The patient was a 78-year-old male admitted for ventriculitis/bacterial meningitis. Cyanosis was noted in a sitting position. SPO₂ was maintained at 90% or higher in recumbency, but it decreased to 60% in a sitting position, although no dyspnea was noted. On thorough examination, the heart was excluded and the foramen ovale was opened by excessively extending and dilating the ascending aorta. When exclusion by the ascending aorta was strengthened in a sitting position, patency of the foramen ovale was promoted, which increased the right-to-left shunt and decreased SPO₂. Based on these findings, the patient was diagnosed with patent foramen ovale-associated platypnea orthodeoxia syndrome (POS), and the patent foramen ovale was suspected of being the route of infection of ventriculitis/bacterial meningitis. Posterior cerebral arterial embolism developed when he was 73 years old, and paradoxical cerebral embolism involving the patent foramen ovale was suspected. We report a case of patent foramen ovale-associated POS diagnosed in a patient admitted for ventriculitis/bacterial meningitis.

View full abstract

A 67-year-old man presented with loss of vision on the left side due to a cerebral infarction caused by an anterior choroidal artery occlusion. The lesion was very small and confined to the right lateral geniculate body and its adjacent structures. A minute neurological and psychological examination performed at 22 months after the episode demonstrated left hemispatial agnosia, constructional disorder and agraphia, the last of which was more severe in Kanji than in Kana. Only a few case reports describe such unilateral spatial neglect due to a lesion mainly on the lateral geniculate body and having only one concomitant constructional disorder and agraphia. The lesions in those reports, however, included the thalamus or occipital lobe, being considerably larger than ours. The unilateral spatial neglect and constructional disorder are likely to have been caused by parietal lobe dysfunction. The agraphia in our case, being unaccompanied by aphasia, seems to be based on the constructional disorder. The blood flow reduction zone, in the SPECT image, extended from the right occipital lobe to a large part of the parietal lobe. It indicated the symptoms were presumably caused by a dysfunction of the right parietal lobe.

View full abstract

We report a case of ischemic stroke during anticoagulant therapy with rivaroxaban who underwent intravenous thrombolysis with rt-PA. A 78-year-old-woman presenting right hemiparesis and motor aphasia was admitted to our hospital. MRI (DWI) showed a hyper-intensity area in the left frontal lobe. Since more than 18 hours had passed after last intake of rivaroxaban and the prothrombin time was 91%, so its blood concentration and anticoagulant effect were assumed low. Therefore rt-PA was administered 3 hours and 40 minutes after the onset. Right hemiparesis was improved and she was discharged with a mild speech disturbance. Safety of rt-PA administration might be assessed by elapsed time from last intake of rivaroxaban.

View full abstract

Fukuoka Stroke Registry (FSR) is a multicenter hospital-based registry. In this cohort, we are collecting the data from acute stroke patients. Kyushu University Hospital and six other stroke centers in Fukuoka participate in this registry. Using FSR data, we are doing risk-related, pathophysiological, and genomics- and proteomics-related studies. In this review, we introduce three recent topics of FSR. First topic is prestroke glycemic control and clinical outcomes of acute stroke patients. In this study, we have shown that poor glycemic control before stroke occurrence may be detrimental to clinical course after onset, and consequently lead to poor functional outcome of ischemic stroke. Second topic is Asian dust and stroke. In this study, we have shown that Asian dust may be specifically associated with the risk of atherothrombotic brain infarction. Last topic is research for biomarkers in ischemic stroke (REBIOS). In this study, we explored stroke-related proteins and investigated the precise functions of the proteins using in vitro and in vivo experiments. For example, we have shown that RANTES, a chemokine, is produced from neurons after ischemic stroke and may have a potential to protect neurons directly or indirectly through the production of neurotrophic factors in peri-infarct areas. Using FSR data and basic research, we are investigating the detailed pathphysiological mechanisms of cerebral ischemia.

View full abstract

The city of Tokyo established the Tokyo Metropolitan Stroke Association Council in April 2008, and began discussions regarding the establishment of an emergency transportation system at that time. As a result, a system was introduced in March 2009 by which cases in which stroke were suspected by emergency and rescue teams were transported to the closest certified Tokyo Metropolitan Acute Stroke Care Facility. A survey was conducted of the total number of patients transported on an emergency basis in one week in the city of Tokyo one year after introduction of the system. The results of that survey verified there were no significant problems with the system with respect to such factors as the sensitivity and specificity of stroke assessment by emergency and rescue teams or the transport status of stroke patients transported to health care facilities by emergency and rescue teams. Within the time elapsed from the beginning of the attack to arrival at the hospital, the amount of time from the attack until the time the patient was discovered (time when an emergency call was made) was clearly determined to be long. Therefore this indicated the need for educational activities for providing residents with information regarding strokes and their symptoms. When a similar survey was conducted two years later, the time from attack to discovery was determined to have become significantly shorter, thereby demonstrating the effectiveness of educational activities deployed during that time. However, there were no significant reductions observed in the amount of time from attack to arrival at the hospital, thereby suggesting the need for actions to be taken to further shorten the amount of time elapsed from discovery to arrival at the hospital.

View full abstract

The prevalence of pediatric stroke is much lower than that of adult stroke. There are two important features in pediatric stroke. One is the pathophysiology of pediatric stroke is different from that of adult stroke. The other is that pediatric stroke has many kinds of causative disorders. According to the data of children hospitalized with stroke in U.S., hemorrhagic stroke comprised 43% of strokes and is more common in the younger children. Ischemic stroke comprised of 57% and is more common in the older children. In this review, we focused on five disorders in pediatric stroke (hemorrhagic stroke in neonate, acute infantile hemiplegia, moyamoya disease, arterial dissection and arteriovenous malformation). We summarized the pathophysiology and treatment of these disorders.

View full abstract

We built the stroke medical treatment network (regional inter-hospital referral model for stroke) by front cooperation with the family medicine and rear cooperation with a rehabilitation specialty hospital. We have reinforced the stability cooperation between specialty hospitals to accept stroke patients without declining them because of minimal staff and for the immediate nature period to utilize local health resource with in-hospital systems construction effectively. We were able to solve many problems by network construction. Furthermore, for the cooperation of convalescence and the maintenance period, the development of the liaison critical pathways for stroke and the construction of the operative network, the establishment of the Kumamoto Zaitaku Doctor Net was performed, and network construction advanced more. As for the horizontal cooperation between Kumamoto city public hospitals, various actions in regional alliances meeting (meeting of the regional alliances room) were established. We became able to analyze much data with the liaison critical pathway by being computerized. We developed construction of the integrated community care system, making and using advanced directives and the stroke notebook for a stroke patient perform self-administration now.

View full abstract

Epidemiological evidence indicates that type 2 diabetes is an independent risk factor for brain infarction. The rate of brain infarction is a two- to three-fold higher in individuals with diabetes than in those without. Diabetes mellitus is associated with all types of infarctions, including lacunar infarction, atherothrombotic brain infarction and cardioembolic brain infarction. Patients with diabetes mellitus tend to experience small- to mid-sized infarcts in the brainstem or vertebrobasilar territories. The role of glycemic control in reducing macrovascular risk has not been established clearly in patients with type 2 diabetes. In the UKPDS trial, treatment with metformin resulted in significant risk reduction with respect to stroke events. A recent meta-analysis of eight phase 3 studies also suggested that linagliptin may have benefits for stroke prevention in patients with type 2 diabetes. In addition, a subanalysis of the PROactive trial, which evaluated patients with a previous history of stroke, showed a significant decrease in the incidence of strokes in the pioglitazone group with a stroke history. However, most randomized clinical trials have not demonstrated beneficial effects of intensive glycemic therapy on macrovascular (particularly stroke) outcomes in type 2 diabetes patients. Beneficial effects have been shown for multifactorial therapy, including controlling dyslipidemia and/or hypertension in addition to the blood glucose level. The Steno-2 and J-EDIT studies reported a reduction in stroke risk among type 2 diabetic patients following multifactorial therapeutic intervention. These findings indicate that the most effective approach for preventing macrovascular complications, including stroke, is multifactorial risk factor reduction (glycemic control, smoking cessation, aggressive blood pressure control, treatment of dyslipidemia and, for secondary prevention, the daily administration of anti-thrombotic agents).

View full abstract

Effects of EPA-E on brain protection were examined using a rat transient focal cerebral ischemia model. Rats were subjected to 90 min ischemia following daily administration of EPA-E (100 mg/kg/day) or vehicle for 7 days. EPA-E treated animals showed reduction in decreased ADC area just prior to reperfusion and infarct volume reduction as well as neurological improvement at 24 and 72 hours after reperfusion. In addition, p-adducin and vWF positive vessel densities, 8-OHdG and 4-HNE positive cells and TUNEL positive cells within the cortical boundary zone were decreased in EPA-E treated animals. Pretreatment with EPA-E for more than 5 days demonstrated infarct volume reduction and neurological improvement, and withdrawal of EPA-E for less than 3 days following 7 day-pretreatment was also neuroprotective. Continuous administration of EPA-E may be important for brain protection, and decrease in endothelial damage, inhibition in Rho-kinase activation and reduction in tissue oxidative stress may be involved in the protective mechanisms of EPA-E.

View full abstract

Chronic kidney disease (CKD) is an independent risk factor for stroke, and it is reported that increase of albuminuria and reduction of estimated glomerular filtration rate (eGFR) cause higher risk of stroke. We examined a characteristic of the ischemic stroke patient with CKD. 62.8% patients had CKD, which defined as albumin-creatinine ratio (ACR) ≥30 mg/gCre or eGFR <60 ml/min/1.73m² or both. Cerebral white matter lesions and carotid artery IMT were advanced in the CKD groups compared with non-CKD group. The neurological severity at admission and discharge was worsened in ACR ≥30 mg/gCre groups. It is proposed that there are several mechanisms which correlate between CKD and stroke, such as risk factors for arteriosclerosis, endothelial dysfunction and similarity of vasculature. The stroke patient with CKD requires medical treatment that is careful to renal function, and is necessary to control a risk factor of arteriosclerosis and a risk factor peculiar to CKD.

View full abstract

Granulocyte-colony stimulating factor (G-CSF: Filgrastim) may be useful for treatment of acute ischemic stroke owing to its neuroprotective and neurogenesis-promoting properties, but excessive increase of neutrophils may lead to brain injury. Here, we examined the safety and tolerability of low-dose G-CSF, and investigated the effectiveness of G-CSF given intravenously in the acute phase (at 24-hour) or sub-acute phase (at 7-day) of ischemic stroke. Leukocyte levels remained below 40,000/μl at 150 and 300 μg G-CSF/body/day, but rose above 40,000/μl at 450 μg G-CSF/body/day. Neurological function improvement between baseline and day 90 was more marked after treatment in the acute phase versus the sub-acute phase (Barthel Index 49.4±28.1 vs 15.0±22.0; p<0.01). Now we have started a phase II study of testing G-CSF, at those two doses and placebo that starts at 24 hours after ischemic stroke onset and continues for five days.

View full abstract

The author presents an overview of the recent advances in antithrombotic therapy for acute ischemic stroke and transient ischemic attack (TIA). First, the Japanese Government approved the 4.5 hour time-window of intravenous recombinant tissue-type plasminogen activator (rt-PA) therapy in August 2012, and the Japan Stroke Society published the 2nd version of the guidelines of rt-PA therapy in October 2012. Second, a randomized controlled trial, CHANCE, performed in China recently demonstrated the efficacy and safety of dual antiplatelets therapy (DAPT) in acute minor stroke or TIA. Many novel anticoagulants, a direct thrombin inhibitor and Xa inhibitors, became available in clinical use for patients with nonvalvular atrial fibrillation. However, the efficacy and safety of NOACs remains unresolved in acute ischemic stroke. A new era has begun in antithrombotic therapy for patients with acute ischemic stroke and TIA, and we will achieve dazzling achievements in near future.

View full abstract

We had demonstrated that intravenous administration of bone marrow-derived mononuclear cells improves functional recovery through enhanced angiogenesis in experimental stroke models. Based on these observations, we have started phase ½, a clinical trial of cell-based therapy for patients with cardiogenic cerebral embolism (ClinicalTrials. gov ID: NCT01028794). Major inclusion criteria is the patient diagnosed with sever cardiogenic cerebral embolism (NIHSS≥10 at day 10 after onset of stroke). Patient has 25 ml (low dose group, n=6) or 50 ml (high dose group, n=6) bone marrow aspiration on day 7–10 after onset of stroke. Autologous bone marrow derived mononuclear cells are purified by density gradient method and administrated intravenously on the day of cell aspiration. Primary endpoint is the safety and improvement of NIHSS, compared with our historical control. We have treated 12 patients and no adverse effects were observed. Most of the patients showed significant improvement of neurological function at 6 months after cell transplantation. Autologous bone marrow mononuclear cells transplantation is likely to be safe, feasible and improve functional recovery.

View full abstract

Neuroprotective therapy with edaravone does not protect only neural cells but also the neurovascular unit as a whole. Therefore, this therapy greatly reduces hemorrhagic transformation under thrombolytic therapy with tPA or endovascular surgery in acute stroke. Recent reports showed an improving recanalization rate in tPA therapy. The neuroprotective drug edaravone is currently used in daily stroke clinics of Japan, China and India. A recent report from Europe displayed similar protective results in their countries with edaravone.

View full abstract

The need for seamless medical care cooperation in cerebral apoplexy inter-regional association and the fees of the medical treatment and nursing-care accompanying cooperation were described. As a tool for smooth cerebral apoplexy inter-regional association, “the note for safe cerebral apoplexy cooperation,” “my chart,” “medicine notebook” and “Medicine and a care inter-regional association critical path” have been used in Kagawa Prefecture. ICT of the community-health-care cooperation in Kagawa Prefecture is a “community-health-care cooperation network,” “Kagawa Medical Internet eXchange,” and “medical care inter-regional association critical path.” This time, the present condition of ICT and its subject were reported.

View full abstract

It has been established by epidemiologic studies that low LDL-cholesterol and high LDL-cholesterol levels are associated with hemorrhagic and ischemic stroke, respectively. Statin treatment has been shown to reduce the risk of stroke by around 20% in both primary and secondary stroke prevention. Beneficial effect of statin was reduction of ischemic stroke and major vascular events. Furthermore, meta-analysis papers showed that LDL lowering with statin has no effect for the risk of intracerebral hemorrhage. Thus aggressive lipid lowering treatment may be recommended in patients with ischemic stroke, but target LDL-cholesterol level has not been established for secondary stroke prevention.

View full abstract

With an appearance of recombinant tissue plasminogen activator (rtPA) and new devises to retrieve a clot, the management of stroke therapy is changing. However, the number of people who can get this benefit is still very few. To establish new brain protective therapy is urgent. In this article we will display our recent trials. We applied a protein transduction technology using the artificial super anti-apoptotic FNK protein fused with a protein-transduction-domain peptide (PTD-FNK), which showed significant reduction of infarct volume. Next was the application of anticonvulsive drug valproic acid (VPA) to cerebral ischemia. Injecting VPA showed significant protective effect by reducing oxidative stress and inflammatory changes.

View full abstract