Fluvoxamine is a serotonin selective reuptake inhibitor. We treated two patients suffering from poststroke depression (PSD) with fluvoxamine and evaluated its effect using several different depression scales, i.e, Beck's Depression Inventory (BDI), Zung's Self-rating Depression Scale (SDS), Hamilton's Depression Rating Scale (HDRS), the Post-stroke Psychiatric Symptoms Rating Scale (PPSRS), Japan Stroke Scale-Depression Scale (JSS-D), and Japan Stroke Scale-Emotional Disturbance Scale (JSS-E) . At 8 weeks after the start of fluvoxamine, the scores on the SDS, HDRS, PPSRS, JSS-D, and JSS-E were improved, Mild cognitive impairment was also improved by fluvoxamine in one patient. The present results indicated that the JSS-D and JSS-E were useful for the evaluation of PSD as well as the other depression scales. Furthermore, an effect of fluvoxamine on PSD was suggested.

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While intracranial hemorrhages represent the primary neurological complication of local intraarterial fibrinolysis (LIF) for acute embolic stroke patients, recurrent thromboembolisms following such therapy are extremely rare. We report a case of probable recurrent embolism of the internal carotid artery due to the dislod ment of a left atrial free-floating ball thrombus during LIF for ipsilateral cerebral embolism. A 75-year-old man who exhibited motor aphasia and right hemiplegia was transferred to our institute at one hour after the onset. Computed tomography (CT) of the head on admission revealed neither a high density area nor early CT signs, and dynamic CT scans demonstrated a delay of time to peak in the left hemisphere, as calculated from time-density curves. An electrocardiogram showed atrial fibrillation, and emergent cerebral angiography disclosed an occlusion of the left middle cerebral artery. On this basis, we diagnosed the patient as having cerebral embolism and considered him as a candidate for LIF. After obtaining informed consent from his family, we performed LIF with urokinase (240, 000 units) for the culprit arteries and achieved a partial recanalization of them. When we attempted to complete the procedure and reevaluated the cerebral vessel using contrast material via a guiding catheter inserted in the left internal carotid artery (ICA), we found pooling of the material in the ICA and considered it as constituting total occlusion of the ICA. Immediately afterwards, his respiratory condition and consciousness level deteriorated. The differential diagnosis of mechanisms of ICA occlusion that we considered included possible recurrent embolism from a left atrial thrombus and possible iatrogenic dissection of the ICA resulting from insertion of the guiding catheter. We were worried about the latter mechanism and performed emergency carotid stenting to restore the flow of the ICA. As a result, we achieved complete recanalization of the ICA without additional distal embolisms, and the patient's respiratory condition improved soon after the recanalization. Following this procedure, we treated him with intravenous heparin. An echocardiogram performed on the second day after adimssion revealed a left atrial free-floating ball thrombus without mitral valve disease. We assume that the ICA occlusion was due to recurrent embolism, and the embolus originated from a left atrial free-floating ball thrombus that was formed as a com-plication of chronic atrial fibrillation and whose dislodgement was facilitated by the urokinase, although we have no direct proof of this assumption, since an echocardiogram was not performed before the embolic event. CT scans on the third day demonstrated infarction of the frontal-parietal lobe on the left side and the patient' s neurological symptoms did not improve subsequently. Four months later, he died from pneumonia and con-gestive heart failure. Necropsy was not permitted. The present case shows that during LIF for acute embolic stroke, we must pay attention not only to hemorrhagic complications but also to recurrent systemic embolisms, particularly in patients with a left atrial free-floating ball thrombus, and echocardiograms undertaken before LIF may be of importance in order to assess correctly the risk of such embolization and to modify the therapeutic strategy appropriately.

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The outline of the evidence-based guideline for managements of the Japanese patients with cerebral in-farction were presented, which was prepared by the study group on "Evidence-based guideline for the management of cerebral infarction" of Japanese Ministry of Health, Labour and Welfare.
The present state of the evidence on the therapies of cerebral infarction and the various problems concerning this guideline development were discussed.

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Multiple modalities for imaging of the cervical carotid artery (CA) are reviewed, and their indications for obstructive carotid diseases are discussed.
Ultrasonography is a completely non-invasive modality. It is not only a primary tool for screening of the carotid artery but is capable of minute tissue characterization and flow velocity measurements, which will be discussed in detail somewhere else in this symposium.
The standard method for MR angiography (MRA) for the cervical CA is contrast-enhanced MRA (CE-MRA), which employs T1shortening by intravenous gadolinium chelate injection. With use of dedicated neurovascular coil, MRA of the major cervical arteries from the aortic arch up to the skull base is obtained in 15 seconds. Although the spatial resolution is limited and there is possible signal loss from phase dispersion caused by non-laminar flow, it is a minimally invasive method for screening of the cervical arteries. Recent introduction of parallel imaging technology has added multi-phase capability to CE-MRA.
CT angiography is another standard modality for carotid imaging. With advent of multi-detector CT (MDCT) scanner, it is possible to acquire isotropic three-dimensional data set of the whole range of cervical vessels in a few seconds, minimizing motion artifact from pulsation and respiration. With its capability of high spatial resolusion imaging, it will replace conventional angiography in most of the clinical settings.
Plaque imaging by MRI is a novel method to evaluate carotid plaque using special high-resolution imaging technique such as black blood sequence. Its clinical goal is to identify vulnerable plaque by characterization with multi-sequence imaging. A few of the imaging features indicative of vulnerable plaque include contrast enhancement on post contrast T1-weighted images and disruption of fibrous cap on T2 * -weighted images.

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Recently, the number of patients with severe carotid stenosis is increasing in Japan. During these 2 years (2001-2002), 205 patients with severe internal carotid stenosis were admitted to our hospital, of whom 94 patiens (45.9%) underwent carotid endarterectomy (CEA). According to our criteria of carotid ultrasound sonogram (US), we recommend the precise examination and CEA for the patients with>90% stenosis on the US axial view, over 200cm/sec in peak sysytolic velosity at the most stenotic lesion, and>1.3 in endodiastolic flow velosity ratio of common carotid artery (intact/lesion side). Transoral carotid ultrasonograpy are essential for the assessment of distal internal carotid artery, and trascranial color coded doppler ultrasonography are also useful for the management of the CEA patients to protect against hyperperfusion. Stroke internists should play the coordinator for the comprehensive assessment of the patients with systemic vascular disease with the various medical specialists, to establish the treatment strategy and management of patients with carotid artery disease.

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I have performed consecutive 220 operations of carotid endarterectomy (CEA) with a fixed team for these 20 years, and reviewed surgical outcome and long term follow-up results.
We have routinely used a shunt system and intraoperative monitoring under general anesthesia. The patients were followed up for 6.5 years on average, and activity of daily life (ADL) was evaluated. Four patients (2.0%) showed neurological deficits after operation, however, all were seen in the initial period of more than 10 years ago. Mortality was 0%. This data is superior to the results of NASCET and ACAS.
One hundred and sixty patients were followed up for more than 1 year. Four patients had re-stenosis of the operated internal carotid artery, and 2 of them underwent CEA again, while asymptomatic period. Four patients had ischemic attack in the operated side but with intracranial lesions. Aggravation of ADL was recognized in 28 patients without carotid lesions. There were 19 deaths, 10 of which were caused by cancers. Twenty seven patients had ischemic heart diseases, and 6 of them died. CEA is effective for prevention of cerebral infarction, when practiced surgeons perform with a shunt system and intraoperative monitoring. However, general examination and treatment with cardiologists are necessary to detect ischemic heart diseases.

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The aim of this prospective multicenter trial was to determine whether bypass surgery can prevent stroke recurrence in patients with major cerebral artery occlusive diseases and hemodynamic cerebral ischemia determined by quantitative measurement of cerebral blood flow, and whether improvement in hemodynamic cerebral ischemia by bypass surgery can prevent the progression of neuropsychological disorders or improve neuropsychological function. The subjects of this study were 206 patients who have been listed for 39 months from November 1st 1998 to March 31st 2002. Each patient underwent treatment according to the study program, and the 2-year follow-up survey of the patients is now underway. Of 206 patients listed in the study, 103 and 103 were assigned the medically-treated group and the surgically-treated group, respectively. Fifteen patients in the medically-treated group and six in the surgically-treated group reached primary endpoint. The incidence of stroke recurrence in the surgically-treated group was significantly lower than that in the medically-treated group (p=0.046). The final results will come out in March 2004.

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Through many experimental brain ischemia studies, it has been suggested that all of the cellular elements in the central nervous system show dynamic stress responses depending on the degree of environmental changes induced by ischemia and reperfusion. In this symposium, first I reviewed the pathogenic role of microvascular stasis (i. e., secondary ischemia) caused by the primary ischemic event and demonstrated the important role of cell adhesion molecules through the experiments using ICAM-1 knock-out mouse as a model of brain ischemia/reperfusion. Next, I discussed the ischemia-induced neuronal cell responses in relation to the apoptosis-like selective neuronal death and the induction of adopted stress responses including stress protein synthesis and 'ischemic tolerance' phenomenon. A variety of stress proteins induced by ischemic stress have been reviewed in relation to their pathophysiological roles in the ischemic brain. Finally, I reviewed the important pathogenic roles of endoplasmic reticulum (ER) stress as well as adaptive responses of ubiquitin-proteasome system in ischemia-induced neuronal cell death. For the development of a novel therapeutic agent against ischemic stroke, it is quite important to clarify both the negative and positive cellular responses induced by brain ischemia/reperfusion.

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Purpose: Thrombolytic therapy has emerged as a new treatment option in the hyperacute stage of ischemic stroke. Although a 15% increase in meaningful rccovery has been observed at three months, it can also trigger devastating hemorrhagic transformations. Therefore, it is important to select suitable patients to undergo this treatment. The purpose of the present study was to evaluate the feasibility of cerebral blood flow (CBF) measurement by xenon-enhanced CT (Xe-CT) in patients with acute ischemic stroke as well as its potential in identifying the occluded artery and the stroke subtype. In effect, this study examines the potential for Xe-CT to select the appropriate candidates for thrombolytic therapy.
Methods : In 36 sequential patients (average age: 64.1 ± 13.1) with sudden-onset of ischemic stroke (except for lacunar stroke) who had presented to our hospital within two hours after the onset, we performed Xe-CT and MRI diffusion-weighted imaging (DWI). A selective cerebral angiography was also done if further evaluation was warranted. We examined the sensitivity of Xe-CT in demonstrating the ischemic area compared with that of DWI, its potential to identify the stroke subtype, its ability to determine infarction and hemorrhage based on CBF thresholds, and its contribution to selection of thrombolysis candidates.
Results: Xe-CT was completed safely in 31 out of 34 patients (91%). Within three hours after symptom onset, Xe-CT detected the ischemic area in most of the patients (94%), whereas DWI failed to do so in 24%. Of 14 patients who underwent both Xe-CT and angiography, the diagnosis of the stroke subtype determined by Xe-CT was confirmed to be correct by angiography in 11 patients (79%). The CBF threshold of nonhemorrhagic infarction in the gray matter became constant (19ml/100g/min) at 3-5 hours after the onset. In hemorrhagic infarction, however, the threshold was initially found to be lower (9ml/100g/min) at 3-5 hours and reaching comparable levels with non-hemorrhagic subtypes (17ml/100g/min) at 5-6 hours. Fourteen patients (39%) were excluded from participation in angiography or subsequent thrombolysis because of their Xe-CT findings.
Conclusion: This study found that Xe-CT was feasible in patients with hyperacute ischemic stroke and more sensitive than DWI in detecting the ischemic area. Moreover, Xe-CT provided crucial information including the stroke subtype and residual CBF in the ischemic territory. Therefore, CBF measurement by Xe-CT may be useful in the patient selection criteria for thrombolytic therapy in the hyperacute phase.

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Clinical pictures of cardioembolic brain infarction (CEBI) are the most serious among ischemic stroke subtypes. Patients with CEBI associated with nonvalvular atrial fibrillation (NVAF) are dramatically increasing in Japan. We aimed to clarify the current status of CEBI in Japan.
We participated in nation-wide, prospective registration studies for acute stroke, Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC; Chief T. Yamaguchi) and Japanese Standard Stroke Registration Study (JSSRS; Chief S. Kobayashi). We analyzed clinical pictures and management in patients with CEBI admitted to the hospitals within the first 7 days and registered to the studies.
The results were almost consistent between the studies. CEBI accounted for 20% (J-MUSIC) or 27% (JSSRS) of acute ischemic stroke. The most frequent cause was NVAF. Both NIH Stroke Scale (NIHSS) and modified Rankin Scale (m-RS) scores in CEBI were the highest among ischemic stroke subtypes. In JSSRS, a multivariate analysis demonstrated that old age, high NIHSS score on admission, hemorrhagic transformation, recurrent stroke during hospitalization, and management without thrombolytic therapy were significant predictors for dependent outcome and death.
It is desired to establish the optimal treatment strategies against CEBI. They include primary prevention, hyperacute interventions such as thombolytic therapy, and measures avoiding early recurrence and symptomatic intracranial hemorrhage.

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In this report, I reviewed lireratures and our clinical experiences of surgical revascularization ; carotid endarterectomy (CEA), intracranial embolectomy, and EC-IC bypass on emergency basis after ischemic cerebral stroke. Especially, in the cases with symptomatic and critical stenosis/complete occlusion of the internal carotid artery (ICA), current topics about efficacy and treatment algolism of emergency or ultra-emergency CEA in this clinical category. In summary ; 1) Crescendo TIAs and stroke in evolution are characteristic symptoms of the critical ICA stenosis and these cases will be absolute indication for emergency CEA. Significance of these symptoms should be more emphasized for early diagnosis in this clinical category. 2) Ultra-emergency thrombolysis and CEA should be the only successful procedure in the serious ICA occlusion group. Proper and quick examination system for true diagnosis, especially for evaluation of effectiveness and risk of surgical revascularization, must be considered.

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