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We report flow characteristics of an in-situ internal thoracic artery (LITA) graft with angiographically competitive flow to the left anterior descending artery (LAD), based upon intraoperative transit-time flow measurement (TTFM) during coronary artery bypass grafting with aortic valve replacement (AVR) and during re-AVR seven years later. Although intraoperative TTFM of the graft showed lower mean flow and higher pulsatility index, suggesting inadequate anastomosis, fast Fourier transform (FFT) analysis of TTFM waveforms presented gradual waning of the amplitude, as shown in patent grafts. FFT analysis of the TTFM waveforms is helpful to judge the patency of LITA to LAD, even with competitive flow. The internal thoracic artery (LITA) graft to left anterior descending artery (LAD) with angiographically competitive flow shows gradual waning of the amplitude on fast Fourier transform (FFT) analysis of the transit-time flow measurement (TTFM) waveforms, although lower mean graft flow, higher pulsatility index, and higher systolic reversal flow may suggest inadequate anastomosis. FFT analysis of the TTFM waveforms is useful to judge the patency of LITA to LAD, even with competitive flow. [ABSTRACT FROM AUTHOR]

We report a case of cardiac recovery from coronavirus disease 2019 (COVID-19)-associated fulminant myocarditis in a 48-year-old woman diagnosed with COVID-19 infection 4 days before, whose hemodynamic collapse were resuscitated first with venoarterial extracorporeal membranous oxygenation, followed by escalation to extracorporeal biventricular assist devices (ex-BiVAD) using two centrifugal pumps and an oxygenator. She was likely to be multisystem inflammatory syndrome in adults (MIS-A) negative. Cardiac contractility gradually recovered after the 9th day of ex-BiVAD support, and the patient was successfully weaned from ex-BiVAD on the 12th day of support. Due to postresuscitation encephalopathy, she was transferred to the referral hospital for rehabilitation with recovered cardiac function. The histopathology of the myocardial tissue showed smaller amounts of lymphocytes and more infiltration of macrophages. It is important to recognize two phenotypes of MIS-A+ or MIS-A−, with distinct manifestations and outcomes. It is also important to refer urgently such patients with COVID-19-associated fulminant myocarditis, showing different histopathology from usual viral myocarditis, with evolution toward refractory cardiogenic shock to a center with capability for advanced mechanical support to avoid a too-late cannulation. We should recognize the clinical course and histopathology of the multisystem inflammatory syndrome in adults phenotype of coronavirus disease 2019-associated fulminant myocarditis. We should urgently refer such patients with evolution toward refractory cardiogenic shock to a center with capability for advanced mechanical support, such as venoarterial extracorporeal membrane oxygenation, Impella (Abiomed, Danvers, MA, USA), and extracorporeal biventricular assist devices. [ABSTRACT FROM AUTHOR]

We report a case of surgically repaired symptomatic mitral valve regurgitation (MR) in a 61-year-old woman with anomalous unilateral single pulmonary vein. A two-staged surgery was scheduled; first a catheter embolization of anomalous vessel to avoid recirculation of the blood into the left atrium during cardiopulmonary bypass, and second a mitral valve repair via right lateral thoracotomy. Scimitar sign is a horn-like shape on plain chest radiograph. One of the possible diagnoses is partial anomalous pulmonary venous return (APVR), which often requires surgical interventions due to comorbidities of congenital heart disease and recurrent pneumonia [1–3]. Another is anomalous unilateral single pulmonary vein (AUSPV), which is generally asymptomatic, and therefore, requires no medical interventions. This case addresses the advantage of multidetector computed tomography (CT) and the safety of two-staged strategy. [ABSTRACT FROM AUTHOR]

• CSDH associated with dural metastasis leads to early recurrence and death. • The prevalence was 16.1% among CSDH patients with active cancer. • Dura mater/subdural hematoma biopsies may be considered in CSDH with active cancer. • Withdrawal of active treatment and change to palliative care may be considered. The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis. [ABSTRACT FROM AUTHOR]

• During short-term electrocardiographic monitoring, atrial fibrillation (AF) was newly diagnosed in 38% patients with suspected embolic stroke of undetermined source. • Decreased left atrial (LA) pump function was strongly correlated with the paroxysmal AF. • Patients with impaired LA function should be carefully monitored to find AF. In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission. Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF. We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p -values <0.05). LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF. [Display omitted] [ABSTRACT FROM AUTHOR]

• About 30% of stroke survivors have some obstacles to walking even in chronic phase. • Robot rehabilitation has attracted attention for the last several decades. • The long-term HAL training improves gait function in stroke patients over a year. Using a robot for gait training in stroke patients has attracted attention for the last several decades. Previous studies reported positive effects of robot rehabilitation on gait function in the short term. However, the long-term effects of robot rehabilitation for stroke patients are still unclear. The purpose of the present study was to investigate the long-term effects of periodic gait training using the Hybrid Assistive Limb (HAL) on gait function in chronic stroke patients. Seven chronic stroke patients performed 8 gait training sessions using the HAL 3 times every few months. The maximal 10-m walk test and the 2-minute walking distance (2MWD) were measured before the first intervention and after the first, second, and third interventions. Gait speed, stride length, and cadence were calculated from the 10-m walk test. Repeated one-way analysis of variance showed a significant main effect on evaluation time of gait speed (F = 7.69, p < 0.01), 2MWD (F = 7.52, p < 0.01), stride length (F = 5.24, p < 0.01), and cadence (F = 8.43, p < 0.01). The effect sizes after the first, second, and third interventions compared to pre-intervention in gait speed (d = 0.39, 0.52, and 0.59) and 2MWD (d = 0.35, 0.46, and 0.57) showed a gradual improvement of gait function at every intervention. The results of the present study showed that gait function of chronic stroke patients improved over a year with periodic gait training using the HAL every few months. [ABSTRACT FROM AUTHOR]

We report a case of mechanical prosthetic mitral valve thrombosis in a 52-year-old woman with previous diagnosis of dilated cardiomyopathy, who was supported with advanced mechanical circulatory support after urgent mechanical mitral valve replacement (MVR) and tricuspid annuloplasty. Difficult weaning from cardiopulmonary bypass needed support with veno-arterial extracorporeal membranous oxygenation and Impella (Abiomed Inc, Danvers, MA, USA), so-called ECPELLA. Temporary discontinuation of heparin and massive blood transfusion were necessary due to four times of reoperation for bleeding during ECPELLA support. Poor recovery of cardiac function needed escalation from ECPELLA to extracorporeal biventricular assist device (ex-BiVAD) using two centrifugal pumps on Day 12. After gradual decrease in the left ventricular assist device flow, transesophageal echocardiography and fluoroscopic images revealed the stuck leaflets of the mitral prosthesis. Therefore, the patient underwent re-MVR with a bioprosthesis on Day 18, followed by continued assistance with ex-BiVAD. The patient was finally weaned from ex-BiVAD on Day 28 and was transferred to the referral hospital for rehabilitation. She was alive in good general condition at 2-year follow-up. It is important to balance the effects of anticoagulation on advanced mechanical circulatory support with ECPELLA, against the side effects of bleeding, especially in post-cardiotomy patients with bleeding tendency. < Learning objective: We should recognize the fatal risks of bleeding and thrombosis during advanced mechanical support, including Impella, VA-ECMO, ECPELLA, and ex-BiVAD, especially in the post-cardiotomy setting. We should also understand the choice of mechanical circulatory support, timely escalation to ex-BiVAD to avoid multiorgan failure, the diagnosis of mechanical mitral prosthetic thrombosed valve using echocardiography and fluoroscopy, and mitral valve replacement in the patient supported with ex-BiVAD.> [ABSTRACT FROM AUTHOR]

Transit-time flow measurement (TTFM) is frequently used for intraoperative graft flow analysis during coronary artery bypass grafting (CABG). Although the TTFM results may be influenced by fractional flow reserve (FFR) of the target coronary artery as a determinant of coronary lesion-specific ischemia, the data have been limited. We retrospectively investigated the relationships between the intraoperative TTFM variables and preoperative FFR values of the target coronary arteries in 40 in situ left internal thoracic artery (LITA) grafts to the left anterior descending artery (LAD), which were revealed to be patent on postoperative computed tomographic angiography. The Spearman correlation coefficients of the TTFM variables with FFR were maximum flow, −0.12 (P =.301); minimum flow (Qmin), −0.43 (P =.004); mean flow (Qm), −0.30 (P =.036); pulsatility index, 0.37 (P =.012); diastolic filling, −0.36 (P =.012); percentage insufficiency, 0.45 (P =.002); and fast Fourier transform (FFT) ratio, −0.07 (P =.329). While Min and Qm showed significant negative correlation, the pulsatility index and percentage insufficiency showed significant positive correlation with FFR. Most TTFM variables, including Qm, of the LITA graft to the LAD during CABG are strongly affected by preoperative FFR values. Because the FFT ratio is not influenced by FFR, FFT analysis of the TTFM may be recommend in the case of the in situ LITA graft to the LAD with moderate stenosis with a higher FFR exceeding 0.75. [ABSTRACT FROM AUTHOR]

• We investigated the effects of action observation treatment (AOT) on gait ability. • The effect of AOT was investigated in patients with subacute to convalescent stroke. • AOT had no effect in patients who could not walk independently. • AOT improved gait ability in patients who were able to walk independently. • AOT may be an effective therapy for patients with stroke who can walk independently. The aim of this study was to investigate the effects of action observation treatment (AOT) on gait ability in patients with subacute to convalescent stroke. Sixteen patients with subacute stroke were divided into a control group (n = 8) and AOT group (n = 8) when admitted to the convalescent ward. The control group received a conventional rehabilitation only. In addition to conventional rehabilitation, the AOT received AOT for 3 months (30 min per day 5 times per week). The AOT involved observing the action of another subject in a comfortable gait situation from the front, sides, and back via video and conducting the actual action. All participants were assessed during the main-assessment period, which included a baseline (i.e., when admitted to the convalescent ward) and 1, 2, and 3 months after baseline. The sub-assessment period at 2 and 3 months after baseline was conducted with participants who could walk independently. The main outcomes of the main-assessment and sub-assessment periods were Functional Ambulation Classification (FAC) and the 10-m walk test (10MWT), respectively. With respect to the FAC, we used a split plot design analysis of covariance to test the interaction between assessment time and group. There was no significant interaction between assessment time and group in FAC. However, a significant improvement of the 10MWT in the sub-assessment period was observed in the AOT group, but not the control group. Our results indicate that AOT may be an effective therapy for patients with subacute to convalescent stroke who can walk independently. [ABSTRACT FROM AUTHOR]

• PCA involvement in unilateral MMD occurs exclusively ipsilateral to the anterior lesion. • The homozygous p.R4810K mutation shows the significant effect on PCA involvement. • Clinical outcome of patients with unilateral MMD is generally favorable. • Dyslipidemia and hypertension are independently associated with any residual symptoms. • Cerebral infarction, confounded by hypertension, is associated with any residual symptoms. The characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. We analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. Among the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. Our findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD. [ABSTRACT FROM AUTHOR]

• Cone beam CTA via intravenous contrast injection might be easy to perform. • Cone beam CTA could be reliable to evaluate patients with ELVO. • Collaterals on cone beam CTA might be a predictor of prognosis after thrombectomy. Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients due to emergent large vessel occlusion (ELVO) is standard treatment, the benefits, however, are highly time-sensitive. After patient eligibility for reperfusion therapy is determined by conventional radiological examinations, the time to be transferred from the department of radiological examination to angiography-suites is critical. We speculated that the time required for the diagnosis of AIS might be reduced if we could determine MT eligibility in patients with ELVO at angiography-suites. Modern angiography-suites with flat panel detectors can perform cone beam (CB)-CT. We performed CB-CTA using intravenous injection of contrast agent to evaluate occlusion sites, collateral score, and construction of vessels distal to occlusion sites and determined if CB-CTA could be useful to evaluate patients with ELVO. We included 15 patients with ELVO diagnosed by conventional MRI or CT/CTA, and investigated whether CB-CTA was reliable to diagnose occlusion sites. We also studied if collateral score on CB-CTA was associated with prognosis after successful reperfusion by MT by comparison between favorable (modified Rankin scale (mRS) 0–2), and unfavorable outcome group (mRS 3–6). There was strong agreement of occlusion sites between CB-CTA and conventional radiological examination (κ = 0.80). Collateral score determined by CB-CTA was significantly different between favorable outcome and unfavorable outcome group (median collateral score 2.3 v.s. 1.3, p = 0.040). Although prospective study of AIS patients at a radiography department is indispensable, CB-CTA performed in an angiography-suite might be useful to evaluate patients with ELVO. [ABSTRACT FROM AUTHOR]

Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is technically demanding. We tried to identify the predictors for short- and long-term outcomes after PEA for CTEPH with aggressive use of pulmonary vasodilators, including epoprostenol sodium. From 2005 to 2013, 122 CTEPH patients, whose preoperative mean pulmonary artery pressure (mPAP) was 47 ± 10 mm Hg and pulmonary vascular resistance was 847 ± 373 dynes/s/cm5, underwent PEA with hypothermic circulatory arrest. Before PEA, all patients underwent pulmonary vasodilator therapy, including epoprostenol sodium of 2 to 6 ng/kg/min. We collected the perioperative and follow-up data retrospectively to identify the predictors for early and late outcomes after PEA. In-hospital mortality was 7.4% (n = 9). Predictors for in-hospital death were age older than 65 years and New York Heart Association Functional Classification IV. Among the 113 PEA survivors, the mPAP and pulmonary vascular resistance significantly decreased. After the median follow-up of 6.8 years, the overall survival rates were 91.8%, 89.2%, 89.2%, 89.2%, and 86.1%, and the cardiac events-free rates were 100%, 98.1%, 95.8%, 85.5%, and 49.0%, at 1, 3, 5, 7, and 10 years, respectively, in the Kaplan-Meier model. A multivariate Cox proportional hazard model identified postoperative mPAP exceeding 30 mm Hg as the only predictor for late cardiac events. Early and late outcomes of PEA for CTEPH with perioperative aggressive pulmonary vasodilator treatment seem satisfactory. However, residual pulmonary hypertension remains challenging to achieve further improvement of late outcomes. [ABSTRACT FROM AUTHOR]

Background: Mechanical thrombectomy undoubtedly improves functional outcomes for patients with acute ischemic stroke. Although we have observed occlusion sites that protrude proximally into the vessel on angiography, termed the "claw sign," we have been unable to state its clinical significance. In this study, we aimed to determine whether the presence of a claw sign was related to recanalization success after mechanical thrombectomy.Materials and Methods: We retrospectively included 73 consecutive patients treated for acute cerebral large vessel occlusion by mechanical thrombectomy between January 2014 and December 2017. The angiographic claw sign was defined as a thrombus that protruded proximally by more than half the diameter of the parent artery. Claw sign positivity, clinical and etiological features, and outcomes were compared between groups with and without recanalization.Results: The claw sign was observed in 29 of 73 (40%) patients and was positive significantly more frequently in those with recanalization (50.0%) than in those without recanalization (5.9%) (P < .01). By multivariate analysis, the claw sign was the only pretreatment parameter to predict successful recanalization (odds ratio, 12.50; 95% confidence interval, 1.50-103.00; P = .019).Conclusions: The presence of the claw sign might predict successful recanalization in patients undergoing mechanical thrombectomy for large vessel occlusion. [ABSTRACT FROM AUTHOR]

Highlights • We investigated activation of mirror neuron system during gait observation. • Participants were sub-acute stroke patients and healthy persons. • Activation of the mirror neuron system was observed in those participants. • Gait observation treatment may improve gait ability in sub-acute stroke patients. Abstract The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH) remains a significant cause of mortality in Japan. The Japan Stroke Society set out to conduct a nationwide survey to identify contributing factors and outcomes of SAH misdiagnosis.Methods: We initially surveyed 737 training institutes and 1259 departments in Japan between April 2012 and March 2014 for the presence of misdiagnosed SAH. Clinical information was then sought from respondents with a positive misdiagnosis. Information on 579 misdiagnosed cases was collected.Results: Most initial misdiagnoses occurred in nonteaching hospitals (72%). Of those presenting with headache, 55% did not undergo a computed tomography (CT) scan. In addition, SAH was missed in the patients who underwent CT scans. The clinically diagnosed rerupture rate was 27%. Mortality among all cases was 11%. Institutes achieving a final diagnosis were staffed by neurologists or neurosurgeons. Multivariate logistic regression analysis indicated that age (≥65), consciousness level (Japan Coma Scale score at correct diagnosis), rerupture of an aneurysm, and no treatment by clipping or coiling were significantly associated with poor clinical outcome.Conclusions: The prognosis of misdiagnosis of SAH is severe. Neuroradiological assessment and correct diagnosis can prevent SAH misdiagnosis. When there is a possible diagnosis of SAH, consultation with a specialist is important. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the effectiveness of genetic testing for the p.R4810K variant (rs112735431) of the Mysterin/RNF213 gene, which is associated with moyamoya disease and other intracranial vascular diseases, in the family members of patients with moyamoya disease.Methods: We performed genotyping of the RNF213 p.R4810K polymorphism and magnetic resonance angiography on 59 relatives of 18 index patients with moyamoya disease. Nineteen individuals had follow-up magnetic resonance angiography with a mean follow-up period of 7.2 years.Results: Six of the 34 individuals with the GA genotype (heterozygotes for p.R4810K) showed intracranial steno-occlusive lesions in the magnetic resonance angiography, whereas none of the 25 individuals with the GG genotype (wild type) showed any abnormalities. Follow-up magnetic resonance angiography revealed de novo lesions in 2 and disease progression in 1 of the 11 individuals with the GA genotype, despite none of the 8 individuals with the GG genotype showing any changes. Accordingly, 8 individuals had steno-occlusive lesions at the last follow-up, and all had the p.R4810K risk variant. The prevalence of steno-occlusive intracranial arterial diseases in family members with the p.R4810K variant was 23.5% (95% confidence interval: 9.27%-37.78%), which was significantly higher than in those without the variant (0%, P = .0160).Conclusions: Genotyping of the p.R4810K missense variant is useful for identifying individuals with an elevated risk for steno-occlusive intracranial arterial diseases in the family members of patients with moyamoya disease. [ABSTRACT FROM AUTHOR]

Background: Quasi-moyamoya disease is an angiographical moyamoya disease equivalent accompanied by known underlying diseases. Mysterin/RNF213 is a major susceptibility gene for moyamoya disease, of which the p.R4810K variant is a founder polymorphism. The genetics of quasi-moyamoya disease is poorly understood, therefore, this study investigated a potential association between the p.R4810K polymorphism and quasi-moyamoya disease.Methods: Genotyping of the p.R4810K variant was performed on 18 quasi-moyamoya disease cases and 91 controls, who visited Kyoto University Hospital or Kobe City Medical Center, Japan, between 2006 and 2015.Results: The p.R4810K variant was found in 12 of 18 quasi-moyamoya disease patients. The frequency of p.R4810K carriers was significantly higher in quasi-moyamoya disease cases than in controls (66.7% versus 2.2%, odds ratio 89.0, 95% confidence interval: 19.2-669.4).Conclusions: Our data showed that the RNF213 p.R4810K polymorphism was significantly associated with quasi-moyamoya disease. [ABSTRACT FROM AUTHOR]

Background Transient neurological deficits are relatively common after direct revascularization surgery for moyamoya disease (MMD). Although recent evidence has revealed the clinical features and pathophysiology, preoperative predictors have remained unclear. This study investigated whether the apparent diffusion coefficient (ADC) in normal-appearing white matter (NAWM) on magnetic resonance imaging could offer a predictor of postoperative transient neurological deficits. Methods This study included adult patients with MMD who underwent superficial temporal artery-middle cerebral artery bypass. Preoperative ADCs were measured in NAWM on ipsilateral hemisphere. Single photon emission computed tomography (SPECT) with 123 I-iodoamphetamine was performed on postoperative days 2-6. Relationships between mean ADC and postoperative transient neurological deficits were assessed. Results Twenty of the 26 subjects (76.9%) experienced transient neurological deficits. Focal hyperemia on postoperative SPECT appeared in 11 of the 20 subjects with postoperative transient neurological deficits and 1 of the 6 subjects without ( P = .12). Mean ADCs in patients with and without postoperative transient neurological deficits were 748.3 ± 12 mm 2 /second × 10 −6 and 679.7 ± 21.9 mm 2 /second × 10 −6 , respectively ( P = .0091). Conclusions Preoperative ADC elevation in NAWM may indicate postoperative transient neurological deficits not only in patients with postoperative hyperemia on SPECT, but also in patients with this pathology. [ABSTRACT FROM AUTHOR]

Background Neurocognitive impairment is one of several unsolved social issues faced by patients with moyamoya disease. Although efforts have been made to investigate cognitive function using neuropsychologic tasks, generalizability has been limited. Here, in a preliminary study, we used structured neuropsychologic tasks to establish a standardized neuropsychologic assessment for adult moyamoya patients with and without difficulty in social independence. Methods Ten patients with neuroradiologically confirmed adult moyamoya disease (3 male, 7 female) participated. Half of all subjects did not have difficulty with social independence (group 1) and the others had (group 2). Group differences were evaluated after basic cognitive abilities and frontal lobe function were tested. Results Although the mean age of group 1 was substantially higher than that of group 2, disease duration did not differ significantly between groups. Means scores for intelligence functions including all subtests for basic cognitive abilities were higher in group 1 compared with group 2. Scores from only 2 frontal lobe evaluation tasks (Trail Making Test B and Theory of Mind) were significantly different between groups. Conclusions This preliminary study provides a profile of neurocognitive dysfunction in adult patients with moyamoya disease using structured neuropsychologic tasks. A broad range of cognitive functions was disrupted particularly in the patients who had difficulty with social independence. To obtain stronger evidence regarding neurocognitive dysfunction in patients with moyamoya disease, a multicenter prospective study is essential. [ABSTRACT FROM AUTHOR]

Abstract: Treatment with DAPT, an inhibitor of the Notch-activating enzyme, γ-secretase is known to reduce damage to ischemic brain. However, the molecular mechanisms supporting this therapeutic effect are not fully understood. Here we demonstrated that Notch/RBP-J signaling is activated in NG2+ glial progenitors and reactive astrocytes such as GFAP+ cells, Nestin+ cells and RC2+ cells, using Notch/RBP-J signaling reporter mice. 3-day DAPT treatment reduced the number of reactive astrocytes but not NG2+ glial progenitors. BrdU labeling experiments have shown that this reduction was due to decreased proliferation of reactive astrocytes. DAPT inhibited nuclear-translocation of Olig2, which is indispensable for proliferation and differentiation of reactive astrocytes. These findings suggest that Notch signaling might promote proliferation and differentiation of reactive astrocytes through the regulation of nucleo-cytoplasmic translocation of Olig2. [Copyright &y& Elsevier]

Objective: Cerebral arteriovenous malformations (AVMs) do not seem to be static congenital vascular malformations but rather are dynamically changing pathologies. In this work, we investigated the expression and possible activation of different signal transducers and activators of transcription (STAT) family members in AVM nidus. Methods: Immunohistochemical analysis was conducted on 25 AVM specimens from 24 patients using antibodies against STATs 1, 3, 5, and 6 as well as their phosphorylated forms. Analysis was also undertaken to determine if there is any correlation between STAT activation and different clinical parameters of AVM patients. Results: Our studies revealed that both STATs 1 and 3 were highly expressed in cerebral AVM, mainly in the endothelium of AVM blood vessels and perivascular infiltrating inflammatory cells within the nidus. STAT3 showed the most intense level of expression within the endothelium and perivascular infiltrating inflammatory cells. It was intensely expressed in the endothelium of 25 (100%) specimens and in the infiltrating inflammatory cells of 24 (96%) specimens. The expression of the phospho-STATs 1 and 3 was also high in the endothelium and perivascular infiltrating inflammatory cells indicating activation of STATs 1 and 3 in AVM. We could not find any significant effect of hemorrhage or preoperative embolization, or other clinical parameters, on the activation of STATs 1 and 3 in cerebral AVMs. Conclusion: We obtained evidence for significant overexpression and activation of both STATs 1 and 3 in cerebral AVM, thus suggesting an important role for these proteins in mediating the pathophysiology of cerebral AVM. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. Background: Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. Methods: Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. Results: Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (−6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p < 0.001) over time between the pitavastatin and diet groups were highly significant. Conclusions: Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes. [Copyright &y& Elsevier]

Background: Sixty-four-slice multidetector computed tomography (64-MDCT) has been shown to be a feasible modality for diagnosing coronary artery disease. We studied the accuracy of 64-MDCT in the detection of diseased grafts and also evaluated its limitations. Methods: This study comprised 19 patients who underwent coronary artery bypass grafting and both invasive coronary angiography (ICA) and 64-MDCT. The 64-MDCT images were analyzed for bypass graft occlusion and significant stenosis (>50%) of the anastomosis, and the results were compared with those of ICA. Results: A total of 90 anastomoses, including 25 proximal anastomoses, were evaluated. Of 65 distal anastomoses, including 5 previously occluded grafts in redo cases, 12 distal anastomoses were identified by 64-MDCT as occluded. In comparison, only 10 grafts were identified as occluded by ICA. The sensitivity, specificity, positive predictive value, and negative predictive value for patency were 100% (10 of 10), 96.5% (55 of 57), 83.3% (10 of 12), and 100% (55 of 55), respectively. The ICA patent grafts were evaluated with respect to stenosis. Invasive coronary angiography identified significant stenosis at only 1 site, whereas 64-MDCT showed significant stenosis at 6 sites. The sensitivity, specificity, positive predictive value, and negative predictive value for stenoses were 100% (1 of 1), 93.1% (67 of 72), 16.7% (1 of 6), and 100% (67 of 67), respectively. Conclusions: Although 64-MDCT demonstrated diagnostic accuracy in evaluating bypass grafts, limitations of this method include false positive results in cases of competitive flow between the graft and the native coronary artery. [Copyright &y& Elsevier]

Abstract: Background: Regrowth of cerebral AVMs after angiographically documented obliteration has been observed in children. In addition, AVMs in adults are reported to be at risk of regrowth despite an angiogram confirming complete removal. However, the mechanism by which regrowth occurs has not been clarified; neither is it clear when regrowth occurs after removal. Case Description: We report 3 cases showing regrowth of AVMs on postoperative angiogram performed 3 months after surgery. We also analyzed the protein levels of various factors that may influence AVM regrowth. Using immunohistochemistry, we analyzed the protein levels of the following factors: CD31 (PECAM), CD34, and CD105 (endoglin), which are endothelial or endothelial progenitor markers; VEGF, a growth factor that may influence AVM regrowth; and PCNA, a marker of proliferating cells. In addition, we analyzed the level of pERK. Conclusion: We report 3 cases of early regrowth of cerebral AVMs. In recurrent AVM samples obtained at second operations, increased levels of perivascular CD105 and pERK immunoreactivity were seen. [Copyright &y& Elsevier]

Abstract: Background: The aim of this study was to compare the effects of inhalation anesthesia with sevoflurane and intravenous anesthesia with propofol on ICP and rCoBF during revascularization surgery for patients with MMD. Methods: Between 1999 and 2004, a total of 90 revascularization surgeries were performed on 58 patients. Among them, in 20 consecutive operations on 14 patients, continuous monitoring of ICP was performed with an ICP monitoring probe. Subsequently, in 14 consecutive operations on 9 patients (CoBF group), intraoperative monitoring of rCoBF was carried out with a laser Doppler flowmeter probe. The monitoring of ICP and rCoBF was performed for more than 20 minutes after the administration of anesthetic was changed from 1.5% to 2.5% sevoflurane to 6 mg/kg per hour of propofol. In all cases, the Paco 2 of these patients was strictly maintained between 38 and 40 mm Hg throughout the operations. Results: In both the ICP and the CoBF groups, the values of physiologic parameters obtained under inhalation anesthesia did not differ statistically from those obtained under intravenous anesthesia. The value for ICP under anesthesia with propofol was significantly lower than that under anesthesia with sevoflurane (P < .0001). The value for rCoBF in the frontal lobe under anesthesia with propofol was significantly higher than that under anesthesia with sevoflurane. Conclusions: Intravenous anesthesia with propofol has potential to provide brain protection and preservation of rCBF in the frontal lobes in surgery for MMD. Whether choice of anesthetic agents might be important in surgery for MMD should be investigated further. [Copyright &y& Elsevier]

Introduction: Urinary titin is a biomarker of muscle atrophy, which is a serious complication after stroke. However, there are currently no clinical data regarding urinary titin in stroke patients.Methods: Consecutive stroke patients admitted to the stroke care unit were included. Spot urine samples were collected immediately after admission, and on days 3, 5, and 7. The primary outcome was the trend of urinary titin in patients after acute stroke. The secondary outcomes included the association between the peak urinary titin level and the modified Rankin Scale (mRS) score, the National Institutes of Health Stroke Scale (NIHSS) score, and the Barthel index (BI) upon hospital discharge. Multivariate analysis was adjusted for age, sex, NIHSS at admission, and the peak urinary titin to predict poor outcome (mRS 3-6).Results: Forty-one patients were included (29 male; age, 68 ± 15 years), 29 had ischemic stroke, 8 had intracerebral hemorrhage, and 4 had subarachnoid hemorrhage. The levels of urinary titin on days 1, 3, 5, and 7 were 9.9 (4.7-21.1), 16.2 (8.6-22.0), 8.9 (4.8-15.2), and 8.7 (3.6-16.2) pmol/mg Cr, respectively. The peak urinary titin level was associated with the mRS score (r = 0.55, p < 0.01), the NIHSS score (r = 0.72, p < 0.01), and the BI (r = -0.59, p < 0.01) upon hospital discharge. In multivariate analysis, the peak urinary titin was associated with poor outcome (p = 0.03).Conclusions: Urinary titin rapidly increased after stroke and was associated with impaired functional outcomes at hospital discharge. [ABSTRACT FROM AUTHOR]

Background. Of 41 patients who had undergone a left-sided simple maze procedure, 4 (9.8%) developed repetitive tachycardia due to atrial flutter, and required radiofrequency catheter ablation. Linear ablation of the right atrial isthmus was effective to treat atrial flutter.Methods. We conducted an electrophysiologic study of atrial flutter and determined its reentry circuit on the atrium. We consider how to reduce atrial flutter after the left-sided simple maze procedure.Results. Common atrial flutter through the right atrial isthmus was induced in all 4 patients, and linear ablation on the right atrial isthmus was effective in 3 of these. An incisional atrial flutter around the right atriotomy was also induced in 2 of 4 patients; both were successfully treated by linear ablation between the right atriotomy and the inferior vena cava.Conclusions. Common atrial flutter through the right atrial isthmus is a risk after the left-sided simple maze procedure. When a left-sided simple maze procedure is performed, sufficient cryoablation on the right atrial isthmus of the arrested heart should be administered to prevent postoperative atrial flutter. [Copyright &y& Elsevier]

Aortic annular rupture is a potentially fatal complication after transcatheter aortic valve implantation with high mortality. Although it is quite rare and difficult to identify the mechanisms and predictors, prosthesis oversizing and massive calcification of the aortic annulus are thought to be a potential risk of this complication. A case presented here is an aortic annular rupture after transcatheter aortic valve implantation. Although the valve was not oversized, there were 2 severe calcifications of aortic annulus at nearby areas like “twin icicles,” thought to be a trigger of this potentially fatal complication. [ABSTRACT FROM AUTHOR]

Background Sox17 has emerged as an important factor in vascular remodeling because of the potential linkage with Wnt/β-catenin, Notch, and the inflammatory pathway. Brain arteriovenous malformation (BAVM), as an angiogenic and inflammatory disorder, might possess an aberrant regulation of the Sox17 associated pathway. We sought to investigate the expression of the Sox17 associated pathway in BAVMs. Methods Using immunohistochemical methods, 16 paraffin specimens of BAVM nidus were analyzed. Specimens were obtained from patients during surgical procedures. Results Expression of Sox17, Hey1, and β-catenin was observed in all specimens. Large veins possessed a distinct pattern of expression; thick-walled veins had a stronger intensity, whereas thin-walled veins had a weaker intensity, of Sox17, Hey1, and β-catenin ( P < 0.001). Thick-walled veins also had a higher expression of Sox17, Hey1, and β-catenin compared with large arteries ( P < 0.05). Hey1 and β-catenin expression was also higher in thick-walled veins compared with brain microvessels ( P < 0.01). In addition, the difference in expression of the Sox17 associated pathway (Hey1 and β-catenin) was observed in medium and small arteries compared with large arteries in BAVM nidus and brain microvessels ( P < 0.01). Conclusions The Sox17 associated pathway was activated in the BAVM nidus. Our results indicate that arterial identity is gained in thick-walled veins; this might reflect the process of arterialization of the veins as a result of hemodynamic stress. In addition, high expression of the Sox17 associated pathway in medium and small arteries indicates that BAVM vessels are intrinsically active. [ABSTRACT FROM AUTHOR]

An understanding of the complex morphology of an arteriovenous malformation (AVM) is important for successful resection. We have previously reported the utility of intra-arterial indocyanine green (ICG) videoangiography for this purpose, but that method cannot detect the angioarchitecture covered by brain tissue. 3-dimensional (3D) multimodal fusion imaging is reportedly useful for this same purpose, but cannot always visualize the exact angioarchitecture due to poor source images and processing techniques. This study examined the results of utilizing both techniques in patients with AVMs. Both techniques were applied in 12 patients with AVMs. Both images were compared with surgical views and evaluated by surgeons. Although evaluations for identifying superficial feeders by ICG videoangiography were high in all cases, the more complicated the AVM, the lower the evaluation by 3D multimodal fusion imaging. Conversely, evaluation of the estimated range of the nidus was high in all cases by 3D multimodal fusion imaging, but low in all but one case by ICG videoangiography. Nidus flow reduction was recognized by Flow 800 analysis obtained after ICG videoangiography. These results showed that utilizing both techniques together was more useful than each modality alone in AVM surgery. This was particularly effective in identifying superficial feeders and estimating the range of the nidus. This technique is expected to offer an optimal tool for AVM surgery. [ABSTRACT FROM AUTHOR]

Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs. We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients. Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus. Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs. [ABSTRACT FROM AUTHOR]