Expression of plasma microRNA-145-5p and its correlation with clinical features in patients with refractory epilepsy.

PURPOSE: The potential of microRNAs (miRNAs) as biomarkers has been explored in various brain diseases, including epilepsy. In this study, we are aiming to analyze the aberrant expression of miRNA-145-5p in patients with refractory epilepsy, and to further explore the correlation with clinical features. METHODS: The study cohort comprised 40 patients with refractory epilepsy and 42 healthy controls. MiRNA-145-5p expression levels in plasma were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Data analysis was performed using IBM SPSS Statistics 22.0. RESULTS: Compared with healthy controls, the expression of miRNA-145-5p in plasma was downregulated significantly in the patients with refractory epilepsy (1.180 ± 1.036 vs. 1.541 ± 0.936, p = 0.033) and mesial temporal lobe epilepsy (MTLE) (0.517 ± 0.483 vs. 1.541 ± 0.936, p = 0.004). ROC analysis showed that the area under the curve (AUC) was 0.632 (95%CI: 0.508-0.755; P = 0.040) in refractory epilepsy and 0.829 (95%CI: 0.702-0.955; P = 0.001) in MTLE. Furthermore, the expression of miRNA-145-5p was positively correlated with earlier age at epilepsy onset, more frequent seizures and past history. CONCLUSIONS: We suggested that decreased expression of miRNA-145-5p could be a potential non-invasive biomarker for early detection and clinical evaluation of refractory epilepsy. However, further studies are still required.

Statin withdrawal beyond acute phase affected outcome of thrombolytic stroke patients: an observational retrospective study.

Statin withdrawal is associated with deleterious outcome on stroke patients. Whether risk changes over time, depends on concomitant treatment of intravenous thrombolysis, or both remains to be clarified. We assessed the influence of statin withdrawal within 3 weeks while initiated in acute phase (72 hours) among patients receiving intravenous thrombolysis.This was a monocentered retrospective observational study enrolling intravenous thrombolytic stroke patients from June 2009 to May 2014. Consecutive patients were distinguished into 3 groups according to the initiation and withdrawal of statin: the reference group (not received statin in 72 hours after stroke onset); the continued group (initiated statin therapy in 72 hours and continued for at least 3 weeks); the withdrawal group (initiated statin in 72 hours and discontinued within 3 weeks). All reasons for cessation were recorded. The effects of statin withdrawal on short-, mid-, and long-term outcomes were evaluated as neurologic improvement (NIH Stroke Scale [NIHSS] score improvement ≥4 from baseline or later NIHSS = 0), death or poor outcome (modified Rankin Scale [mRS] ≥4), and favorable outcome (mRS ≤2). We further evaluate statin withdrawal effects in cardioembolic stroke patients for these outcomes.Among 443 IVT patients enrolled, 367 were included in the final study population. There were 88, 188, and 91 patients in the reference, continued, and withdrawal groups, respectively. Multivariable logistic regression showed that statin withdrawal compared with the reference was related to a lower possibility of long-term favorable outcome (OR = 0.45, 95% CI [0.22, 0.90], P = 0.024). Compared with the continued group, the adjusted OR of statin withdrawal was 0.40 (95% CI [0.22, 0.72], P = 0.002) and 2.52 (95% CI [1.34, 4.75], P = 0.004) for long-term favorable and poor/death outcomes, respectively. Also, results were similar for cardioembolic stroke patients (OR = 0.35, 95% CI [0.14, 0.89], P = 0.027 of favorable outcome and OR = 3.62, 95% CI [1.37, 9.62], P = 0.010 of poor/death outcome).In a real-world setting, for stroke patients receiving intravenous thrombolysis, statin withdrawal within 3 weeks initiating in 72 hours may have a harmful effect on the long-term neurologic outcome, even in cardioembolic stroke patients.

[Relationship between early blood pressure variability and reperfusion in acute ischemic stroke patients with intravenous thrombolysis].

OBJECTIVE: To investigate the impacts of blood pressure (BP) variability on reperfusion and long-term outcome in patients with acute ischemic stroke after intravenous thrombolysis (IVT). METHODS: The clinical data of 188 patients with acute ischemic stroke receiving IVT in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to September 2014, including hour-to-hour BP measurements, clinical manifestations, laboratory tests and radiologic findings were retrospectively analyzed. The mean 24-h BP values, and BP variability profiles, including standard deviation (sd), average squared difference between successive measurements (sv), average squared difference between rise and drop successive measurements (sv-rise and sv-drop) were calculated. Reperfusion, defined as >50% reduction in Tmax >6 s perfusion lesion volume from baseline to follow-up scans, and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months after onset were also analyzed. The favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. The binary logistic-regression model was performed to determine the independent risk factors of reperfusion and favorable outcome, respectively. RESULTS: Among 188 patients, 114 (60.6%) achieved reperfusion. During the 0-to-24 h blood pressure course, only systolic blood pressure (SBP) variability parameters were negatively correlated with reperfusion (sv: OR=0.421, 95% CI:0.187-0.950, P=0.037; sv-rise: OR=0.311, 95% CI:0.137-0.704, P=0.005) and long-term clinical outcomes (sv: OR=6.381, 95% CI:2.132-19.096, P=0.001; sv-rise: OR=5.615, 95% CI:2.152-14.654, P<0.001; sv-drop: OR=3.009, 95% CI:1.263-7.169, P=0.013). CONCLUSION: SBP variability during the first 24 hours after IVT is negatively associated with cerebral reperfusion and unfavorable neurological outcome in patients with acute ischemic stroke receiving IVT.

[Thrombus length evaluated by CT perfusion imaging and its value in prediction of recanalization after intravenous thrombolysis therapy].

OBJECTIVE: To evaluate the thrombus length on CT perfusion imaging and to assess its predictive value for recanalization and clinical outcome after intravenous thrombolysis therapy (IVT). METHODS: Fifty-six consecutive acute ischemic stroke patients with proximal middle cerebral artery (M1 segment) occlusion underwent CT perfusion imaging examination before IVT between June 2009 and May 2015. The onset-to needle time was (214.3 ± 82.0) min, and the pretreatment NIHSS score of patients was 13 (IQR 8-17). The thrombus length was determined as the distance between the proximal and distal thrombus end delineated on dynamic angiography, which was reconstructed from CT perfusion source images. Recanalization was evaluated according to Arterial Occlusive Lesion (AOL) scale, and functional outcome was based on modified Rankin scale (mRS) 3 months after IVT. Logistic regression model was used to investigate the relationship between thrombus length and recanalization, and the optimal cut-off points were determined by receiver operating characteristic curve (ROC). RESULTS: Among 56 patients, 42 (75%) achieved recanalization 24 h after IVT with mean thrombus length of (9.0 ± 4.7) mm; and 14 (25%) patients remained occlusion with mean thrombus length of (10.0 ± 5.4) mm. Logistic regression analysis demonstrated that thrombus length was an independent predictor for both recanalization (OR=0.869; 95% CI:0.764-0.987; P=0.031) and unfavorable outcome (OR=1.180;95% CI:1.023-1.362; P=0.023). Thrombus length of 11.3 mm was identified as the optimal cut-off value for recanalization (AUC=0.697, sensitivity 71.4%, specificity 76.2%), while thrombus length of 9.9 mm was the optimal cut-off value for unfavorable functional outcome (AUC=0.689, sensitivity 64.7%, specificity 71.4%). CONCLUSION: The thrombus length evaluated on CT perfusion imaging is an effective predictor for recanalization and unfavorable outcome after IVT in acute ischemic stroke patients with middle cerebral artery occlusion.

[Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy].

OBJECTIVE: To evaluate the safety of intravenous thrombolysis (IVT) in cerebral microbleeds (CMBs) patients with prior antiplatelet therapy. METHODS: Four hundred and forty nine patients with acute ischemic stroke aged (66.8 ± 12.9) years, including 298 males and 151 females, underwent susceptibility-weighted imaging (SWI) examination and MRI-guided IVT therapy between June 2009 and June 2015. The presence of CMBs, previous antiplatelet therapy, HT subtypes according to ECASS II criteria and functional outcome based on modified Rankin scale (mRS) at 3 months were analyzed in logistic regression model. RESULTS: Total 934 CMBs were detected in 172 (38.3%) patients, among whom 63 (14.0%) previously received antiplatelet therapy. All patients received intravenous recombinant tissue-plasminogen activator (rt-PA) for thrombolysis with the onset-to needle time of (229.0 ± 103.7) min. The pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 10 (IQR 5-15). Logistic regression analysis indicated that prior antiplatelet use increased neither risk of parenchymal hematoma (PH) (OR=0.809,95% CI:0.201-3.262, P=0.766) nor adverse functional outcome (OR=1.517, 95% CI:0.504-4.568, P=0.459) in patients with CMBs; while in patients with multiple CMBs (≥ 3) prior antiplatelet use increased risk of hemorrhagic transformation (OR=9.737, 95% CI: 1.364-69.494, P=0.023), but not adverse functional outcome (OR=1.697, 95% CI:0.275-10.487, P=0.569). CONCLUSION: The study indicates that in patients with CMBs, thrombolytic therapy should not be excluded due to the prior use of antiplatelet; however, the larger prospective studies are needed in future for patients with multiple CMBs.

[Older age is not related to hemorrhagic transformation and favorable outcomes in patients with wake-up ischemic stroke undergoing intravenous thrombolytic therapy].

OBJECTIVE: To investigate factors related to hemorrhagic transformation and favorable outcomes in wake-up ischemic stroke (WUIS) patients undergoing intravenous thrombolytic therapy. METHODS: Clinical data of 600 patients undergoing multimodal image-guided intravenous recombinant tissue plasminogen activator (rt-PA) therapy in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine center from May 2009 to May 2015 were retrospectively analyzed. Among 600 patients, 68 were diagnosed as WUIS including 17 cases aged 80 or older. Hemorrhagic transformation within the first 24 h after thrombolysis was assessed according to ECASS II criteria. Favorable outcome was defined as three-month modified Rankin Scale (mRS) 0-3. Univariate and binary logistic regression were used to analyze the risk factors of hemorrhagic transformation and poor clinical outcomes in WUIS patients. RESULTS: Univariate analysis showed that WUIS patients aged ≥ 80 years had a lower rate in males (41.2% vs 76.5%, P=0.007), smokers (11.8% vs 43.1%, P=0.019) and favorable outcome (52.9% vs 78.4%, P=0.043); and a higher rate of cardiac embolism (64.7% vs 35.3%, P=0.034) compared with those aged <80 years. Binary logistic regression showed that age was not an independent risk factor for favorable outcome (OR=0.524, 95% CI:0.141-1.953, P=0.336) or hemorrhagic transformation (OR=1.039, 95% CI: 0.972-1.111, P=0.262). CONCLUSION: Older age is not related to the favorable outcome or hemorrhagic transformation in WUIS patients undergoing multimodal image-guided intravenous thrombolytic therapy.

Optimal magnetic resonance perfusion thresholds identifying ischemic penumbra and infarct core: a Chinese population-based study.

AIMS: To validate whether the optimal magnetic resonance perfusion (MRP) thresholds for ischemic penumbra and infarct core, between voxel and volume-based analysis, are varied greatly among Chinese acute ischemic stroke patients. MATERIALS AND METHODS: Acute ischemic stroke patients receiving intravenous thrombolysis within 6 h of onset that obtained acute and 24-h MRP were reviewed. Patients with either no reperfusion (<30% reperfusion at 24 h) or successful reperfusion (>70% reperfusion at 24 h) were enrolled to investigate the ischemic penumbra and infarct core, respectively. The final infarct was assessed on 24-h diffusion-weighted imaging (DWI), which was retrospectively matched to the baseline perfusion-weighted imaging (PWI) images by volume or voxel-based analysis. The optimal thresholds that determined by each approach were compared. RESULTS: From June 2009 to Jan 2014, of 50 patients enrolled, 19 patients achieved no reperfusion, and 20 patients reperfused at 24 h. In patients with no reperfusion, Tmax > 6 seconds was proved of the best agreement with the final infarct in both volumetric analysis (ratio: 1.05, 95% limits of agreement:-0.23 to 2.33, P < 0.001) and voxel-by-voxel analysis (sensitivity: 72.3%, specificity: 74.3%). In patients with reperfusion, rMTT>225% (ratio:2.4, 95% limits of agreement: -6.5 to 11.4, P < 0.001) was found of the best volumetric agreement with the final infarct, while Tmax > 5.6 seconds (sensitivity: 76.8%, specificity: 70.3%) performed most accurately in voxel-based analysis. CONCLUSION: Among Chinese acute stroke patients, volume of Tmax >6 seconds may precisely target ischemic penumbra tissue as good as voxel-based analysis performed, albeit no concordant MRP parameter is found to accurately predict infarct core because reperfusion occurred within 24 h after thrombolysis fails to restrain the infarct growth.

[Impact of cerebral microbleeds on outcomes of acute ischemic stroke treated with intravenous thrombolysis].

OBJECTIVE: To assess the impact of cerebral microbleeds (CMBs) on clinical outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis. METHODS: The clinical data of 225 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 were reviewed. The severity of CMBs and hemorrhagic transformation (HT) after thrombolytic therapy and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months were evaluated. Favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. Multivariate logistic-regression analysis and binary logistic-regression were used to determine independent risk factors of HT and favorable outcome. RESULTS: The mean age of 225 patients was (66.29±13.01) y, 73 (32.4%) patients were women, mean pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 11.40±5.89, and onset-to-needle time was (238.40±89.16) min. Totally, 522 CMBs were detected in 91 patients (36.1%). Postlytic radiological HT was found in 64 patients (28.4%), among which 43 (19.1%) were hemorrhagic infarction and 21 (9.3%) were parenchymal hematoma. Univariate analysis showed that patients with HT had higher NIHSS score and more incidence of atrial fibrillation and that patients with unfavorable outcome were older and had higher NIHSS score and more CMBs. Multivariate logistic regression analysis showed that multiple CMBs (>=3) was independently associated with parenchymal hematoma (OR=4.957, 95%CI 1.306-18.811, P=0.019), but not with hemorrhagic infarction (OR=1.204, 95%CI 0.386-3.754, P=0.749). Binary logistic regression analysis showed that multiple CMBs (>=3) was independently associated with unfavorable outcome (OR=3.496, 95%CI 1.381-8.849, P=0.008). CONCLUSION: Multiple CMBs are correlated with parenchymal hematoma and unfavorable neurological outcome after thrombolytic therapy in patients with acute ischemic stroke.

[Impact of atrial fibrillation on clinical outcome in patients with acute ischemic stroke undergoing thrombolytic therapy].

OBJECTIVE: To investigate the impact of atrial fibrillation (AF) on clinical outcomes in patients with acute ischemic stroke undergoing thrombolytic therapy. METHODS: The clinical data of 330 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine between June 2009 and August 2013 were reviewed. Clinical outcomes in AF and non-AF groups were evaluated by univariate and multivariate analysis. Favorable outcome was defined as a modified Rankin Scale (mRS) 0-2 on day 90. Hemorrhagic transformation (HT) was classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH) within the first 24h according to ECASS II criteria. Hypoperfusion and severe hypoperfusion were defined as Tmax >6 s and >8 s, respectively. The rate of reperfusion was compared between AF and non-AF groups. RESULTS: Among 330 patients, 137(41.5%) had AF. Compared with non-AF patients, patients with AF were older [(71.7±11.5)y vs (63.4±13.2)y, P<0.001], had higher baseline National Institutes of Health Stroke Scale [IQR, 13(8-16) vs 9(5-15), P<0.001], higher rate of HT(HI: 28.5% vs 17.1%, P=0.015; PH: 13.9% vs 4.1%, P=0.002), and lower rate of favorable outcome (41.5% vs 58.0%, P=0.005) at d 90. After adjustment, AF was not a risk factor for favorable outcome (OR=0.920, 95%CI:0.533-1.586; P=0.763) and mortality (OR=1.381, 95%CI:1.096-1.242; P=0.466) on day 90. AF was also not associated with HI (OR=1.676, 95%CI: 0.972-3.031; P=0.088), but it increased the rate of PH (OR=3.621, 95%CI: 1.403-9.344; P=0.008). Among 94 patients with pre- and post-thrombolytic perfusion-weighted image, AF was not associated with increased rate of reperfusion for hypoperfusion (Tmax >6 s, OR=1.12, 95%CI: 0.35-3.63, P=0.849), but was correlated with increased rate of reperfusion for severe hypoperfusion (Tmax>8 s, OR=10.57, 95%CI:1.16-96.50, P=0.037). CONCLUSION: The presence of AF has no independent impact on neurological outcome in thrombolytic patients with acute ischemic stroke. It is associated with increased reperfusion rate of more severe hypoperfusion area and higher frequency of PH.

Evaluation of brain iron content based on magnetic resonance imaging (MRI): comparison among phase value, R2* and magnitude signal intensity.

BACKGROUND AND PURPOSE: Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn't commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron. METHODS: We measured both phase values and R2* in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2* and brain iron. RESULTS: We found phase value correlated with R2* in substantia nigra (r = -0.723, p<0.001) and putamen (r = -0.514, p = 0.010), while no correlations in red nucleus (r = -0.236, p = 0.268) and globus pallidus (r = -0.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = -0.593, p = 0.002), substantia nigra (r = -0.521, p = 0.009), globus pallidus (r = -0.750, p<0.001) and putamen (r = -0.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = -0.982, P<0.001). CONCLUSIONS: Our study indicates that phase value may not be used for assessing the iron content in some brain regions especially globus pallidus. The new magnitude method is highly consistent with R2* especially in globus pallidus, and we assume that this approach may be acceptable as an index of iron content in iron-rich brain regions.