Several studies have proven the usefulness of thrombolytic agents in the therapy of ischemic stroke. Thrombolysis is an approved and generally recommended treatment for acute stroke within three hours after the onset of symptoms in north America and Europe. However, it has not approved in Japan yet. This update summarizes the current status of two ongoing clinical trials of thrombolytic therapy in Japan; (1) Japan Alteplase Clinical Trial (J-ACT), which is a prospective, open-label trial of intravenous alteplase (0.6mg/kgBW) for all types of ischemic stroke within 3 hours of onset, and (2) Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT Japan), which is a randomized controlled trial of intra-arterial urokinase (<600, 000 IU) for middle cerebral artery occlusion within 6 hours of onset. J-ACT has been completed recently, and suggested that alteplase at the dose of at 0.6mg/kg is effective for Japanese patients with ischemic stroke comparably to that at the dose of 0.9mg/kg in US and Europe. MELT Japan is now ongoing, and the available data in an interim analysis suggests that intra-arterial urokinase is promising.

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Beneficial effects of long-term HMG-CoA reductase inhibitor (statin) treatment for primary and secondary prevention of coronary heart disease (CHD) have been shown in several clinical trials and some of these statin trials in patients with established or high risk for CHD have shown that statins decrease stroke incidence. However, beneficial effects of statin for patients with chronic ischemic stroke and no histry of CHD remains to be clalified. The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Study is a prospectivee randomised, open, blinded endpoint study designed to evaluate the effects of pravastatin 10mg/day in patients who preveously experienced an ischemic stroke other than cardioembolic infarction, but who do not have any CHD requiring statin treatment. We planed to enroll a total of 3, 000 patients, aged 45-80 years whc have serum cholesterol level of 180-240mg/dl. The primary endpoint is fatal and non-fatal stroke recurrence during the follow-up period of 5 year and the data collection phase of the study is expected to be completed by April 2010. Effects of statin on hs-CRP and carotid intima-media thickness will also be investigated as substudies of J-STARS. The detailed process for J-STARS protocol establishment have been presented in this symposium.

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It is unclear whether asymptomatic cerebral infarction (ACI) is associated with an increased risk of stroke. We therefore evaluated the number of ACI, perivascular hyperintensity (PVH) and deep subcortical white matter hyperintensity (DSWMH) on MRI in 468 subjects with ACI, who consist of in healthy elderly persons and in patients with a first stroke. The number of ACI (less than 10mm), perivascular space, the grading of PVH and DSWMH were significantly increased year by year. The grading of PVH was increased only in subjects with hypertension, although the number of ACI was increased in subjects with or without hypertension. No effects of total cholesterol and triglyceride on the number of ACI and the grading of PVH and DSWMH were observed. In subjects with ACI, annual incidence of clinical stroke was significantly higher in patients with a first stroke (6.9%) than in healthy elderly persons (1.7%). Although the number of ACI was significantly aggravated year by year in spite of using hypertensive, hyperlipidemic and anti-platetet agents, the grading of PVH and DSWMH were aggravated only in patients given no medications. These results indicate that the management of risk factors is important for patients with ACI, as same as in patients with stroke.

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We studied incidence, risk factors and prognosis of silent brain infarction (SBI) in more than 3, 000 people who undertook brain check-up since 1988. SBI increases linearly as a function of age after the age of 50s. The most potent risk factor for SBI was a medical history of hypertension (odds ratio = 3.2). Other factors included age, male sex and high level of blood glucose. The risk of symptomatic stroke occurrence was 10 times higher in those with SBI (annual incidence = 2.8%) compared to those without SBI (0.3%). The number of microbleeds in T2 * image was correlated with the number of SBI and was related to blood pressure level. A long-term follow-up study showed that the occurrence of cerebral hemorrhage was not low (22%) in those with SBI, although cerebral infarction was most frequent (66%). The follow-up study also demonstrated that cognitive impairments were associated with the increase of SBI. The cognitive deterioration was more closely related to the worsening of white matter changes, which also had a strong association with hypertension. These results suggest that the management of SBI and its risk factors, especially hypertension, is critical for preventing subsequent stroke occurrence and cognitive deterioration.

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Basic MRI techniques for diagnosis of silent brain infarcts are discussed. Advantages and disadvantages of various basic MR techniques including T1WI, T2WI, FLAIR and PDWI are also evaluated. The use of FLAIR and PDWI is especially suited to differentiate ischemic lesions from CSF-containing spaces such as ventricular system and cerebral sulci. However, surprisingly little is known about the disadvantages of FLAIR. Precise differentiation between complete and incomplete infarct are sometimes difficult on FLAIR especially at the short repetition time. The use of PDWI is suited to this occasion. In conclusion, most useful basic MR imagings for evaluation of silent brain infarcts and white matter lesions are T1WI, T2WI and PDWI. Silent lacunar hemorrhages can be well appreciated on T2 -weighted sequences like gradient-echo.

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At 1997, Alexopoulos and Krishnan coined the term "vascular depression" to describe depression associated with cerebrovascular disease. Vascular depression included both post-stroke depression, depression occurring after a stroke, and MRI-defined vascular depression in which cerebral infarction has been detected by magnetic resonance imaging finding. Post-stroke depression is well known as showing cerebral infarction on imaging modalities as well as clinical symptoms such as localized neurological symptoms related to infarcts. MRI-defined vascular depression demonstrated cerebral infarction on imaging modalities, but there were no clinical symptoms such as localized neurological symptoms or stroke. MRI-defined vascular depression was equivalent to the term "depression with silent cerebral infarction" which we studied in the past decade. When the accumulation of infarct lesions induced obstruction in the neuron network related to mood and will exceeds a certain threshold, the patients becomes predisposed to vascular depression. Neurological factors were more prominent than genetic factors and psychosocial stressors in patients with vascular depression due to an accumulation of infarct lesions.

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The breakthroughs in visualization technology and the intensive research endeavors in molecular biology, hematology, and angiology are gradually disenteangling the complex matter of stroke. Taking into account the fact that by 2020, stroke mortality will have almost doubled, mainly as a result of an increase in the proportion of older people (Ch. Warlow, et al., Lancet, 362, 1211-1224, 2003), emphasis should be placed on the importance of laboratory training and experience to learn microneurosurgical skills and microsurgical techniques, particularly in the field of re-constructive neurovascular surgery. In the future, the indications for reconstructive vascular surgery will become clearer, and the number of cases will increase accordingly. The synchronic expansion of advances in diagnostic techniques with the remarkable evolution in treatment modalities, including the broad spectrum of pharmacologic therapies as well as refined microsurgical techniques, will be outlined.

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A consequence of the continuing development of medical and surgical equipment, the evolution of new neurosurgical methods and the refinement of microneurosurgical techniques, are aspects which require our attention, our concentrated effort and our positive attitude.
Despite the stress of our multi-tasking environment, rewards and satisfaction can be reaped from our participation in the care of neurosurgical patients.

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