionnaire investigation in Japanese 202 institutions in three months since December, 2004. The questionnaire result showed that the number of scan slices was 2.6±1.3 (mean±SD). The number of scans per one slice was 9.3±1.7. The x-ray tube voltage was 120 kV in most institutions. The x-ray tube current was 347±128 mAs. We got an answer from a 54 institution about CTDIw value. The radiation exposure in these institutions was 1, 108.3+/-874.4 mGy·cm.
Second, we studied the influence that decrease of scan frequency gave to radiation exposure and cerebral blood flow value. In a 4 slices scan with a CT device of CTDIw 39.6 mGy, radiation exposure decreased by 634 mGy when we changed scan frequency from seven times to three times. The decrease of scan frequency resulted in cerebral blood flow increase of 3-5ml/100mg/min. In conclusion, among Japanese institutions, number of scan slices and scan frequency per one slice were various. Making of a guideline and reconsideration of the scan conditions are necessary for reduction of radiation exposure.

View full abstract

Background and Purpose: Although parenchymal hypoattenuation (PH) indicates severe ischemic injury, brain swelling without concomitant hypoattenuation (BS) is thought to be more benign. We have clarified the clinical significance of BS.
Methods : A total of 53 patients (34 men, 19 women, mean 69.7 years old) with acute embolic stroke was enrolled. PH and BS were evaluated on baseline CT. Residual cerebral blood flow (rCBF) was determined by 99mTc-HMPAO SPECT performed within 6 hours of onset. Difference in patients' age, gender, neurological severity (NIHSS), CT time and rCBF, were evaluated among patients with PH, BS and negative early CT signs (NEG) using one-way ANOVA with Scheffe's post hoc analysis. Results : The CT time (F = 4.369, P = 0.018) and the rCBF (F=7.881, P = 0.001) were significantly different among NEG (16 patients), BS (5 patients), and PH (32 patients) groups. BS was observed within 3 hours of onset. CT time was significantly longer in PH group compared to NEG group. PH and BS groups exhibit significant lower rCBF compared to NEG group, although no statistical difference was observed between BS and PH groups.
Conclusions: We speculated that BS was observed within early hours of onset, and then accompanied by concomitant parenchymal hypoattenuation.

View full abstract

Non-contrast CT and diffusion-weighted MRI (DWI) are widely used for assessing patients with acute ischemic stroke including candidates for thrombolytic therapy. Early CT signs, still a gold standard as the diagnostic measure for thrombolysis, are quite subtle and strongly depend on image quality. We evaluated 76 patients (47 male, mean age 71.0 yrs) with ischemic stroke of the anterior cerebral circulation who underwent CT and DWI within 6 hours of onset. The scans were examined separately by two neurologists in a blinded fashion with knowledge of the affected hemisphere. Detection of acute ischemic changes were significantly higher on DWI (72/76, 95%) compared with that on CT (50/76, 66%)(P<0.0001), especially in cases with subcortical lesions (P<0.001). Detection of the lesion with more than 33% of MCA involvement, which should exclude from the thrombolitic therapy, was somewhat higher for DWI (26/26, 100%) compared with CT (22/ 26.85%).
DWI is more sensitive than CT in the identification of acute ischemic stroke and can visualize major ischemia more easily than CT. Additional studies are required to determine whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.

View full abstract

CT is a widely used imaging modality for diagnosis of cerebral vascular disease. However, the sensitivity of detection at early stage of cerebral infarction is not adequate depending on the ability of observers and instruments. The high sensitivity of diffusion-weighted imaging on MRI for the diagnosis of acute cerebral infarction has bee reported. Furthermore, MRI can demonstrate perfusion and vascular information without usage of contrast medium. In addition, the recent work showed that susceptibility imaging on MRI has the same quality to detect acute cerebral hemorrahge as CT. We consider that MRI has a possibility to become the first selected modality for the acute cerebral infarction.

View full abstract

Branch atheromatous disease has been recognized as one of the types of stroke which is often associated with clinical deterioration. We investigated the correlation between diffusion weighted imaging (DWI) findings and clinical courses of 33 patients with BADs in the territory of the lenticulostriate arteries. The DWI findings associated with the poor outcomes (modified Rankin Scale ; mRS>or = 3) are (1) the larger lesion size in a direction perpendicular to axial section and (2) the lesions located in the inferior portion of basal ganglia. The findings correlated with progressive motor deficits are (1) the lesions closer to the posterior limb of internal capsule (medial type) and (2) the lesions located in the inferior portion of basal ganglia. These characteristics of DWI may play an important role to distinguish the progressing ischemic strokes as BAD from non-progressing ones.

View full abstract

Diffusion-weighted imaging (DWI) is widely applied for evaluating patients with acute ischemic stroke. However, its display conditions are different among institutions, and reliability of the apparent diffusion coefficient (ADC) has not been validated enough. Recently, we proposed an easy-to-use technique to standardize display conditions, in which window width and level are normalized by the signal intensity of brain tissue on b0 images. We carried out a multi-institutional multivendor study, and revealed that the technique successfully minimized difference in the display condition among institutions and vendors. On the other hand, we found that the ADC value is significantly different among vendors and static magnetic fields, suggesting that the ADC should be evaluated semiquantitatively. Standardization and technical advancement are considered to be necessary to improve reliability of DWI in acute stroke managements.

View full abstract

We analyzed brain perfusion status using the new non-enhanced MR sequence, SWI MR venography, in patients with acute ischemic stroke.
Twenty-one patients who had acute cortical infarction within 24 hours after symptom onset were enrolled. Seventeen of these patients showed spontaneous blood oxygen level-dependent (BOLD) signaling by SWI, which indicated abnormal venous flow. In this group, increased BOLD signals disappeared before the phase of vasogenic edema, therefore increased BOLD signals may be related to "misery perfusion" on perfusion imaging in acute stroke. Evidence of embolous signals was seen with SWI in 13 patients, compared with 7 patients by T2* sequence.
The SWI technique is a proven noninvasive and powerful MR sequence for evaluating brain perfusion abnormality and embolic signals after acute stroke.

View full abstract

Patients with metabolic syndrome (MetS) are at high-risk for future cardiovascular events. The relationship between MetS and stroke in Japan, however, has not yet been elucidated. We assessed an association of MetS with ischemic stroke. We performed a cross-sectional study consisting of consecutive 311 patients with ischemic stroke (M/F 209/102, mean age of 70 years) who were admitted to our hospital within the first 7 days from February 1 in 2004, and of 611 people (418/204, mean age of 70 years) in a general population in Hisayama town. The diagnosis of MetS was made according to the Adult Treatment Panel III of the National Cholesterol Education Program (NCEP), the World Health Organization (WHO), International Diabetes Federation (IDF), and the Japanese Society of Internal Medicine (JSIM). MetS was present in 24% of the stroke patients by NCEP, 15% by WHO, 25% by IDF, and 21 % by JSIM definition. The number of traditional vascular risk factors was significantly correlated with the presence of ischemic stroke. Stroke patients had more frequently hypertension (relative risk 2.5), diabetes mellitus (3.8), low HDL-cholesterol (13.1), increased level of CRP (3.2), and less frequently hypertriglyceridemia (0.3), hypercholesterolemia (0.5) as compared to people in Hisayama town. MetS of any definitions was not significant risk factor for ischemic stroke in this study.

View full abstract

Background-Metabolic syndrome is characterized by a cluster of four cardiovascular risk factors: visceral obesity, insulin resistance, dyslipidemia, and hypertension. This study investigated the relationship between metabolic syndrome and first-time ischemic strokes in a cohort of Japanese subjects.
Methods-The subjects were 2, 726 Japanese adults with no history of stroke and no neurological abnormalities, who participated in voluntary neurological health screening at the Institute of Shimane Health Science, Japan, between 1988 and 2002 (1, 507 men and 1, 219 women, 57.4 ± 7.9 years old at entry). Each subject was evaluated for an average of 6.3 ± 3.8 years. However metabolic syndrome was defined using the criteria for Japanese published in April 2005, we used BMI≥25 as the definition of central obesity instead a waist circumference throughout the study.
Results-Metabolic syndrome was diagnosed in 13.9% of the men and 4.3% of the women. Adjusting for age and smoking, female subjects with metabolic syndrome had a 7.7-fold increased risk of suffering an ischemic stroke, whereas metabolic syndrome did not increase the risk of ischemic stroke in men. Furthermore, for females, obesity alone did not increase the risk of ischemic stroke, but obesity plus at least one other component of metabolic syndrome increased the risk of ischemic stroke compared with females who had no components (6.5, 28.8, and 23.9 fold for one to three additional components, respectively). By contrast, males with obesity alone or with one or two additional components did not have an increased risk of ischemic stroke, while males with obesity and all three other components did have an increased risk of ischemic stroke compared with males with no components (four fold).
Conclusions-Metabolic syndrome leads to a greater risk of ischemic stroke in women than in men.

View full abstract

J-TRACE is a nationwide multi-center cooperative study to prospectively observe vascular events during 2 to 4 years of period in patients with stroke, MI and atrial fibrillation (afib), which are three major thromboembolic diseases. Until July 24, 2006, 6, 163 patients have been registered at 273 sites. We analyzed interim results of the baseline data.
History of stroke (14.1 %) was far more common than history of MI (2.9%) in stroke patients, while history of stroke (6.3%) was less frequent than history of MI (8.2%) in MI patients. History of stroke (15.1%) was far more frequent than history of MI (3.7%) in afib patients. Hypertension was the most frequent risk factor (71.8%) in stroke patients, while hypercholesterolemia was the most frequent risk factor (64.2%) in MI patients. Average number of risk factors was higher in MI patients (2.32) than in stroke patients (1.87). Hypertension, hypercholesterolemia, history of MI, and age >75 years were more frequent in afib patients with than without history of stroke. Patients with more than two of hypertension, diabetes, and hypercholesterolemia in addition to obesity were more frequent among patients with MI (23.6%) than stroke (14.1%) or afib (13.1%) patients.

View full abstract

To determine clininal features of Japanese patients who developed intracerebral hemorrhage (ICH) while receiving antithrombotic agents, we performed a retrospective study based on the medical records of 947 patients with nontraumatic ICH from 11 institutes between 1999 and 2003. On the treatment with antithrombotic therapy were 31.6% of the patients (20.7% of patients taking antiplatelets, 8.1% taking warfarin, and 2.5% taking both). The proportion of cerebellar hemorrhage to total ICH increased from 5% of the patients without antithrombotics to 9% of those on antithrombotic therapy (p=0.046). Advanced age (p<0.0001), male gender (p=0.0001), diabetes mellitus (p=0.045), history of ischemic stroke (p<0.0001), heart diseases (p<0.0001), and hematoma growth on computed tomography during the initial 24 hours (p=0.0043) were more frequent in ICH patients taking antithrombotic agents than in the others.

View full abstract

"Guideline for Stroke Treatment 2004" published in Japan strongly recommended that acute stroke patients should be managed in dedicated stroke care unit or stroke unit. We conducted a nation-wide survey of all hospitals providing acute stroke care. We sent a questionnaire to 7, 835 hospitals and obtained 2, 603 answers (33.2%). According to the meta-analysis by Stroke Unit Trialists' Collaboration, service organizations were classified into five categories as a hierarchy in descending order as follows ; acute stroke units, comprehensive stroke units, mixed rehabilitation ward, mobile stroke team, and general medical ward. Only 8.3% of hospitals had organized stroke units (acute stroke units ; 0.9%, comprehensive stroke units ; 7.4%), and 63.8% of hospitals managed acute stroke patients in general medical words. The categorization of stroke service organizations was highly correlated with the number of patients admitted in a year. We compared performance levels of the key elements recommended for establishing primary stroke centers by the Brain Attack Coalition among the five categories, such as acute stroke teams, stroke units, written care protocols, and an integrated emergency response system, availability and interpretation of computed tomography scans 24 hours everyday, access to neurosurgeon within 2 hours and rapid laboratory testing. Currently there are very few hospitals with performance levels required for the primary stroke center. More importantly, measures were taken for the quality improvement of stroke care only by 6.5% of hospitals. Intravenous thrombolytic therapy is now widely available in Japan. Establishment of clearly defined stroke units or stroke care units is urgently needed.

View full abstract

Progression of investigator-initiated clinical trials has been hampered by the lack of efficient and costless infrastructure for driving the trials, with a paucity of definitive clinical evidence derived from our country. In order to construct such infrastructure without spoiling pertinent quality, this study prepared electronic data capture and its facilitating systems for a large-scale clinical trial model : multi-center randomized controlled trial for the secondary prevention of stroke, which is called J-STARS. Particularly, we have developed 1) web-based patient registration and data collection system, 2) automatic mail delivery system notifying follow-up data submission, and 3) PDF-based severe adverse events reporting system. Also, we have determined laborsaving data management procedure for the trial, in which bad data are extracted from the database and inquiry mails are semi-automatically sent out. By the preparation of these systems and procedure, infrastructure for conducting investigator-initiated large-scale clinical trials appears to be constructed. The infrastructure can be applied to the trials in other medical fields, potentially allowing for a promotion of such trials in our country.

View full abstract

The Northern Hokkaido of Japan is an aged and an underpopulated area. We started the stroke registration system in this area from July 2002, and evaluate as follows. 1) The type of stroke (NINDS, CVD-III), 2) severity on admission (NIHSS score), 3) outcome (modified Rankin Scale), 4) risk factors of stroke, and 5) secondary prevention with antithrombotic therapy and recurrence ratio. From July 2002 to June 2005, 792 patients (57.4% male and 42.6% female) with acute stroke were registrated. The mean age (±SD) of patients were 71.0 ± 12.1. The type of stroke distributes cerebral infarction in 64.1%, intracerebral hemorrhage in 26.3%, subarachnoid hemorrhage in 9.3%. The clinical category of cerebral infarction was lacunar in 38.0%, atherothrombosis in 33.7%, cardioembolism in 13.6%. In total 792 cases, 38 cases were recurrent the stroke. The annual recurrence ratio was 2.6% in lacunar group, 6.9% in atherothrombotic group, and 13.6% in cardioembolic group.
In the Northern Hokkaido, proportion of intracerebral hemorrhage was still larger compared with the major collaborated stroke study in Japan. And in ischemic stroke group, lacunar infarction was the largest category even now.

View full abstract

Dysphagia is a common and disabling symptom in stroke patients, and prediction of prolongation of dysphagia in its acute stage is very important from several standpoints, including selection of the treatment strategy, planning of care, and the QOL of the patients.
We retrospectively analyzed the data of 33 stroke patients in whom videofluoroscopy (VF) had been performed to check for the swallowing function, and investigated the predictive factors for dysphagia after stroke. Of the 33 patients, 25 patients had had ischemic stroke and 8 had had hemorrhagic stroke. Twenty patients (39%) could take their regular meals orally by the 30th hospital day, while 12 patients (36%) developed pneumonia during the first 30 days of hospitalization. Predictive factors of taking regular diet by oral feeding were 1) consciousness level, 2) location of lesions, and 3) severity of dysphagia as assessed by VF. While a predictive factor for pneumonia was advanced age of the patient. Dysarthria was not a predictor of dysphagia.
Comprehensive evaluation of the swallowing function by detailed clinical evaluation and VF should be conducted in acute stroke patients, to enable timely identification and management of dysphagia in these patients.

View full abstract

Background : The purpose of this study was to assess the prevalence of impaired glucose tolerance (IGT) and insulin resistance in stroke patients without previously known diabetes by performing a 75g oral glucose tolerance test (75g OGTT).
Methods : We recruited 203 stroke patients (atherothrombotic infarction (ATI) ; 42.2%, lacunar infarction (LI) ; 29.6%, cardioembolic infarction (CE) ; 11.3%, cerebral hemorrhage (Hem) ; 11.8%, transient ischemic attack ; 3.9%, others; 1.2%). 75g OGTT was used to evaluate the disorders of glucose metabolism. We investi-gated the relationships between the incidence of IGT and insulin resistance using HOMA-R and stroke sub-types.
Results : The disorders of glucose metabolism were present in 62.7% of patients without previously known diabetes. Diabetes and IGT were diagnosed in 38% and 28%, respectively, of patient with ATI. IGT was observed 35% with a single risk factor (hypertension or hyperlipidemia) and 65% with two risk factors (both of hypertension and hyperlipidemia). HOMA-R was markedly higher level in patients with ATI than with another stoke subtypes.
Conclusions : A screening by 75g OGTT was useful for diagnosis of the disorders of glucose metabolism in patients with no prior history of diabetes. Insulin resistance might be an important role for the progression of atherosclerosis in patients with ATI.

View full abstract

Confusion often occurs in acute brain infarction, but its character and effective therapy have not been examined well. We divided 49 patients with acute brain infarction into the confusion group (20 patients) and the non-confusion group (29), and compared the character of each group. The confusion group showed older age (79±2 years old vs. 72±2, p=0.0075) and lower scores of Hasegawa Dementia Scale (15.3±1.8 vs. 21.2±2.1, p=0.0183) than the non-confusion group. Right hemisphere lesions, especially the front-parietal lesions, were more often observed in the confusion group. Four of 5 patients who did not receive pharmacotherapy and only 7 of 15 patients who received pharmacotherapy, recovered from confusion. On the other hand, recovery from confusion was quicker in patients with pharmacotherapy than without pharmacotherapy. Patients with confusion stayed significantly longer in the hospital (72.9±11.3 days vs. 48.9±6.2, p < 0.05) and modified Rankin Scale was significantly higher in patients without confusion (2.6±0.3 vs. 1.9±0.3, p<0.05). According to these results, patients with confusion showed poorer outcome. We need to establish effective therapies against confusion in acute brain infarction.

View full abstract

Systemic complications such as pneumonia, urinary tract infection, heart failure and others had affects to the outcome of the patients of intracranial hemorrhage. Systemic complications were occurred in 40% of all intracranial hemorrhage patients and in even 20% of the patients who had only a slight illness over Glasgow Coma Scale 13. Infectious diseases accounted 60% of all complications in the intracranial hemorrhage patients. We founded new stroke care unit (SCU) and changed some strategies for these complications. Aggressive endotracheal intubation and prophylactic antibiotics administration were very effective to decrease the rate of aspiration pneumonia which was the most common complication in the patients of intracranial hemorrhage. However these new strategies reduced the rate of systemic infectious complications, the outcome of these patients was improved only to "moderate" from "poor". Reduction of systemic complications led to decrease the rates of death and vegetative state due to intracranial hemorrhage. We emphasized the importance of intensive care for acute stage of intracranial hemorrhage in SCU, because it made the patients possible to leave from bedridden.

View full abstract

CADASIL is an inherited cerebrovascular disease that cause migraine-like headache and recurrent stroke. Mutations of Notch3 gene on chromosome 19 are responsible for CADASIL. Usually these mutations might change the number of cysteine residue. We examined the mutation of Notch3 gene in independent 21 Japanese patients with leukoaraiosis without hypertension. Four patients were in our hospital, and 17 patients were from other hospitals in mainly Western Japan. We examined the DNA extracted from the peripheral blood in all patients with informed consent. We analyzed exon 3-4, 11 and 19 of Notch3 with PCR-sequencing method. In seven patients, we examined samples obtained by skin biopsy to detect GOM (granular osmiophilic materials) with electron microscope. Five patients revealed to have mutations related with cysteine (R90C, C123Y, R133C, R153C and R169C) and one patient with V237M had GOM in arterioles of skin. Then six patients were diagnosed to have CADASIL. We could not find GOM in other 6 biopsy samples including three geneticaly diagnosed CADASIL patients. All patients diagnosed as CADASIL had family history of stroke.
We think CADASIL is popular also in Japan, and genetic examination should be done in patients with leukoaraiosis without hypertension especially who had family history of stroke.

View full abstract

Background—deCODE genetics, Inc. identified a candidate locus (STRK1) for cerebral infarction with a significant LOD score at 5q12 in Caucasians in 2002, and subsequently identified the PDE4D gene as a susceptibility gene at this locus in 2003. The aims of this haplotype-based case-control study were to confirm, using microsatellite markers and single nucleotide polymorphisms (SNPs), whether PDE4D is also a susceptibility gene for cerebral infarction.
Methods—Cerebral infarction was defined as non-cardiogenic ischemic stroke with signs and symptoms lasting longer than one month in duration. We genotyped 208 Japanese cerebral infarction patients and 270 non-cerebral infarction controls for 31 SNPs, three dinucleotide microsatellites, and one tetranucleotide vari-able number tandem repeat. Haplotypes were constructed and their frequencies compared between the cere-bral infarction patients and the controls.
Results—Seven haplotype blocks were found in the STRKI locus by the linkage disequilibrium analysis. The haplotype-based case-control study revealed that, in addition to the region of the PDE4D gene (p = 0.002), another region (p<0.001) also existed within the STRK1 locus.
Conclusions—Our results suggest that there may be a susceptibility region other than that of the PDE4D gene within the locus in Japanese subjects.

View full abstract

Brain edema is a major and often mortal complication of brain ischemia. Vascular endothelial growth factor (VEGF) is also known as a potent vascular permeability factor and may play detrimental roles at the acute stage of brain infarction. We explored protective effects of gene transfer of soluble flt-1 (sFlt-1), a natural inhibitor of VEGF, on focal brain ischemia. Adenoviral vectors encoding sFlt-1 or β-galactosidase were injected into the lateral ventricle 90 minutes after photochemical distal middle cerebral artery occlusion in male spontaneously hypertensive rats. The transduced sFlt-1 was released into the cerebrospinal fluid from the ventricular wall and significantly increased 1 and 7 days after sFlt-1 transfection. Seven days after ischemia, sFlt-1 gene transfer significantly attenuated infarct volume (by 29%) and monocyte/macrophage infiltration (by 27%) although there were no reductions in angiogenesis by sFlt-1 overexpression. These results suggest that sFlt-1 gene therapy targeting brain edema in acute stage of brain ischemia may be usefulness for brain infarction.

View full abstract

ES cells are self-renewing, pluripotent cells derived from the inner cell mass of the preimplantation blastocyst. We transplanted ES cell-derived neural progenitor cells into ischemic brain and assessed the survival and differentiation of these cells. We confirmed that these cells could survive and differentiate in the mouse ischemic brain by immunohistochemistry. These results indicates that ES cell-derived neural progenitor cell is a candidate of the method of cell therapy for stroke.

View full abstract

It was reported that the transplantation of the mesenchymal stem cell (MSC) protects against the cerebral infarction in the acute phase. Using transgenic rat that express the enhanced green fluorescent protein (EGFP), we investigated migration of MSCs in floresense microscopy and the infarction volume was measured with the use of 2, 3, 5-triphenyltetrazolium chloride (TTC) stain.The EGFP enhanced MSC were transplanted 3 h after the transient 90 min the middle cerebral artery occlusion. The animals were allowed to survive for 48 hours after stroke and the migration of transplanted MSCs were examined with fluorescence microscopy. The routes of the transplantation were intraventricle, intracerebral, intravenous and intracisterna magna. The MSC were distributed mostly in the penanbra area and the distribution pattern was as fillowes:
(1) Intraventricle route ; the MSCs were significantly distributed in the striatum of paraventricle area and few in the cortex. (2) Intracerebral route ; the MSC were prominently distributed in the striatum but few in the cortex. (3) Intravenous route ; the MSC were averagely in the striatum and the cortex. (4) Intracisterna magna route ; the MSC were sparsely in the striutum and aboundingly in the cortex.
The MSCs showed a tendency to distribute in the striatum more than in the cortex. However, the infarction volume was reduced in the striatum than the cortex. The distribution of MSCs were not correlated to protective effect. The precise mechanism of the neuroprotective effects of MSC in the rat after MCAO is not known. A reasonable hypothesis, more consistent with our findings, is that the interaction of MSC with the ischemic brain microenviroment leads to production of trophic factors, which reduce apoptosis in the cortex and striatum.

View full abstract

The aim of cell transplantation is to replace damaged area. But transplanted neural stem/progenitor cells (NSPCs) didn't treat lesion core. We transplanted adult NSPCs modified to secrete GDNF in order to make transplanted NSPCs replace ischemic area more effectively.
NSPCs were harvested from subventricular zone (SVZ) of adult rats and cultured with EGF by using neurosphere technique. Expanded NSPCs were transfected with fiber-mutant F/RGD adenovirus containing GDNF (NSPC-GDNF) or EGFP (NSPC-EGFP) gene. The best transfection efficiency was derived from GDNF ELISA. At first, NSPC-GDNF or NSPC-EGFP cells were transplanted into the ischemic boundary zone of MCAO model of Wistar rats in the acute stage (allogenic transplantation). NSPC-GDNF group had a significantly better result in behavioral test and infarction volume than NSPC-EGFP group. Subsequently, NSPC-GDNF or NSPC-EGFP cells were transplanted into the damaged CAI of global ischemia model of Fischer344 rats in the chronic stage (syngenic transplantation). NSPC-GDNF cells migrated and differentiated into neuron as replacing the damaged CAI of hippocampus partially. Moreover, NSPC-GDNF group had shown the activation of neurogenesis of endogenous NSPCs.
Consequently, we confirm NSPC-GDNF have neuroprotective effect and can replace damaged area. We think this result suggests that NSPC-GDNF cells can bring a good result in autologous-transplantation.

View full abstract

Thrombolytic treatment of intravenous rt-PA is known to be effective for treatment of acute ischemic stroke with the onset of less than 3 hours. On the other hand, because the time window of the treatment is limited to be within 3 hours for fear of serious intracranial hemorrhagic complication, few patients will be indicated for the thrombolytic treatment.
In this paper, simulation and indication of the treatment were retrospectively studied from our stroke center database.
A total of the 371 acute ischemic stroke patients admitted to our stroke center during 2004 were classified into lacunar stroke (39%), cerebral embolism (26%), cerebral thrombosis (21%) and transient ischemic attack (7%). Of all the patients, 61 (16%) arrived at our hospital within 2 hours of the onset, of whom only 14 (4%) were considered to be indicated for the thrombolytic treatment. To increase the rate for the treatment, a further enlightenment action to citizens and practicing physicians will be necessary.

View full abstract

Background and Purpose:Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) within 3 hours after onset of cerebral ischemia was approved in Japan in October 2005. Preceding using rt-PA for acute cerebral infarction, we built a simulation model of patient flow using inpatient data and clarified issues of in-hospital systems.
Methods:We retrospectively analyzed consecutive 485 patients with acute ischemic stroke admitted in our center from May 2002 to October 2005. We analyzed the patients who arrived at our center within 120 minutes after the onset, because at least 60 minutes by the admission will be required for evaluating of patient status and informed consent. We estimate the ratio of patients who fulfilled inclusion criteria for intravenous administration of rt-PA in the patients with acute ischemic stroke. We also assessed interval from the arrival to the admission in these patients and factors related to the interval.
Results:There were 148 patients (30.5%) who arrived at our center within 120 minutes after the onset of symptoms. There were 94 men and 54 women. Age was 73.9±10.0 years-old (Mean±SD). The time from the onset to the arrival was 78.8±39.8 minutes. Baseline National Institutes of Health Stroke Scale (NIHSS) was 12.4±9.6. In these patients, only 32 patients (21.6%) fulfilled criteria for the inclusion prior to the admission. The remaining patients were excluded due to the following reasons:unknown onset time, 55; regression of symptoms, 11; mild symptom (NIHSS54), 47; history of intracranial hemorrhage, 3;convulsion, 3; extensive early CT sign, 35 and other reasons, 8. In the included 32 patients, five patients needed more than 180 minutes from the onset to the admission. Finally, 27 patients (5.6% in the all patients) admitted within 180 minutes after the onset and fulfilled the inclusion criteria. In 148 patients, 81 patients were not admitted within 60 minutes after the arrival. Sixty-seven patients were admitted within 60 minutes after the arrival and had significant higher NIHSS than those admitted more than 60 minutes. Age, referral hospital, ambulance or arrival time was not significant factor for the interval from the arrival to the admission.
Conclusion: We estimated the candidate for acute thrombolysis using intravenous rt-PA to be 5.6% of total patients with acute ischemic stroke. Patient evaluation frequently required more than 60 minutes prior to the admission, even if the patients arrived at our center within 120 minutes after the onset. We should establish the in-hospital system to reduce the time for patient evaluation.

View full abstract

In one year before intravenous thrombolysis with tissue plasminogen activator (t-PA) to patients within 3 hours of acute ischemic stroke became an insurance adjustment in Japan, we tried to select the example presumed that it was a t-PA indication. In 264 ischemic stroke and transient ischemic attack (TIA) patients within seven days of stroke onset, patients who arrived within 3 hours were 99 (37.5%) and within 2 hours were 78 (29.5%). It was a tendency that "onset to door" time was short in cardioembolic brain infarction and TIA. In 99 patients who had arrived within 3 hours from stroke onset, aged ≥75 years were 42 (42.4%). Though examples of t-PA indications except the taboo item were 31 (11.7%), the example of indications has decreased to 11(4.2%) when excepting the careful administration item (NIHSS score≥23, JCS≥100 or aged≥75 years old). To improve the effectiveness of t-PA, a further approach on shortening "onset to door" time is important, and additionally the accumulation of cases is also necessary for the establishment of the safety and the effectiveness of t-PA to the elderly patients aged≥75 years old.

View full abstract

We investigated the treatment outcome of revascularization for acute ischemic stroke and reviewed therapeutic strategy of endovascular therapy and intravenous rt-PA therapy after the approval of rt-PA. We performed adaptive determination of revascularization using MRI (DWI/PWI) for all acute stage, and intravenous rt-PA therapy was performed only for confirmed cases in a principal bronchus artery in MRA.
We took intravenous rt-PA therapy for cardioembolic MCA occlusion of less than 3 hours and performed endovascular treatment which were the brain blood vessel expansion technique that we used UK intraarterial injection or a balloon and stent for besides it. As for the treatment strategy of revascularization, that we perform the treatment that conformed to eligibility criteria of intravenous rt-PA therapy is recommended for future acute stage without receiving it for a case of less than 3 hours than the onset. In addition, it should be reviewed adaptation of brain endovascular treatment for the patient beyond three hours by evaluating cerebral circulation dynamics by imaging such as DWI/PWI MR. As for the revascularization, maintenance of early transportation organization of the local acute stroke patient and architecture of inside the hospital organization are important for acute stage after intravenous rt-PA therapy certification.

View full abstract