[Metabolic insult causing re-expression of old stroke (MICROS) presenting as stroke mimics].

BACKGROUND: Metabolic insult causing re-expression of old stroke (MICROS), one of the stroke mimics, is characterized by reappearance of impairment of past stroke and can be mistaken for a stroke recurrence. The aim of the present study was to identify the clinical characteristics of MICROS in emergency stroke care, and to investigate predictive factors for distinguishing MICROS from stroke recurrences. METHODS: In our Stroke Center, 519 consecutive patients admitted with suspected stroke in June 2016 to December 2017. MICROS was defined as an acute deterioration of neurological deficits of the previous stroke despite no evidence for stroke recurrences. Among the 70 patients with a past history of stroke, 14 were MICROS, 5 were transient ischemic attack, 15 were other stroke mimics, and 36 were stroke recurrences, respectively. We evaluated the clinical characteristics of MICROS and compared MICROS with stroke recurrences. RESULTS: The causes of MICROS were infectious disease (including influenza and pneumonia) in 4, transient somnolence after syncope in 4, hypo/hyperglycemia in 2, medication overdoses in 1, and anxiety in 3. Eight of the 14 MICROS patients were admitted within 4 hours after the symptom onset. In MICROS patients, fever (>37°C) was observed more frequently than those with stroke recurrences though the difference was not statistically significant. CONCLUSION: MICROS might be associated with fever, syncope, or serum glucose abnormality. MICROS patients sometimes visit the hospital emergency room within 4 hours, thus, distinction between MICROS and true stroke recurrences is important.

Comprehensive analysis for viral elements and interleukin-28B polymorphisms in response to pegylated interferon plus ribavirin therapy in hepatitis C virus 1B infection.

UNLABELLED: To comprehensively characterize the contribution of virological factors as well as interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (Peg-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino-acid (aa) sequence study in 103 consecutive HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding-window comparison analysis to characterize response-specific viral sequences, along with IL28B SNP analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), nonearly viral response (nEVR), sustained virological response (SVR), or relapse, the following regions were extracted as most significantly associated with the different responses respectively: nonstructural protein 5A (NS5A) aa.2224-2248 (P = 1.2E-07); core aa.70 (P = 4E-04); NS5A aa.2340-2382 (P = 7.0E-08); and NS5A aa.2360-2377 (P = 1.1E-05). Those NS5A regions nearly coincided with the interferon (IFN) sensitivity-determining region (NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (odds ratio [OR] = 16.8; P = 0.009) and NS5A aa.2340-2382 (OR = 13.8; P = 0.0003) were extracted as the two most-significant independent variables contributing to the final outcome. CONCLUSION: In Peg-IFN/RBV therapy, polymorphisms in IL28B, NS5A aa.2224-2248, core aa.70, and, most important, NS5A aa.2340-2382 have a tremendous influence on treatment response in association with viral kinetics, resulting in significantly different outcomes in chronic HCV-1b infection.

Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients.

BACKGROUND AND AIMS: Protease inhibitor (PI)-resistant hepatitis C virus (HCV) variants may be present in substantial numbers in PI-untreated patients according to recent reports. However, influence of these viruses in the clinical course of chronic hepatitis C has not been well characterized. METHODS: The dominant HCV nonstructural 3 (NS3) amino acid sequences were determined in 261 HCV genotype 1b-infected Japanese patients before pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, and investigated the patients' clinical characteristics as well as treatment responses including sustained virological response (SVR) rate. HCV-NS3 sequences were also determined in 39 non-SVR patients after completion of the therapy. RESULTS: Four single mutations (T54S, Q80K, I153V, and D168E) known to confer PI resistance were found in 35 of 261 patients (13.4%), and double mutations (I153V plus T54S/D168E) were found in 6 patients (2.3%). Responses to PEG-IFN/RBV therapy did not differ between patients with and without PI-resistance mutations (mutation group, SVR 48%; wild-type group, SVR 40%; P = 0.38). On the other hand, two mutations appeared in two non-SVR patients after PEG-IFN/RBV therapy (I153V and E168D, 5.1%). CONCLUSIONS: PI-resistance-associated NS3 mutations exist in a substantial proportion of untreated HCV-1b-infected patients. The impact of these mutations in the treatment of PIs is unclear, but clinicians should pay attention to avoid further development of PI resistance.

Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C.

BACKGROUND AND AIMS: The association between hepatitis C virus (HCV) sequences with interleukin 28B (IL28B) single-nucleotide polymorphism (SNP) in the development of hepatocellular carcinoma (HCC) has not been well clarified. METHODS: Complete HCV open-reading frame sequences were determined in 20 patients developing HCC and 23 non-HCC patients with HCV-1b infection in two distant time points. An additional 230 patients were studied cross-sectionally for core and NS5A sequences with HCC development. Among them, 98 patients with available samples were investigated for changes in viral core sequences over time. Finally, IL28B SNPs and HCC development were investigated in 228 patients. RESULTS: During observation period (HCC for 10.8 years, and non-HCC for 11.1 years), changes in core a.a. 70 and three amino acid positions in NS5A were characteristics of the patients developing HCC. In 230 patients, Q (glutamine) or H (histidine) to R (arginine) ratio at core a.a. 70 was significantly higher in the HCC group (HCC group 43:22 vs. non-HCC group 66:99, p = 0.001). A change in core R70Q was observed over time in 11 patients associated with a decrease in platelets (p = 0.005) and albumin (p = 0.005), while a Q70R change was observed in 4 patients without associated changes in platelets (nonsignificant) and albumin (nonsignificant). IL28B SNP showed significant correlation with the core a.a. 70 residue. There was no evident link between IL28B SNPs and the occurrence of HCC. CONCLUSIONS: Hepatitis C virus core a.a. 70 residue is associated with liver disease progression and is independent factor for HCC development in genotype-1b infection. IL28B SNPs are related to core a.a. 70 residue, but not to HCC. The functional relevance of core a.a. 70 residue in hepatitis C pathogenesis should be further investigated.

Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C.

We report a case of pericarditis and chronic inflammatory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C. The patient developed moderate weakness in the lower limbs and dyspnea. He was hospitalized for congestive heart failure. An electrocardiogram showed gradual ST-segment elevation in leads V(1) through V(6) without coronary artery disease. A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function. Anti-DNA antibody and antids DNA IgM were positive. Neurological examination revealed a symmetrical predominantly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution. Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance.

Detection of hypervascular hepatocellular carcinoma with multidetector-row CT: single arterial-phase imaging with computer-assisted automatic bolus-tracking technique compared with double arterial-phase imaging.

PURPOSE: To compare single arterial-phase (SAP) computed tomography (CT) imaging with bolus tracking (BT) with double arterial-phase (DAP) CT imaging for detecting hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: The DAP images were obtained at 25 (DAP-early) and 40 seconds (DAP-late) after the start of contrast material injection. All patients underwent SAP-BT imaging where images were obtained 10 seconds after the CT attenuation value of the aorta reached the threshold value of 120 Hounsfield unit (HU) in 29 (group 120-HU), 160 HU in 30 (group 160-HU), and 200 HU in 32 patients (group 200-HU). Attenuation conspicuity with SAP-BT technique was compared with that with DAP technique using repeated-measures analysis of variance. Attenuation conspicuity and mean scan delays with SAP-BT images obtained with different threshold values were compared using analysis of variance. The sensitivities were compared using McNemar and Fisher exact tests. RESULTS: Within all groups, mean attenuation conspicuity with SAP-BT and DAP-late was significantly higher than that with DAP-early. Regarding SAP-BT, mean attenuation conspicuity in group 200-HU (42 +/- 18 HU) was significantly higher than those in groups 120-HU (23 +/- 11 HU) and 160-HU (25 +/- 11 HU). Mean scan delays for SAP-BT were 24.2 seconds in group-120 HU, 26.8 seconds in group-160 HU, and 31.1 seconds in group-200 HU (P < 0.001). The mean sensitivity with SAP-BT technique in group 200-HU (92.7%) was significantly higher than those in groups 120-HU (72.4%) and 160-HU (71.1%). CONCLUSIONS: Single arterial-phase CT scanning with bolus tracking can be effectively used to detect hepatocellular carcinoma when a threshold value of 200 HU is used.

Targeting lipid metabolism in the treatment of hepatitis C virus infection.

Recently, microdomains of organelle membranes rich in sphingomyelin and cholesterol (called "lipid rafts") have been considered to act as a scaffold for the hepatitis C virus (HCV) replication complex. Using the HCV cell culture system, we investigated the effect of myriocin, a sphingomyelin synthesis inhibitor, on HCV replication. We also investigated the combined effect of myriocin with interferon (IFN) and myriocin with simvastatin. Myriocin suppressed replication of both a genotype 1b subgenomic HCV replicon (Huh7/Rep-Feo) and genotype 2a infectious HCV (JFH-1 HCV) in a dose-dependent manner (for subgenomic HCV-1b, maximum of 79% at 1000 nmol/L; for genomic HCV-2a, maximum of 40% at 1000 nmol/L). Combination treatment with myriocin and IFN or myriocin and simvastatin attenuated HCV RNA replication synergistically in Huh7/Rep-Feo cells. Our data demonstrate that the sphingomyelin synthesis inhibitor strongly suppresses replication of both the subgenomic HCV-1b replicon and the JFH-1 strain of genotype 2a infectious HCV, indicating that lipid metabolism could be a novel target for HCV therapy.

Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.

The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 +/- 16.3 vs. 36.0 +/- 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.

Highly diffusion-sensitized tensor imaging of unilateral cerebral arterial occlusive disease.

BACKGROUND AND PURPOSE: Selective neuronal death is a well-recognized histopathologic sequel to moderate ischemic brain damage. However, radiologic visualization of these changes has not been established, even with diffusion tensor imaging (DTI). We sought to determine whether DTI with b values > or =1900 s/mm(2) reveals occult diffusion abnormalities in patients with cerebral arterial occlusive disease. METHODS: Six patients (five men, one woman; mean age +/- standard deviation, 66 +/- 8 years) with unilateral internal carotid or middle cerebral arterial occlusive disease but not parenchymal T2 hyperintensity underwent 3T fast DTI with b < or = 1300 s/mm(2) and slow DTI with b > or = 1900 s/mm(2). We postprocessed mean diffusibility and fractional anisotropy (FA) images from the fast and slow DTI datasets. Standardized asymmetry indices (AIs) were used to identify regional asymmetries. Diagnostic accuracy among the DTI modalities was assessed by means of receiver operating characteristic analysis. RESULTS: In hemispheres ipsilateral to occluded vessel, AIs were significantly elevated on fast mean-diffusibility images of white matter at the levels of the internal capsule (95% confidence interval [CI]: 1.00, 1.09; P = .045) and corona radiata (95% CI: 1.01, 1.12; P = .034). AIs were significantly decreased on slow FA images at the internal capsule (95% CI: 0.84, 0.98; P = .018) and white matter at the internal capsule level (95% CI: 0.92, 1.00, P = .043). The slow FA map had the highest accuracy (89.8%) for detecting the hemisphere ipsilateral to arterial occlusion. CONCLUSION: Slow FA maps acquired by using DTI with high b values are useful for visualizing ischemic brain damage in apparently normal WM.