Search

To investigate the associations of perioperative P2Y12 reaction units (PRU) measured using VerifyNow with ischemic and bleeding events, and to determine the PRU threshold in the setting of elective neuro-endovascular treatment (EVT) for intracranial/extracranial vascular disease in patients taking aspirin and clopidogrel.Of the patients undergoing elective neuro-EVT while taking aspirin and clopidogrel, those taking both antiplatelet agents for 7 days or more and whose PRU and aspirin reaction units (ARU) were measured were included. The primary and safety outcomes were defined as symptomatic ischemic and major bleeding events within 30 days after EVT.A total of 197 patients were available for the analyses. Higher PRU was associated with symptomatic ischemic events on multivariable logistic analysis (odds ratio per 10 increase 1.14 [95% confidence interval 1.03-1.27], p=0.011). Receiver operating characteristic curve analysis showed that PRU ≥212 was the threshold to predict symptomatic ischemic events (area under the curve=0.73; sensitivity, 62.5%; specificity, 82.0%). Lower PRU was also associated with major bleeding events (odds ratio per 10 increase 0.87 [0.78-0.96], p=0.004), and the threshold to predict major bleeding events was PRU ≤46 (area under the curve=0.76; sensitivity, 70.0%; specificity, 87.2%) CONCLUSIONS: The PRU value was associated with symptomatic ischemic and major bleeding events after elective neuro-EVT in patients taking aspirin and clopidogrel. PRU ≥212 and PRU ≤46 appeared to be the threshold values to predict symptomatic ischemic and major bleeding events, respectively.

To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke. This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months. A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5–8.48) and in the ADAPT group it was 1.35 (0.37–4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37–0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups. In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

Many neuroendovascular treatments are supported by real-time anatomical and visual hemodynamic assessments through digital subtraction angiography (DSA). Here we used DSA in a single-center prospective randomized crossover study to assess the intracranial hemodynamics of patients undergoing coiling for cerebral aneurysm (n = 15) during sevoflurane- and propofol-based anesthesia. Color-coded DSA was used to define time to peak density of contrast medium (TTP) at several intravascular regions of interest (ROIs). Travel time at a particular ROI was defined as the TTP at the selected ROI minus TTP at baseline position on the internal carotid artery (ICA). Travel time at the jugular bulb on the anterior–posterior view was defined as the cerebral circulation time (CCT), which was divided into four segmental circulation times: ICA, middle cerebral artery (MCA), microvessel, and sinus. When bispectral index values were kept between 40 and 60, CCT (median [interquartile range]) was 10.91 (9.65–11.98) s under propofol-based anesthesia compared with 8.78 (8.32–9.45) s under sevoflurane-based anesthesia (P

A sacral dural arteriovenous fistula (dAVF) is extremely rare, and the pathophysiological and clinical features have not been established. A 70-year-old man developed gradually progressive right-dominant bilateral sensory disorder of the lower limbs. His clinical course and electrophysiological findings were similar to those of multiple mononeuropathy. However, angiography showed a sacral dAVF at the right intervertebral foramen between the fifth lumbar and first sacral vertebrae. Endovascular embolization of the dAVF improved his clinical symptoms and electrophysiological findings. A sacral dAVF can mimic multiple mononeuropathy in terms of its clinical features and electrophysiological findings. A sacral dAVF is a treatable disease and should be considered as a differential diagnosis of lower extremity disorders.

In-stent stenosis (ISS) triggered by a metal-induced allergic reaction of Pipeline embolization device (PED) placement is extremely rare. The present report describes a patient who presented with delayed parent artery occlusion and refractory ISS after PED placement due to cobalt allergy. A patient in her 70s underwent PED placement for a right internal carotid artery (ICA) large aneurysm; 4 months later, the patient presented with left-sided hemiparesis, and MRI revealed right ICA occlusion even though antiplatelet therapy was optimal. She underwent mechanical thrombectomy, and successful recanalization was achieved. However, follow-up angiography 6 months after the thrombectomy revealed severe ISS, and the patch testing showed a positive reaction for cobalt. As a result of long-term administration of oral steroids and antihistamine, progression of ISS was suppressed. It was supposed that a delayed hypersensitivity reaction to cobalt might induce refractory ISS after PED placement.

Graves’ disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of

Importance Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. Objective To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. Design, Setting, and Participants Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. Interventions Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). Main Outcomes and Measures The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. Results Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, −11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞];P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, –0.8% [95% CI, –9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43];P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, –16.8% [95% CI, –32.1% to –1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88];P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, –1.8% [95% CI, –9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24];P = .78). Conclusions and Relevance Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. Trial Registration umin.ac.jp/ctr Identifier:UMIN000021488

Rationale Bridging therapy with endovascular therapy (EVT) and intravenous thrombolysis (IVT) has been reported to improve outcomes for acute stroke patients with large-vessel occlusion in the anterior circulation. While the IVT may increase the reperfusion rate, the risk of hemorrhagic complications increases. Whether EVT without IVT (direct EVT) is equally effective as bridging therapy in acute stroke remains unclear. Aim This randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator for acute stroke with ICA and M1 occlusion aims to clarify the efficacy and safety of direct EVT compared with bridging therapy. Methods and design This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-endpoint clinical trial. The target patient number is 200, comprising 100 patients receiving direct EVT and 100 receiving bridging therapy. Study outcome The primary efficacy endpoint is a modified Rankin Scale score of 0–2 at 90 days. Safety outcome measures are any intracranial hemorrhage at 24 h. Discussion This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities. Trial registration UMIN000021488.

Background Oral function deteriorates easily during the acute phase of cerebral stroke. Therefore, oral health care involving a transdisciplinary approach consisting of dental and medical professionals might be important, but has not been studied in detail. Objective This study assessed the oral health status of patients with cerebral stroke in the acute phase, with the aim of elucidating the efficacy of collaborative, transdisciplinary oral health care involving dentists, dental hygienists, nurses and speech therapists. Methods The participants were 115 consecutive acute cerebral stroke patients, who received oral health care while hospitalised at the university hospital. Their oral health status was assessed using the oral health assessment tool (OHAT) on admission and discharge. Results Patients with acute cerebral stroke had high OHAT scores on admission, meaning poor oral health status. The collaborative oral health care resulted in significant decrease of OHAT scores at discharge, indicative of the improvement of oral health status. Multivariate analysis identified OHAT score for tongue, dentures and oral cleanliness on admission as the significant variables associated with poor oral health status at discharge. Conclusions Thus, the oral health of cerebral stroke patients in the acute phase can be improved by implementing transdisciplinary collaboration of medical and dental professionals. Particularly, patients with problems pertaining to the tongue, dentures and oral cleanliness as revealed through OHAT on admission may require more intensive intervention.

We describe the case of a 75-year-old man with pharyngeal hemorrhage caused by a pseudoaneurysm of the lingual artery after accidentally swallowing his dentures. He developed sudden oral and nasal hemorrhage and was transported to a hospital near his residence. The doctors at the hospital diagnosed the case as epistaxis and treated the symptom with nasal packing. However, the bleeding did not stop and his blood pressure decreased. He was then transported to our hospital. We assumed that the bleeding was caused by epistaxis from branches of the internal maxillary artery, and tried to stop bleeding with the endovascular treatment using coils or liquid embolus materials. Angiography showed a pseudoaneurysm of the lingual artery. Coil embolization against the artery was effective in controlling bleeding. Correct diagnosis and appropriate treatments based on the correct diagnosis are essential in this case of swallowed dentures and bleeding of pseudoaneurysm of the lingual artery.

The effectiveness of thrombectomy for acute ischemic stroke has been established, and earlier treatment produces better outcomes. If possible to identify large-vessel occlusion (LVO) at the prehospital phase, eligible patients can be shipped directly to a hospital that can perform thrombectomy. The purpose of this study was to determine factors that are specific to LVO and can be known before hospital arrival.The subjects were stroke patients during the period between July 2014 and June 2016, who had a National Institutes of Health Stroke Scale (NIHSS) score of 8 or higher and came to our hospital within 6 hours of onset. These patients were divided into an LVO group and a non-LVO group, and background factors, mode of onset, individual NIHSS item scores, and blood pressure at the time of the visit were retrospectively investigated. The selected factors were compared with LVO prediction scales reported in the past.There were 196 stroke patients who had NIHSS scores of 8 or higher and arrived at the hospital within 6 hours. Of these 196 patients, 56 had LVO. This LVO group included a significantly higher number of patients with the 2 items of atrial fibrillation (odds ratio [OR], 11.5: 95% confidence interval [CI], 4.04-32.9; P .0001) and systolic blood pressure of 170 mm Hg or lower (OR, 2.99: 95% CI, 1.33-6.71, P = .008). These 2 items predicted LVO equally to existing LVO prediction scales.The 2 items of atrial fibrillation and systolic blood pressure of 170 mm Hg or lower were significantly correlated with LVO.

The options for treating stroke are limited, but stem cells hold promise as a therapy because of their multipotency. Neuronal cells derived from mesenchymal stem cells (MSC) were reported to have more therapeutic effect than MSCs. For elucidating the therapeutic mechanism of neuronal cells, here we generated a model of focal cerebral infarction by performing left common carotid artery occlusion in adult gerbils. We transfected human trabecular bone-derived MSCs (hMSCs) with the Notch intracellular domain to induce their differentiation into neuronal cells (hN-MSCs). These cells were stereotaxically transplanted into the local ischemic hemisphere 4 days after the occlusion. Behavioral analyses were conducted 28 days after transplantation, and then fluorescence in situ hybridization (FISH) and a histological evaluation were performed. Histologically, transplanted cells were distributed around the periinfarct region, and approximately 8.5% and 4.2% of hN-MSCs and hMSCs survived, respectively; 53.2% ± 9.6% of hN-MSCs were microtubule-associated protein 2(+) (MAP-2(+) ) and extended neurites, whereas only 0.9% ± 0.3% of hMSCs were MAP-2(+) . In FISH, human nucleus-specific signals were detected in both hN-MSCs and hMSCs grafted brains, but no transplanted cell had a merged gerbil-specific nuclear signals. hN-MSC-transplanted animals showed significantly better recovery than animals given control vehicle in the T-maze, bilateral asymmetry, and open field tests. These findings suggested that hN-MSCs have greater therapeutic potential than hMSCs for stroke and that cell fusion does not primarily contribute to the therapeutic mechanism of MSC transplantation.

X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by hypodontia, hypotrichosis, and hypohidrosis, is caused by mutations in ED1, the gene encoding ectodysplasin-A (EDA). This protein belongs to the tumor necrosis factor ligand superfamily. We analyzed ED1 in two Japanese patients with XLHED. In patient 1, we identified a 4-nucleotide insertion, c.119-120insTGTG, in exon 1, which led to a frameshift mutation starting from that point (p.L40fsX100). The patient's mother was heterozygous for this mutation. In patient 2, we identified a novel missense mutation, c.1141G>C, in exon 9, which led to a substitution of glycine with arginine in the TNFL domain of EDA (p.G381R). This patient's mother and siblings showed neither symptoms nor ED1 mutations, so this mutation was believed to be a de novo mutation in maternal germline cells. According to molecular simulation analysis of protein structure and electrostatic surface, p.G381R increases the distance between K375 in monomer A and K327 in monomer B, which suggests an alteration of overall structure of EDA. Thus, we identified two novel mutations, p.L40fsX100 and p.G381R, in ED1 of two XLHED patients. Simulation analysis suggested that the p.G381R mutation hampers binding of EDA to its receptor via alteration of overall EDA structure.

A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine.

BACKGROUND AND PURPOSE: Predicting response to rtPA is essential in the era of endovascular therapy for stroke. The purpose of this study was to elucidate prognostic factors of early neurologic improvement and long-term outcome with respect to the development and reversion of leptomeningeal collaterals in recanalization therapy after acute ischemic stroke. MATERIALS AND METHODS: We analyzed consecutive patients with proximal MCA occlusion treated with rtPA from 2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain MR imaging before rtPA. To assess the reversion of collateral signs, we included patients who underwent follow-up MR imaging. We assessed the development and reversion of collaterals by using a combination of 2 MR imaging collateral markers, the hyperintense vessel sign and the posterior cerebral artery laterality sign. Early neurologic improvement was defined as a decrease in the NIHSS score of ≥10 or a score of ≤2 at 24 hours of treatment. RESULTS: Early neurologic improvement was observed in 22 of 48 eligible patients. The development of collaterals at arrival (15/22 versus 9/26, P = .042) was significantly associated with early neurologic improvement. Multivariate analysis adjusting for other variables showed that the development of collaterals at arrival (OR, 4.82; 95% CI, 1.34–19.98; P = .015) was independently associated with early neurologic improvement. Reversion of collaterals was significantly associated with successful recanalization (P < .001), and multivariate analysis showed that the reversion of collaterals was an independent prognostic factor of long-term functional outcome (OR, 5.07; 95% CI, 1.38–22.09; P = .013). CONCLUSIONS: Our results indicate that the development of leptomeningeal collaterals plays a crucial role in achieving early neurologic improvement, and reversion of collaterals predicts a favorable outcome via arterial recanalization after rtPA treatment for acute stroke.

This paper shows guidelines for the treatment of Crohn's disease in children by the Working Group of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (Chair: Yuichiro Yamashiro) and the Japanese Society for Pediatric Inflammatory Bowel Disease (Chair: Akio Kobayashi). The points in which these guidelines differ from those for adult patients are as follows. (i) Total enteral nutrition in the form of an elemental formula is indicated as primary therapy for children with Crohn's disease at onset as well as the active stage. Oral mesalazine is used together. (ii) Total parenteral nutrition (TPN) with oral mesalazine is required for children with serious illness. The use of a corticosteroid should be withheld for at least 1 week after TPN has been started. (iii) When TPN is not considered to be effective, additional corticosteroid is used. Full doses of corticosteroid should be used for at least 2 weeks after clinical improvement has been achieved, and then the dose of the corticosteroid should be tapered carefully. (iv) When surgery is indicated in pediatric patients with stricture or fistula formation and complicated by persistent growth failure despite medical therapy, the optimum time for surgery is thought to be before epiphyseal plates have been closed.

This paper proposes an optical deflector using an arrayed waveguide with a staircase-like refractive index profile. This device is an optical deflector using an array waveguide with the refractive index different in each of the component waveguides. Optical deflection is accomplished by application of a voltage. In order to study the deflection properties, a theoretical analysis of the structure, device parameters, deflection angle, and number of resolution points is carried out. As a method of realizing an arrayed waveguide with built-in refractive index steps, selective organometallic vapor phase epitaxial growth is used for fabrication of an array waveguide with multiple quantum well structures. Initial experimental results are reported here. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 1–9, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10103

We report the wavelength control of the arrayed waveguide using MOVPE selective area growth. The asymmetric mask pattern, which placed the wide mask next to the one-side-arrayed waveguide, resulted in the gradient change of the bandgap wavelength in array waveguides. The wavelength in each waveguide was found to be linearly changed and clearly dependent on the wide mask width W w . A 100 nm photoluminescence peak wavelength shift in the arrayed waveguide was achieved for a 50 μm asymmetric mask pattern, while maintaining linearly shifted profiles.

Iodide transport defect (ITD) is a rare disorder causing congenital hypothyroidism. We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the prevalence of this mutation, artificial substitution introducing PCR followed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated families with ITD, one patient with low thyroidal 99mTc pertechnetate (99mTcO4−) uptake and 52 healthy controls (104 alleles) were analyzed for this mutation. All families with ITD harbored the mutation, suggesting that T354P is a recurrent mutation and a major cause of ITD. This was not a widespread mutation, because it was not detected in the 52 unrelated normal controls. Because two cases with homozygous T354P mutation developed multinodular goiters within their second decade of life though they had been maintained in euthyroid state, homozygous T354P mutation alone and/or low intrathyroidal iod...

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.

A 54-year-old man developed apathy and memory impairment in 3 months. MRI showed bilateral thalamic hyperintensities with dilated cortical veins in the right cerebellum. Angiography revealed dural arteriovenous fistula (dAVF) at right transverse-sigmoid sinuses with retrograde flow through the vein of Galen (figure 1). Transvenous coil embolization improved his MRI findings (figure 2) and Wechsler Memory Scale–Revised scores from 55 at baseline to 105 in the delayed recall index.

We thank Gomez-Choco et al1 for the interest in our work and their comments on our recently published article about posterior cerebral artery (PCA) laterality sign on 3-dimensional time-of-flight MR angiography.2 In this study, we showed PCA laterality, an indirect radiological marker of collateralization via leptomeningeal anastomoses after middle cerebral artery (MCA) occlusion, was associated with better clinical and radiological outcome in recombinant tissue-type plasminogen activator–treated patients with stroke. To assess the collateral development, Kim et al3 pointed out that the …

We measured the maximal velocity of the blood flow in the main portal trunk by duplex Doppler ultrasound in children suffering from a variety of liver diseases. The maximal velocity of the main portal vein in children with chronic active hepatitis and liver cirrhosis was decreased significantly as compared to those in control children (p < 0.01). The maximal velocity of the main portal trunk and K indocyanine green (ICG) had no significant correlation (r = 0.25, n = 27). The patient with the lowest portal velocity had esophageal and gastric varices with red color sign. We conclude that the measurement of the maximal velocity of the main portal trunk with duplex Doppler ultrasound is useful in evaluating portal hypertension in children.

Background and Purpose— Prominent posterior cerebral artery (PCA) laterality upon 3-dimensional time-of-flight magnetic resonance angiography is often encountered in patients with middle cerebral artery occlusion. We hypothesized that this sign is correlated with improved functional outcome in patients with middle cerebral artery occlusion treated with intravenous recombinant tissue plasminogen activator. Methods— Fifty acute ischemic stroke patients with middle cerebral artery occlusion were treated with intravenous recombinant tissue plasminogen activator from April 2007 to October 2009. All patients routinely underwent initial (first 3 hours) magnetic resonance scans on admission, and additional follow-up (14–21 days after stroke onset) computed tomography scans. Two film readers blinded to all clinical information assessed the presence or absence of PCA laterality on magnetic resonance angiography. We retrospectively analyzed the clinical and radiologic data on all patients. Results— Out of 50 patients, 20 showed PCA laterality on magnetic resonance angiography. National Institute of Health Stroke Scale score 7 days after stroke onset was significantly lower ( P =0.007), and infarct volume on follow-up computed tomography was significantly smaller ( P =0.009) in patients with PCA laterality than in patients without this sign. Multivariate logistic regression analyses showed an adjusted odds ratio of 8.49 for a favorable outcome (modified Rankin Scale score 0–1 at 6 months) in patients with PCA laterality (95% CI: 1.82 to 55.8, P =0.005). Conclusions— The presence of PCA laterality on magnetic resonance angiography before intravenous recombinant tissue plasminogen activator can be used as a predictor of favorable functional outcome in patients with middle cerebral artery occlusion, probably due to improvement of recanalization rate.

A 34-year-old man developed fever and headache, followed by finger tremor and gait disturbance, and was admitted to our hospital about two months after onset. Blood tests showed a white blood cell count of 32,600 /μL with an eosinophil count of 22,300 /μL. There was no evidence of allergic drug reaction or parasitic infection. Cerebrospinal fluid examination demonstrated mononuclear pleocytosis without eosinophils or atypical cells. Brain MRI showed symmetric lesions bilaterally in the medial temporal lobe, frontobasal and insular regions and medulla oblongata. Herpes simplex virus-DNA was negative in the cerebrospinal fluid. The patient died about four months after onset. Histopathologically, there was infiltration of T cells, B cells and macrophages throughout the whole brain, but eosinophils or atypical cells were absent. Immunohistochemistry for herpes simplex virus type 1 and human herpesvirus 6 was negative. This case suggests that fatal encephalitis may develop in association with hypereosinophilic syndrome.

We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4-8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.

We sought to establish a mouse model of subcortical ischemic vascular dementia (SIVD) that develops predominant white matter (WM) injury and cognitive dysfunction induced by chronic cerebral hypoperfusion. Adult C57Bl/6 male (n = 48) mice were subjected to bilateral common carotid artery stenosis with external microcoils (inner diameters: 0.16 mm, left; 0.18 mm, right). Mice were categorized according to left-side cerebral blood flow (CBF) value on day 6 into those with severe cerebral hypoperfusion (SCH; n = 16, < 30% of preoperative CBF baseline value) or moderate cerebral hypoperfusion (MCH; n = 21, 30-50% of preoperative value). Another 15 mice were sham operated. Neurological dysfunction was evaluated by Morris water maze, rotating rod, and open field tests. Histopathological examination was performed on day 35 after surgery. MCH animals showed persistent hyperlocomotion with reduced anxiety and spatial reference memory dysfunction. Rarefaction and small necrotic lesions were predominantly confined to the WM, with reactive astrocytosis, microglial infiltration, axonal loss, and myelin disruption, and these changes were dominant on the left side. SCH animals had persistent hyperlocomotion and motor dysfunction, and their ischemic lesions extended from the WM to the hippocampus and cortex. In MCH animals, myelin basic protein and neurofilament fiber densities in the WM were correlated with the time spent in the correct area in the water maze probe trials. Our MCH mouse model with the development of several types of neurological dysfunction with high reproducibility would be useful for investigating the pathomechanisms of WM injury in human SIVD.

Various types of eosinophilic neurons (ENs) are found in the post-ischemic brain. We examined the temporal profile of ENs in the core and peripheral regions of the ischemic cortex, and analyzed the relationship to the expression of various cell death-related factors. Unilateral forebrain ischemia was induced in Mongolian gerbils by transient common carotid artery occlusions, and the brains from 3 h to 2 weeks post-ischemia were prepared for morphometric and immunohistochemical analysis of ENs. ENs with minimally abnormal nuclei and swollen cell bodies appeared at 3 h in the ischemic core and at 12 h in the periphery. In both locations multiple cell death-related factors including calcium, micro-calpain, cathepsin D, 78 kDa glucose-regulated protein (GRP78) and ubiquitin were activated. In the ischemic core, pyknosis and irregularly atrophic cytoplasm peaked at 12 h, which was associated with significant increases in staining for calcium and micro-calpain. ENs with pyknosis and scant cytoplasm peaked at 4 days and were positive for TUNEL and calcium staining. In the ischemic periphery, ENs had slightly atrophic cytoplasm and sequentially developed pyknosis, karyorrhexis and karyolysis over 1 week. These cells were positive for TUNEL and calcium staining. All types of EN were negative for caspase 3. There may be two region-dependent pathways of EN changes in the post-ischemic brain: pyknosis with cytoplasmic shrinkage in the core, and nuclear disintegration with slightly atrophic cytoplasm in the periphery. This difference coordinates different activation patterns of cell death-related factors in ENs.

Approximately 15-20% of patients with Kawasaki disease (KD) are not responsive to high-dose intravenous gammaglobulin (IVIG). We have previously reported a predictive method for identifying IVIG-non-responsive patients (high-risk KD patients). We determined the safety and effectiveness of pulse methylprednisolone with high-dose IVIG (mPSL+IVIG) as a primary treatment for high-risk KD patients. Sixty-two high-risk KD patients were treated with pulse methylprednisolone 30 mg/kg over 2 h, followed by IVIG 2 g/kg over 24 h (mPSL+IVIG group) and were compared with a historical control group of 32 high-risk patients treated with IVIG 2 g/kg alone at the participating hospitals before this study was opened (IVIG group). High-risk patients were identified with at least two of three predictors (C-reactive protein >or=7 mg/dL, total bilirubin >or=0.9 mg/dL or aspartate aminotransferase >or=200 IU/L). Sixty-six percent (95% confidence interval [CI] 54-78%) of patients had a prompt defervescence in the mPSL+IVIG group compared with 44% (95% CI 26-62%) for the IVIG group (p=0.048). Coronary artery lesions were observed in 24.2% (95% CI 13.2-35.2%) and 46.9% (95% CI 28.6-65.2%) of patients in the mPSL+IVIG and IVIG groups, respectively (p=0.025). This is the first report showing that mPSL+IVIG is effective and safe as a primary treatment for high-risk KD patients.

Clinical, laboratory, and echocardiographic data were retrospectively analyzed in 112 patients with acute Kawasaki disease who received high-dose (2 g/kg) intravenous gamma-globulin (IVIG) treatment within 2 days and were compared for those who were responsive and non-responsive to initial IVIG treatment. Coronary arteries adjusted for body surface area (BSA) were evaluated quantitatively by comparison with the mean dimensions for 85 normal control subjects. The incidence of coronary abnormalities was higher in IVIG-non-responsive patients as compared to IVIG-responsive patients (71% versus 5%, p0.0001). Univariate analysis of pre-IVIG data showed that the neutrophil count and serum levels of C-reactive protein (CRP), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH) were significantly higher in IVIG-non-responsive versus responsive patients. Multivariate analysis selected CRP (p=0.009), TB (p0.001), and AST (p=0.002) as independent predictors of non-responsiveness to initial IVIG treatment. By defining predictive values, patients with at least two of three predictors (CRPor=7.0 mg, TBor=0.9 mg, or ASTor=200 IU/L) are considered to be non-responsive to IVIG for acute Kawasaki disease. Alternatively, more intense initial therapy may be a promising therapeutic strategy for patients who are predicted to be IVIG-non-responsive.