Alzheimer Dementia Detection Based on Time-series Instability of Heart Rate.

Towards early detection of Alzheimer dementia (AD), this paper focuses on time-series instability of heart rate of AD patient, and proposes the AD detection method based on heart rate acquired by an unconstrained mattress sensor for daily life use. Through the human subject experiments on 124 days of heart rate of one AD patient and 39 days of heart rate of 21 healthy subjects, the following implication have been revealed: (1) an accuracy of the proposed AD detection method based on the time-series features of heart rate is approximately 98%; and (2) the time-series instability of heart rate is found in the rapid oscillation of heart rate (i.e., an increase/decrease of heart rate over 2 seconds).

A pitfall of cognitive bias during the pandemic: Two cases of Plasmodium falciparum malaria coinfected or misdiagnosed with COVID-19.

We report two the cases of patients with imported Plasmodium falciparum malaria during the COVID-19 pandemic. One was coinfected with COVID-19 and the other was misdiagnosed with COVID-19; either way, the diagnosis of malaria was delayed. These cases suggest that physicians should beware of cognitive biases during pandemics and carefully evaluate febrile patients. Malaria should be considered in any febrile patient returning from a malaria-endemic area.

Unstable Circadian Rhythm of Heart Rate of Alzheimer Dementia Based on Biological Data of Mattress Sensor.

It is important to detect daily Alzheimer dementia (AD) possibility using unconstrained mattress sensors because dementia takes time before subjective symptoms appear and the main treatment is to slow the rate of progression. Forcusing on circadian rhythm disorder which tend to occur with AD, this paper analyzes the features of unstable circadian rhythms of heart rate associated with its weakening and misalignment in AD. It is found that the external feature of heart rate of AD that of up and down changes seen frequently compared to that of healthy subjects makes the multiple types of effects on the estimation process of the AD detection method based on the circadian instability represented by the trigonometric regression equation estimated from the heart rate. So, we designed two feature values from the effects and analyzed them in an analysis experiment. An analysis experiment was conducted on the heart rate of total 72 days data of one AD patient and total 30 days data of 21 healthy people, and the result confirmed significant differences between the AD and the healthy people at from 0.01% to 0.1 % level for the first feature and at from 0.1% to 5% level for the second feature. And the result shows the possibility that differences in the heart rate features is found between AD and healthy people.

Non-Contact REM Sleep Estimation Correction by Time-Series Confidence of Predictions: From Binary to Continuous Prediction in Machine Learning for Biological Data.

This paper focuses on the REM sleep estimation with bio-vibration data acquired from mattress sensor, and proposes its "correction" method based on Time-Series Confidence (TSC) of the REM sleep prediction calculated by Random Forest (RF) as one of the Machine Learnings (MLs). Unlike the conventional MLs that classify whether the REM sleep or not as its binary prediction, the proposed method determines whether the estimated REM sleep should be corrected or not from its continuous prediction. Concretely, the proposed method computes the REM sleep prediction as the percentage of trees that classify the REM sleep for each epoch (30 seconds), calculates TSC of the REM sleep prediction by windowing the REM sleep prediction of a certain number of epochs to smooth them, and the REM sleep estimated by other MLs is corrected when TSC is lower than a certain threshold. Through the human subject experiments, the following implications have been revealed: (1) the proposed method shows a small TSC in the sudden wrong REM sleep estimation, which contributes to correct it; and (2) because of this feature of the proposed method, the number of False-Positive of the REM sleep estimation is successfully reduced, which improves Precision from 51.4% (w/o TSC) to 59.4% (w/ TSC).

Distinct roles of HMGB1 in the regulation of P­glycoprotein expression in the liver and kidney of mice with lipopolysaccharide­induced inflammation.

The role of high mobility group box 1 (HMGB1) in the regulation of efflux transporters in the liver and kidney remains unclear, although it has been reported that HMGB1 can increase P­glycoprotein (P­gp) expression in the brain. The present study aimed to clarify the involvement of HMGB1 in the regulation of P­gp expression in the liver and kidney of mice with lipopolysaccharide (LPS)­induced inflammation. Mice were treated with LPS or LPS + glycyrrhizin (GL); GL is as an HMGB1 inhibitor. Subsequently, the expression levels of transporters, such as P­gp, and HMGB1 receptors, such as toll­like receptor (TLR)4 and receptor for advanced glycation end­products (RAGE), were determined by quantitative PCR and LC­MS/MS­based targeted proteomics. For the in vitro study, HepG2 and KMRC­1 cells were used, as was a co­culture of KMRC­1 and differentiated THP­1 cells. The mRNA and protein expression levels of Mdr1a and Tlr4 in the kidneys of LPS + GL­treated mice were significantly decreased compared with those in LPS mice. The results indicated that HMGB1 had little effect on the expression of Mdr1a and Tlr4 in the liver, since there was little change in of Mdr1a and Mdr1b expression between the LPS and LPS + GL­treated mice. Notably, regarding MDR1 mRNA expression, KMRC­1 cells were more responsive to LPS than HepG2 cells, and KMRC­1 cells treated with LPS exhibited increased levels compared with control KMRC­1 cells. In differentiated THP­1 cells, LPS treatment decreased the mRNA expression levels of TLR4, whereas they were restored to control levels by HMGB1. In conclusion, HMGB1 in the plasma and TLR4 in macrophages may be involved in the regulation of P­gp expression in the kidneys of inflamed mice.

Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment.

SLC25A39/40, involved in mitochondrial GSH (mGSH) import from the cytoplasm, is essential for protection against oxidative stress and mitochondrial dysfunction. We examined the effects of cholestasis, through bile duct ligation (BDL) and lipopolysaccharide (LPS)-induced inflammation in mice, on Slc25a39/40 expression. Additionally, we used human clear cell renal carcinoma (KMRC-1) cells to elucidate the mechanism of regulation of SLC25A39/40 expression in the kidneys after LPS treatment. BDL resulted in a decrease in Slc25a39 mRNA in the liver and a decrease in Slc25a39/40 mRNA and protein in the kidneys. Consequently, there was a significant decrease in mGSH levels in the kidneys of BDL mice compared with those in sham mice. LPS treatment resulted in increased Slc25a40 expression in the kidneys. In KMRC-1 cells, the combination treatment of LPS-RS or FPS-ZM1 with LPS suppressed the LPS-induced increase in SLC25A40, suggesting that SLC25A40 expression could be regulated by the signaling pathway via toll-like receptor 4 and the receptor for advanced glycation end products, respectively. Our findings contribute to understanding the role of mGSH in the maintenance of the mitochondrial redox state. To the best of our knowledge, this is the first study that demonstrates the changes in Slc25a39/40 expression in mice with cholestasis-associated renal injury and LPS-induced inflammation.

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

Alzheimer Dementia Detection Based on Unstable Circadian Rhythm Waves Extracted from Heartrate.

This paper proposes the novel Alzheimer dementia (AD) detection method based on unstable circadian rhythm of heartrate acquired from mattress sensor. Concretely, the pro-posed method, UCRADD (Unstable Circadian Rhythm based Alzheimer Dementia Detection), estimates the circadian rhythm of heartrate by calculating the regression of the trigonometric functions with the maximum likelihood estimation, and judges instability of the circadian rhythm by the coefficients of the equation estimated trigonometric functions. Through the human subject experiment with one elderly AD subject in two months (i.e., August and December), three elderly (age from 60-70) non-AD subjects, the ten middle-aged non-AD subjects and eight young non-AD subjects, the following implications have been revealed: (1) UCRADD succeeds to detect the AD patients in the high rate and keeps it in two months (78.9% in August and 82.4% in December), while our previous method cannot keep the rate at the same level in two months (57.9% in August and 82.4% in December). (2) the instability of circadian rhythm of heartrate has the potential of being new symptom of AD.

Increased penetration of diphenhydramine in brain via proton-coupled organic cation antiporter in rats with lipopolysaccharide-induced inflammation.

Uptake transporters in brain microvascular endothelial cells (BMECs) are involved in the penetration of basic (cationic) drugs such as diphenhydramine (DPHM) into the brain. Lipopolysaccharide (LPS)-induced inflammation alters the expression levels and activities of uptake transporters, which change the penetration of DPHM into the brain. A brain microdialysis study showed that the unbound brain-to-plasma partition coefficient (K p,uu,brain) for DPHM in LPS rats was approximately two times higher than that in control rats. The transcellular transport of DPHM to BMECs was increased when BMECs were cultured with serum from LPS rats. Compared with control rats or BMECs, the brain uptake of DPHM in LPS rats was increased and the intracellular accumulation of DPHM was increased under a high intracellular pH in BMECs from LPS rats, respectively. Treatment of BMECs with transporter inhibitors or inflammatory cytokines had little impact on the intracellular accumulation of DPHM in BMECs. This study suggests that LPS-induced inflammation promotes unidentified proton-coupled organic cation (H+/OC) antiporters that improve the penetration of DPHM into rat brain via the blood-brain barrier.

Early diagnosis of Cryptococcus neoformans var. grubii meningitis using multiplex PCR assay in an immunocompetent patient.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

Use of Preprocedural, Multiple Antiplatelet Medications for Coil Embolization of Ruptured Cerebral Aneurysm in the Acute Stage Improved Clinical Outcome and Reduced Thromboembolic Complications without Hemorrhagic Complications.

BACKGROUND: The most uncontrollable complication during coil embolization of a ruptured cerebral aneurysm is thromboembolic ischemia. We analyzed whether thromboembolic complications could be reduced by using preoperative antiplatelet medications for acute subarachnoid hemorrhage in multicenter fashion. METHODS: We selected antiplatelet medicines according to an official protocol: a combination of 200 mg aspirin, 150 or 300 mg clopidogrel, and 200 mg cilostazol. Systemic heparinization was done after sheath insertion in all cases. One hundred and ten consecutive, ruptured cerebral saccular aneurysms that underwent coiling at our institute were analyzed. Procedure-related thrombus formation on digital subtraction angiography and clinical evidence of ischemia and procedure-related stroke on computed tomography scan were reviewed. RESULTS: Eighty cases (73%) were medicated with multiple antiplatelet medications, 22 cases (20%) were treated with a single medication, and 8 cases (7%) were treated without antiplatelet medication. Thromboembolic complications were reduced in an inverse relationship with the number of antiplatelet medications. Hemorrhagic complications because of antiplatelet medications did not occur. Postoperative symptomatic vasospasm tended to decrease, and outcome also tended to improve in the multiple medications groups. Reduction of thromboembolic complications significantly improved clinical outcome in logistic regression analysis. CONCLUSIONS: Preoperative multiple antiplatelet medication reduced thromboembolic events in coiling during acute stage subarachnoid hemorrhage and improved clinical outcomes.

The Effect of Goreisan on the Prevention of Chronic Subdural Hematoma Recurrence: Multi-Center Randomized Controlled Study.

The relatively high rate of post-operative recurrence in the treatment of chronic subdural hematoma (CSDH) is a significant problem. Goreisan is an herbal medicine that exhibits a hydragogue effect by inhibiting the expression of aquaporins, and its efficacy in preventing post-operative CSDH recurrence has been suggested by several case trials. This multi-center prospective randomized controlled trial was performed to investigate the preventative effect of goreisan on post-operative CSDH recurrence. Patients with symptomatic CSDH over 60 years old undergoing burr hole surgery were enrolled in this study. The patients were randomly allocated to the control group or the goreisan group, in which oral administration of goreisan (7.5 g daily) was continued for 12 weeks. The primary end-point was the post-operative recurrence rate at 12 weeks and the secondary end-point was hematoma volume reduction rates on computed tomography scan at 12 weeks. The analyses were performed not only on patients of all ages older than 60 years, but also on patients divided into those over or under 75 years old. One hundred and eighty patients were followed and analyzed (the control group, n = 88; the goreisan group, n = 92). The recurrence rates considering patients of all ages and patients under 75 years old were relatively low in the goreisan group but without a significant difference. The hematoma volume reduction rates showed no significant difference. Based on the results of the present study, a larger-scale study including more cases is necessary in future to confirm the efficacy of goreisan.

Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double-blind, placebo-controlled trial.

Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

Intra-arterial oxidative stress correlates negatively with cognitive function and positively with postoperative ischemic lesions in carotid artery stenosis stenting.

BACKGROUND AND PURPOSE: Carotid plaque contains biologically active substances released into the blood during carotid artery stenting (CAS). The main purpose of this prospective study was to analyse sequential changes in oxidative stress during CAS and their relationship to clinical factors. METHODS: Twenty-two consecutive CAS procedures were performed between May 2014 and April 2016. Arterial blood was collected four times: (1) after the sheath insertion without edaravone; (2) pre-angioplasty with edaravone from the carotid artery; (3) after post-stenting angioplasty from an occluded carotid artery; and (4) before sheath removal. Derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured photometrically. The relationship between d-ROMs or BAP and preoperatively investigated biochemical parameters, cognitive function, and number of diffusion-weighted image (DWI) high spot lesions was analysed using one-way ANOVA and the Tukey-Kramer HSD test. RESULTS: The d-ROM values for CAS were 355±58.8 Carratelli Units at sheath insertion, 315±57.2 after edaravone infusion, 328±56.8 after post-stenting angioplasty, and 315±53.0 just before sheath removal. The d-ROM values were reduced significantly after edaravone infusion (P<0.05). The BAP at sheath insertion was reduced significantly according to age (P<0.05). The d-ROMs at sheath insertion correlated negatively with the dementia scale and positively with the post-CAS DWI high spots (1.00±1.07; P<0.05). Other biochemical parameters did not correlate with the d-ROM values or BAP. CONCLUSION: Oxidative stress is correlated negatively with cognitive function and positively with postoperative ischemic lesions. Antioxidant potential decreases with ageing.

Rehabilitation and the Neural Network After Stroke.

Stroke remains a major cause of disability throughout the world: paralysis, cognitive impairment, aphasia, and so on. Surgical or medical intervention is curative in only a small number of cases. Nearly all stroke cases require rehabilitation. Neurorehabilitation generally improves patient outcome, but it sometimes has no effect or even a mal-influence. The aim of this review is the clarification of the mechanisms of neurorehabilitation. We systematically reviewed recently published articles on neural network remodeling, especially from 2014 to 2016. Finally, we summarize progress in neurorehabilitation and discuss future prospects.

Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily A member 1 in a rabbit model.

BACKGROUND AND AIMS: Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect. METHODS: After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology. RESULTS: Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group. CONCLUSIONS: This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. METHODS: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. RESULTS: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. CONCLUSIONS: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

Analysis of Factors That Influence Long-Term Independent Living for Elderly Subarachnoid Hemorrhage Patients.

BACKGROUND: The number of elderly subarachnoid hemorrhage (SAH) patients has been increasing. The aim of this study was to analyze long-term outcome for elderly (≥75 years) SAH patients and to establish a treatment strategy. METHODS: From January 2005 to December 2013, 86 consecutive cases were treated. We used a modified Rankin Scale (mRS) at the outpatient clinic or a telephone interview of patients and/or families. Kaplan-Meier plots were done for mortality and independent (mRS 0 ∼ 2) state. Multivariate analysis was done to distinguish factors that influence on outcome. RESULTS: Median age was 79, Hunt-Kosnik grade 1 ∼ 3 was 79%, and the radical intervention (clipping or coiling) rate was 78%. Mean follow-up period was 28.7 ± 3.4 standard error months. Half of deaths occurred during the first two months. The number of cases of independent living gradually decreased to 50% at 28 months after SAH. Half of patients lived independently for 36 months at HK grades 1 to 3, and 3 months at HK grades 4 to 5 (p < 0.05). Half of patients lived independently for 40 months in the radical intervention group, and 14 months in the conservative treatment group (p < 0.05). Multivariate analysis for independent living revealed that gender, pre-morbid condition, HK grade, and postoperative complication were significant (p < 0.05). CONCLUSIONS: Good-grade elderly SAH cases that were independent pre-stroke should have radical intervention performed for aneurysm. Avoiding perioperative complications have a positive influence on long-term independent living.

Safety of preprocedural antiplatelet medication in coil embolization of ruptured cerebral aneurysms at the acute stage.

Preoperative antiplatelet medication for aneurysm coil embolization during acute subarachnoid hemorrhage (SAH) is not common. However, recent advances in neurointerventional devices make antiplatelet medication necessary for SAH surgery. We tested the hypothesis that preprocedural antiplatelet therapy in the acute stage of SAH prevents complications due to ischemia or induced bleeding. We retrospectively reviewed 35 consecutive ruptured cerebral saccular aneurysms that underwent coiling at our institute. Two hundred milligrams of aspirin and 150 mg of clopidogrel were administered to the patients at least two hours before coiling. Systemic heparinization was given after sheath insertion. Procedure-related thrombus formation on digital subtraction angiography, and clinical evidence of ischemia and procedure-related stroke on CT were reviewed. The median patient age was 69 years. Five males and 30 females were included. Seventy-seven percent of patients were Hunt-Hess grades 1 to 3. Assist techniques were used in 20 cases (57%). We inserted one extracranial internal carotid artery stent, but no intracranial stent. Intraoperative thrombosis occurred in one case (2.9%), with no clinical symptoms. Postoperative cerebrospinal fluid drainage was done in three cases, but we experienced no bleeding complications. Preoperative antiplatelet therapy leads to a low rate of thromboembolic events in coiling during acute stage SAH, and this strategy had no adverse influence on bleeding complications.

The role of arterioles and the microcirculation in the development of vasospasm after aneurysmal SAH.

Cerebral vasospasm of the major cerebral arteries, which is characterized by angiographic narrowing of those vessels, had been recognized as a main contributor to delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH) patients. However, the CONSCIOUS-1 trial revealed that clazosentan could not improve mortality or clinical outcome in spite of successful reduction of relative risk in angiographic vasospasm. This result indicates that the pathophysiology underlying DCI is multifactorial and that other pathophysiological factors, which are independent of angiographic vasospasm, can contribute to the outcome. Recent studies have focused on microcirculatory disturbance, such as microthrombosis and arteriolar constriction, as a factor affecting cerebral ischemia after SAH. Reports detecting microthrombosis and arteriolar constriction will be reviewed, and the role of the microcirculation on cerebral ischemia during vasospasm after SAH will be discussed.