Background and Purpose: Soluble fibrin monomer complex (SFMC, within normal limit of 3.0 μg/ml) is a sensitive marker for coagulation. We investigated change of plasma levels of the SFMC before and after the introduction of antithrombotic therapy in acute ischemic stroke. Method: We studied 87 patients with acute ischemic stroke and divided them into two groups, 21 patients with cardioembolic stroke who started to receive anticoagulation (CES group), and the other 66 with non-cardioembolic stroke who commenced to have antiplatelet therapy. We measured plasma level of SFMC in the 87 patients before and after commencement of antithrombotic therapy and compared them in the CES and non-CES groups separately. Results: In CES group, the plasma level of SFMC significantly declined after commencement of the treatment (from median 4 μg/ml to median <3.0 μg/ml, p=0.018), while the non-CES group did not demonstrate any significant changes in the level of SFMC (from median <3.0 μg/ml to median <3.0 μg/ml, p=0.175). The rate of SFMC levels more than the upper limit of normal range was significantly reduced after the commencement of the treatment in the CES group (from 57.1% to 14.3%, p=0.004), while it was not in the non-CES group (from 12.1% to 7.6%, p=0.24). Conclusions: It seems that the plasma level of SFMC is a useful indicator for effectiveness of anticoagulation in patients with acute cardioembolic stroke.

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Background and Purpose: There is still a regional difference in the treatment for acute ischemic stroke in Japan. We examined our medical system and results of intravenous recombinant tissue plasminogen activator for this disease at our hospital located in the provinces. Methods: The key of our medical system is the cooperation of physicians and exclusive nurses. We compared neurologic improvement within 24 hours, intracranial hemorrhage within 36 hours, and outcome (mortality and modified Rankin Scale at 3 months) of 14 patients ≥81 years of age with 18 patients ≤80 years of age. Results: Our medical system worked well without problem. There was no difference between the two age groups in the incidence of neurologic improvement, intracerebral hemorrhage, and mortality. The patients ≥81 years of age reduced independence (mRS 0–1, 0% versus 44.4%; p=0.004), however, one-fifth still maintained their ADL (mRS 0–2, 21.4% versus 44.4%; p=0.163). Conclusions: It is important to construct their own medical system. It was suggested that patients ≥81 years of age fulfilling the criteria for intravenous rt-PA can be candidates for this treatment.

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Background and Purpose: The purpose of this study was to evaluate the effects of recombinant tissue plasminogen activator (rt-PA) for mild ischemic stroke (NIHSS ≤ 4) on vascular studies, and to clarify which patients with mild symptoms are candidates for intravenous thrombolysis. Methods: Eighty-three patients with NIHSS scores of 1–4 and whose intracranial vascular study was performed within rt-PA treatable time were selected. The clinical courses of 32 propensity-matched pairs of patients treated with or without intravenous rt-PA thrombolysis were investigated. Results: The NIHSS score change at 24 h and median mRS score at discharge were −1, 1 in the 32 patients with rt-PA, significantly smaller than that in matched patients without thrombolysis (0, 2), respectively. The NIHSS score change at 24 h was significantly smaller in the rt-PA group (−2), than in the non-rt-PA group (0) in patients with vessel stenosis or occlusion. No significant difference in NIHSS score change at 24 h was seen between the rt-PA group (−1) and non-thrombolysis group (0) in patients with no vessel occlusion. Conclusions: Thrombolytic therapy should be considered for cases with mild symptoms (NIHSS ≤ 4) and intracranial vessel stenosis or occlusion.

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Case 1 involved a 77-year-old woman with diabetes mellitus. She was aware of right hemiparesis, and was admitted on the next day. Case 2 involved a 66-year-old man with diabetes mellitus. He was admitted because of the rapid progression of systemic edema, gait disturbance, and dysarthria. Right hemiparesis and sensory disturbance developed 3 days after the admission. Both cases were diagnosed as having nephrotic syndrome with bilateral multiple brain infarction on the initial MRI diffusion-weighted images. In case 1, bilateral vertebral artery stenosis was observed. In both cases, atrial fibrillation was not observed, but left atrial spontaneous echo contrast and aortic arch complicated lesions were revealed in transesophageal echocardiography. Hypercoagulant state due to nephrotic syndrome could be also related with thrombus formation in the atherosclerotic lesion or left atrium, and anticoagulant therapy was continued. In the previous reports of nephrotic syndrome with brain infarction, few cases underwent transesophageal echocardiography (TEE), however, the etiology of their infarction was likely to be embolism in many cases. Left atrial spontaneous echo contrast and aortic arch complicated lesion might be frequent in cases with both nephrotic syndrome and brain infarction especially in the middle-aged and elderly patients, and TEE should be required in such cases.

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An 82-year-old man treated with rivaroxaban 10 mgQD for prevention of stroke associated with nonvalvular atrial fibrillation developed left thalamic hemorrhage with symptoms of consciousness disturbance and right hemiparesis and was transferred to our hospital after about 2 hours and 3 hours of taking tablet, respectively. Head computed tomography (CT) examination demonstrated the left thalamic hemorrhage with size of 10 ml. Immediately, administration of antihypertensive agents was started to keep systolic blood pressure below 140 mmHg and 1,000 IU of prothrombin complex concentrate (PCC) was administered which reversed prothrombin time-international normalized ratio (PT-INR) from 1.33 to 1.14. However, the size of hematoma grew up to be 21 ml and 23 ml after 3 hours and 5 hours after the admission, respectively. It seems that lowering blood pressure and administration of PCC may be ineffective against hematoma expansion in brain hemorrhage occurring within a couple of hours after taking rivaroxaban.

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A 40-year-old housewife had severe anemia (hemoglobin 1.1 g/dl) because of menorrhagia for the past several years. She was admitted to the hospital, and a massive transfusion of packed red blood cells (2,800 ml) was performed. The hemoglobin level improved to 10.7 g/dl. Furthermore, she had undergone a surgery for uterine myoma, which may have caused menorrhagia. Two weeks after the transfusion, she suddenly experienced a severe headache and generalized tonic-clonic seizure. Magnetic resonance imaging (MRI) showed multifocal constriction of cerebral arteries on magnetic resonance angiography (MRA), and bilateral multiple high intense lesions were detected by T₂-weighted imaging. We diagnosed reversible cerebral vasoconstriction syndrome (RCVS) with posterior reversible encephalopathy syndrome (PRES). We treated the patient with a calcium channel blocker and anti-epileptic drugs; the symptoms and MRI findings improved immediately. The symptoms (headache and partial convulsions) and vascular constrictions on MRA worsened, but improved again once the dose of the calcium channel blocker and anti-epileptic drugs were increased. Five weeks after admission, the patient was discharged with no neurological deficits. Several cases of RCVS and PRES after blood transfusion have been reported. Although the mechanisms are unknown, blood transfusion for severe chronic anemia is one of the risk factors of RCVS and PRES. When performing a blood transfusion to severe chronic anemic patients, it is necessary to consider RCVS and PRES if the patient has severe headache, seizures, and other neurological symptoms.

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Having two medical institutes to manage acute stroke victims, we have built a flexible system to exchange patients and information between the two institutes (Hyogo Emergency Medical Center and Kobe Red Cross Hospital) and two departments (the department of emergency medicine and that of neurosurgery). The system is reported here. An interview for 10 emergency physicians about the stroke treatment was conducted to investigate how much the emergency physicians are concerned about stroke and how they think about the system.

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Neural stem cells are now known to persist in the adult mammalian brain, including human brain. This capacity for neurogenesis at the adult stage is associated with self-repair mechanisms in damaged or diseased brains. In addition, several studies have reported a correlation between neurogenesis and functional recovery after brain damage. Then, many studies have been done to promote the regeneration of neurons after brain damage. Intraventricular administration of growth factor is one of the promising approach for such a purpose. Here, we discuss the recent findings we have made about the enhancement of endogenous neurogenesis.

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Cryptogenic stroke is defined as a brain infarction not clearly attributable to a definite cardioembolism, large artery atherosclerosis, small artery disease, or other specific cause of stroke despite extensive investigations. Cryptogenic stroke accounts for 25 (23–40) % of the whole brain infarction. The causes of cryptogenic stroke or embolic stroke of undetermined source (ESUS) are covert paroxysmal atrial fibrillation, patent foramen ovale, aortic plaque, or a cancer. Therefore, it is necessary to perform (1) medical history, particularly the paroxysmal atrial fibrillation; (2) physical and neurological examinations; (3) D-dimer and BNP; (4) 12-lead ECG, Holter ECG, ECG monitor, and longer-time ECG monitor for the detection of covert paroxysmal atrial fibrillation; (5) MRI (detection of the lesion with the diffusion-weighted image, in particular) and MRA; (6) transthoracic echocardiography (TTE) and ultrasonography of cervical arteries; (7) transesophageal echocardiography (TEE) and TCD in bubble study (detection such as the patent foramen ovale); (8) vein echography; and (9) special laboratory testing which included a genetic test and screening for thrombophilic states. The advanced diagnostic techniques such as the cardiac telemonitoring, D-dimer, transesophageal echocardiography, coronary computed tomographic angiography, carotid plaque image, or high-resolution wall MRI are required to identify the cause of cryptogenic stroke.

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According to the findings of the Hisayama Study, an epidemiological study of cardiovascular disease in the general Japanese population, the incidence of ischemic stroke decreased greatly from 1960s to 1990s in men and from 1960s to 1970s in women as a result of the spread of hypertension treatment. However, the decreasing trends in the ischemic stroke incidence are probably due to the increase in the prevalence of metabolic risk factors such as glucose intolerance and hypercholesterolemia. In this review, we evaluated the associations of metabolic risk factors with the risk of stroke using the data from the Hisayama Study. (1) In a 7-year follow-up survey of 2,851 residents of Hisayama town aged 40 to 79 years, elevated hemoglobin (Hb) A1c levels were significantly and linearly associated with an increased risk of developing ischemic stroke. Subjects with HbA1c of 5.5% or higher had a significantly higher risk of ischemic stroke than those with HbA1c of 5.0% or lower, suggesting that elevated HbA1c, even in the prediabetic range, was a significant risk factor for the development of ischemic stroke. (2) A 24-year follow-up study for 2,452 Hisayama residents aged 40 years or over demonstrated that elevated non-high-density lipoprotein cholesterol levels were a significant risk factor for the development of atherothrombotic brain infarction. In conclusion, the intensive management of these metabolic risk factors is needed for further prevention of ischemic stroke in Japanese population.

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Prevalence of chronic kidney disease (CKD) and atrial fibrillation are increasing in step with the aging of the population in Japan. Both of them that link each other are independent risk factors of ischemic stroke, and CKD is also an important risk factor for hemorrhagic stroke. Therefore, controversies still exist as to the indication of anticoagulant therapy for patients with CKD. Safety and value of anticoagulation, especially in patients with advanced stages of CKD, remain to be proven. On the other hand, recent data suggest that patients with non-end stage CKD might take advantage of well-controlled warfarin or novel anticoagulants. Clinicians should ponder indication of anticoagulants for CKD patients and keep an eye on the kidney function during anticoagulant therapy.

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