The JMJD6/HURP axis promotes cell migration via NF-κB-dependent centrosome repositioning and Cdc42-mediated Golgi repositioning.

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA-associated acetyl-tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6-guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6-induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF-κB-induced CR and subsequently CR-dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF-κB-CR-Cdc42 cascade collectively dictate GR.

Phase I study of expanded natural killer cells in combination with cetuximab for recurrent/metastatic nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) cells express high levels of epidermal growth factor receptor (EGFR). Cetuximab is an anti-EGFR monoclonal antibody that promotes natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) via engagement of CD16. We studied safety and efficacy of combining cetuximab with autologous expanded NK cells in patients with recurrent and/or metastatic NPC who had failed at least two prior lines of chemotherapy. METHODS: Seven subjects (six patients) received cetuximab every 3 weeks (six doses maximum) in the pre-trial phase. Autologous NK cells, expanded by co-culture with irradiated K562-mb15-41BBL cells, were then infused on the day after administration of cetuximab. Primary and secondary objectives were to determine safety of this combination therapy and to assess tumor responses, respectively. RESULTS: Median NK cell expansion from peripheral blood mononucleated cells after 10 days of culture with K562-mb15-41BBL was 274-fold (range, 36-534, n = 10), and the median expression of CD16 was 98.4% (range, 67.8-99.7%). Skin rash, the commonest side effect of cetuximab in the pre-trial phase, was not exacerbated by NK cell infusion. No intolerable side effects were observed. Stable disease was observed in four subjects and progressive disease in three subjects. Three patients who received NK cells twice had time to disease progression of 12, 13, and 19 months. CONCLUSION: NK cells with high ADCC potential can be expanded from patients with heavily pre-treated NPC. The safety profile and encouraging clinical responses observed after combining these cells with cetuximab warrant further studies of this approach. (clinicalTrials.gov NCT02507154, 23/07/2015). PRECIS: Engaging NK cell-mediated ADCC using cetuximab plus autologous NK cells in EGFR-positive NPC was well tolerated among heavily pre-treated recurrent NPC. Promising results were observed with 3 out of 7 subjects demonstrating durable stable disease.

Coronal CT is Comparable to MR Imaging in Aiding Diagnosis of Dementia in a Memory Clinic in Singapore.

PURPOSE: The present study investigated (a) the agreement between computerized tomography (CT) and 3 T magnetic resonance imaging (MRI) in the visual grading of medial temporal atrophy (MTA); and (b) whether MTA on CT differentiated patients with dementia from no dementia in memory clinics. MATERIALS AND METHODS: Data were obtained from patients who underwent CT scans at the National University Hospital of Singapore, and from a subsample who subsequently underwent 3 T MRI scans in a research study. Agreements and disagreements between CT and MRI were determined. Area under the curve (AUC) analyses determined if CT-graded MTA distinguished patients with dementia from no dementia. RESULTS: Of the 107 patients in the subsample, MTA scores of 71 agreed on both CT and MRI. The true positive rate between CT and MRI for MTA scores ≥2 was 79.7%. The true negative rate for MTA scores between 0 and 1 was 96.4%. CT underestimated MTA severity in 33 of 36 disagreements with the MRI. MTA scores ≥2 on CT distinguished dementia from no dementia in both discovery [n=263; AUC (95% confidence interval)=0.77 (0.72-0.83); sensitivity=0.69; specificity=0.74] and validation [n=264; AUC (95% confidence interval)=0.77 (0.71-0.82); sensitivity=0.72; specificity=0.72] groups. CONCLUSIONS: MTA graded on CT is a viable alternative to MRI to aid in the diagnosis of dementia in memory clinics.

The "Blush" Sign on Computed Tomography Angiography is an Independent Predictor of Hematoma Progression in Primary Hypertensive Hemorrhage.

BACKGROUND AND PURPOSE: Hypertension is an important etiology of intracerebral hemorrhage (ICH) in neurosurgical practice. Contrast extravasation on computed tomography angiography, known as the "spot sign", has been described as an independent predictor of hematoma progression and clinical deterioration. However, its role in hypertensive ICH alone has not been determined and is the primary aim of this study. MATERIALS AND METHODS: A retrospective review was carried out of patients with hypertensive ICH admitted to our institution between May 2014 and December 2016. Evaluation of the neuroimaging studies of these patients revealed two distinct morphologies, "spot" and "blush" sign. These distinct signs and covariates were tested for association with hematoma expansion and mortality using multivariate logistic regression. The accuracy of the "spot" and "blush" signs as predictors of hematoma expansion and mortality was determined using receiver-operator characteristic (ROC) analysis. RESULTS: A total of 54 patients were identified as hypertensive ICH during the study period. "spot" sign was observed in 11 (20.4%) of the study population. Contrast extravasation (blush-sign) was seen in 7 (14.8%) patients. The "blush" was an independent predictor of hematoma expansion (odds ratio [OR] 6.052; confidence interval [CI] 1.036-15.945 [P = .012]) and mortality (OR 3.305; CI 1.240-25.414 [P = .032]). With ROC analysis, the "blush" sign was found to have a better predictive value for significant hematoma expansion (area under the curve [AUC]: .795) than the spot sign (AUC: .432). CONCLUSION: The "blush" sign has better accuracy for predicting hematoma expansion in hypertensive ICH and could be used to risk stratify these patients for early therapeutic interventions.

Nongated Cardiac Computed Tomographic Angiograms for Detection of Embolic Sources in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We assessed the feasibility of obtaining diagnostic quality images of the heart and thoracic aorta by extending the z axis coverage of a non-ECG-gated computed tomographic angiogram performed in the primary evaluation of acute stroke without increasing the contrast dose. METHODS: Twenty consecutive patients with acute ischemic stroke within the 4.5 hours of symptom onset were prospectively recruited. We increased the longitudinal coverage to the domes of the diaphragm to include the heart. Contrast administration (Omnipaque 350) remained unchanged (injected at 3-4 mL/s; total 60-80 mL, triggered by bolus tracking). Images of the heart and aorta, reconstructed at 5 mm slice thickness in 3 orthogonal planes, were read by a radiologist and cardiologist, findings conveyed to the treating neurologist, and correlated with the transthoracic or transesophageal echocardiogram performed within the next 24 hours. RESULTS: Of 20 patients studied, 3 (15%) had abnormal findings: a left ventricular thrombus, a Stanford type A aortic dissection, and a thrombus of the left atrial appendage. Both thrombi were confirmed by transesophageal echocardiography, and anticoagulation was started urgently the following day. None of the patients developed contrast-induced nephropathy on follow-up. The radiation dose was slightly increased from a mean of 4.26 mSV (range, 3.88-4.70 mSV) to 5.17 (range, 3.95 to 6.25 mSV). CONCLUSIONS: Including the heart and ascending aorta in a routine non-ECG-gated computed tomographic angiogram enhances an existing imaging modality, with no increased incidence of contrast-induced nephropathy and minimal increase in radiation dose. This may help in the detection of high-risk cardiac and aortic sources of embolism in acute stroke patients.

Intracranial hemorrhage in a patient with sub-massive pulmonary embolism treated with EkoSonic endovascular system directed thrombolysis.

Ultrasound-assisted catheter-directed thrombolysis therapy has emerged more recently as a management strategy for patients with intermediate risk pulmonary embolism and has shown promising results in clinical trials by early reversal of right ventricle dilation, reduced pulmonary hypertension, and decreased anatomic thrombus burden. This therapeutic strategy requires a small fraction of the systemic fibrinolytic dose and is therefore associated with a reduced bleeding risk. Although intracranial hemorrhage has not been reported in clinical trials, it is a possible complication. Here we report the first case of intracranial hemorrhage related to the use of EkoSonic™ Endovascular System directed thrombolysis in a patient with large bilateral pulmonary embolism without any identifiable bleeding risks. © 2017 Wiley Periodicals, Inc.

Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first?

A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.

Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value. METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more. RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001). CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.

Good Intracranial Collaterals Trump Poor ASPECTS (Alberta Stroke Program Early CT Score) for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, large early infarct size estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated with poorer outcomes and is a relative contraindication for recanalization therapies. The state of the intracranial collateral circulation influences the functional outcome and may be a variable to consider before thrombolysis. We evaluated the prognostic effect of the collateral circulation in patients with thrombolyzed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS. MATERIALS AND METHODS: Patients with anterior circulation acute ischemic stroke who received a computed tomographic angiogram and subsequent treatment with intravenous tissue-type plasminogen activator from 2010 to 2013 were studied. Two independent neuroradiologists determined their ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤7 points) and small volume infarcts (ASPECTS 8-10). In addition, we evaluated a third group with very large volume infarcts (ASPECTS≤5 points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2 at 3 months. RESULTS: A total of 300 patients were included in the final analysis. For patients with very large volume infarcts (ASPECTS≤5 points), univariable analysis showed that younger age, male sex, lower National Institute of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence interval, 0.89-0.97; P=0.002) and good collaterals by ASPECTS-collaterals system (odds ratio, 1.34; 95% confidence interval, 1.15-1.57; P<0.001) were associated with good outcomes. CONCLUSIONS: In patients with large and very large volume infarcts, good collaterals as measured by the ASPECTS-collaterals system is associated with improved outcomes and can help select patients for intravenous thrombolysis.

Intravenous Thrombolysis for Acute Ischemic Stroke due to Cervical Internal Carotid Artery Occlusion.

BACKGROUND: Internal carotid artery (ICA) occlusions are poorly responsive to intravenous thrombolysis with tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS). Most study populations have combined intracranial and extracranial ICA occlusions for analysis; few have studied purely cervical ICA occlusions. We evaluated AIS patients with acute cervical ICA occlusion treated with IV-tPA to identify predictors of outcomes. METHODS: We studied 550 consecutive patients with AIS who received IV-tPA and identified 100 with pure acute cervical ICA occlusion. We evaluated the associations of vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, and leptomeningeal collateral vessel status via 3 different grading systems, with functional recovery at 90 days, mortality, recanalization of the primary occlusion, and symptomatic intracranial hemorrhage (SICH). Modified Rankin Scale score 0-1 was defined as an excellent outcome. RESULTS: The 100 patients had mean age of 67.8 (range 32-96) and median NIHSS score of 19 (range 4-33). Excellent outcomes were observed in 27% of the patients, SICH in 8%, and mortality in 21%. Up to 54% of the patients achieved recanalization at 24 hours. On ordinal regression, good collaterals showed a significant shift in favorable outcomes by Maas, Tan, or ASPECTS collateral grading systems. On multivariate analysis, good collaterals also showed reduced mortality (OR .721, 95% CI .588-.888, P = .002) and a trend to less SICH (OR .81, 95% CI .65-1.007, P = .058). Interestingly, faster treatment was also associated with favorable functional recovery (OR 1.028 per minute, 95% CI 1.010-1.047, P = .001). CONCLUSIONS: Improved outcomes are seen in patients with early acute cervical ICA occlusion and better collateral circulation. This could be a valuable biomarker for decision making.

Intracranial stenosis, cerebrovascular diseases, and cognitive impairment in chinese.

Extracranial carotid artery disease has been shown to be related to cognitive deficits. However, limited data are available on intracranial stenosis (ICS) and cognitive impairment. We investigate the association between ICS and cognitive impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of Dementia in Singapore Study, underwent comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI), including 3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment no dementia and dementia were diagnosed according to internationally accepted diagnostic criteria. Linear and logistic regression models were adjusted for age, sex, education, vascular risk factors, and other MRI markers. A total of 29 (10.4%) persons had ICS on MRA, which was significantly associated with both composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of ICS: -0.37 (95% confidence interval: -0.63, -0.12)] and specific domains including executive function, language, visuomotor speed, verbal memory, and visual memory. ICS was also related to significant cognitive impairment (odds ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the presence of lacunar infarcts, the associations of ICS with both composite and domain-specific Z-scores, and significant cognitive impairment became nonsignificant; however, adjustment for other MRI markers did not alter these associations. In this Chinese population, presence of ICS was associated with cognitive impairment independent of vascular risk factors. These associations may be mediated through the presence of infarcts.

External validation of the Boston Acute Stroke Imaging Scale and M1-BASIS in thrombolyzed patients.

BACKGROUND AND PURPOSE: Radiological findings play an essential role in therapeutic decision making and prognostication in acute ischemic stroke (AIS). The Boston Acute Stroke Imaging Scale (BASIS) and Middle Cerebral Artery-BASIS (M1-BASIS) methodologies are rapid purely radiological instruments and easily applicable for patients with AIS. We validated these methods in patients with AIS treated with intravenous tissue-type plasminogen activator. METHODS: For BASIS, patients were labeled as having major stroke if there was occlusion of distal internal carotid artery, proximal (both M1 and M2 segments) of middle cerebral artery or the basilar artery, or an Alberta Stroke Program Early CT Score≤7. M1-BASIS differs from BASIS by classifying AIS patients with M2 occlusion as a minor stroke. We evaluated these classification systems for predicting functional outcomes (modified Rankin Scale score 0-1) at 3 months. RESULTS: Two hundred sixty-five consecutive AIS patients treated with intravenous tissue-type plasminogen activator were included. On multivariate analysis, younger age (odds ratio, 1.039, 95% confidence interval, 1.009-1.070; P=0.011), lower National Institutes of Health Stroke Scale score (odds ratio, 1.140; 95% confidence interval, 1.073-1.210; P<0.001), and minor stroke by M1-BASIS (odds ratio, 2.376; 95% confidence interval, 1.047-5.393; P=0.039) were independent predictors of good functional outcome. When compared with National Institutes of Health Stroke Scale, the receiver operating characteristic curves for both BASIS (area under the curve, 0.721) and M1-BASIS (area under the curve, 0.795) correlated well with clinical severity scores. M1-BASIS has an additive effect with the National Institutes of Health Stroke Scale score to predict good outcomes. CONCLUSIONS: The purely radiological M1-BASIS correlates well with the clinical severity of stroke and can be a reliable prognostication tool in thrombolyzed AIS patients. This system might find an important place in the current era of telestroke.

Computer tomography for prediction of cognitive outcomes after ischemic cerebrovascular events.

BACKGROUND: The aim of this study was to evaluate whether parameters noted on a single, acute computed tomographic (CT) scan, are associated with significant cognitive impairment (SCogI), and can help in the prediction of SCogI 3-6 months after stroke or transient ischemic attack (TIA). METHODS: Patients with a recent (≤14 days) ischemic stroke or TIA, without preexisting dementia, underwent noncontrast CT scan within 24 hours of admission. A formal neuropsychologic battery was administered 3-6 months from index stroke. SCogI was defined as moderate cognitively impaired, not demented (CIND) (≥3 domains impaired), and dementia diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Logistic regression models were used to examine associations between CT parameters and SCogI. Receiver operating characteristic analysis with an area under the curve (AUC) was performed to assess discriminatory ability of radiological parameters for SCogI. RESULTS: In all, 318 patients were included: 250 (78.6 %) with ischemic stroke and 68 (21.4%) with TIA; the mean age was 59.8 (±11.4) years. At 3-6 months, 76 (23.9 %) had SCogI (67 CIND moderate and 9 dementia). The presence of significant atrophy (P = .02) and chronic infarcts (P = .03) were associated with SCogI at 3-6 months. A significant increase in AUC was noted after addition of summarized CT results to a clinical score derived from age and baseline Montreal Cognitive Assessment (cutoff 21 of 22) for detection of SCogI: .83 (.78-.89) to .86 (.82-.91); P = .03. CONCLUSIONS: CT parameters are independently associated with SCogI at 3-6 months after an ischemic cerebrovascular event and may be a clinically useful component in predicting for SCogI after stroke.

Prevalence of cognitive impairment in Chinese: epidemiology of dementia in Singapore study.

OBJECTIVE: To study the prevalence of and associated factors for cognitive impairment and dementia in community dwelling Chinese from Singapore. METHODS: This study includes Chinese subjects from the Epidemiology of Dementia in Singapore (EDIS) study, aged ≥60 years, who underwent comprehensive examinations, including cognitive screening with the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen positive participants subsequently underwent extensive neuropsychological testing and cerebral MRI. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to internationally accepted criteria. The prevalence of cognitive impairment and dementia were computed per 5 year age categories and gender. To examine the relationship between baseline associated factors and cognitive impairment, we used logistic regression models to compute odd ratios with 95% CI. RESULTS: 1538 Chinese subjects, aged ≥60 years, underwent cognitive screening: 171 (15.2%) were diagnosed with any cognitive impairment, of whom 84 were CIND mild, 80 CIND moderate and seven had dementia. The overall age adjusted prevalence of CIND mild was 7.2%; CIND moderate/dementia was 7.9%. The prevalence increased with age, from 5.9% in those aged 60-64 years to 31.3% in those aged 75-79 years and 44.1% in those aged ≥80 years. Multivariate analysis revealed age, diabetes and hyperlipidaemia to be independently associated with cognitive impairment. CONCLUSIONS: In present study, the overall prevalence of cognitive impairment and dementia in Chinese was 15.2%, which is in the same range as the prevalence reported in Caucasian and other Asian populations.

Comparison of methodologies in volumetric orbitometry.

PURPOSE: The rate at which the orbit matures is not well-documented. Limiting this pursuit are the difficulties inherent in measuring orbital volumes accurately. This study compared 3 common methods of determining orbital volume and sought to identify an accurate, practical manner for doing so. METHODS: The volume of 1 orbit of 8 human cadaver heads was independently measured using 3 different methods: 1) CT was performed, and images were analyzed with 3-dimensional (3D) volumetric software; 2) The same orbits were then exenterated and a silicone cast was taken. The cast volumes were measured by water displacement; 3) The orbits were then filled with 1-mm glass beads that were transferred to a graduated cylinder where their volume was determined. The data were analyzed statistically. RESULTS: Intraobserver agreements were good for both beads and casts. Interobserver agreements were good for both beads and CT (p > 0.05). Values obtained using the bead method were equal to values obtained using the cast method (p > 0.05). However, agreement between direct (orbital fillers and casts) and indirect measurements (radiographic techniques) was not satisfactory (p < 0.05). CONCLUSIONS: Independent of method, determining orbital volume is inherently difficult owing to the hyperbolic parabola that is the orbit entrance; all methods require estimation. Glass beads and casts yielded more reproducible values but can only be used in cadavers. CT measurement is prone to error due to the variability of methodologies used but allows access to enormous testing populations. Interstudy comparison is currently not possible. CT volumetric software with strict universal standards for estimating the anterior limit of the orbit appears to be the best method of studying human orbital volumes.

Early and continuous neurologic improvements after intravenous thrombolysis are strong predictors of favorable long-term outcomes in acute ischemic stroke.

BACKGROUND: Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate changes in their neurologic status within the first 24 hours of intravenous thrombolysis with IV tPA. However, there are little available data on the course of clinical recovery in subacute 2- to 24-hour window and its impact. We evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can predict functional outcomes in AIS patients at 3 months. METHODS: Data for consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset during 2007-2011 were prospectively entered in our thrombolyzed registry. National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was defined as a reduction in NIHSS score by 10 or more points from baseline or an absolute score of 4 or less points at 2 hours. Continuous neurologic improvement (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and 24 hours or an absolute score of 4 or less points at 24 hours. Favorable functional outcomes at 3 months were determined by modified Rankin Scale (mRS) score of 0-1. RESULTS: Of 2460 AIS patients admitted during the study period, 263 (10.7%) received IV tPA within the time window; median age was 64 years (range 19-92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130 (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The female gender, age, and baseline NIHSS score were found to be significantly associated with CNI on univariate analysis. On multivariate analysis, NIHSS score at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]: 1.140-4.285; P=.024) were found to be independent predictors of CNI. Factors associated with favorable outcomes at 3 months on univariate analysis were younger age, female gender, hypertension, NIHSS score at onset, recanalization on transcranial Doppler (TCD) monitoring or repeat computed tomography (CT) angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at onset (OR per 1-point increase: .835, 95% CI: .751-.929, P<.001), 2-hour TCD recanalization (OR: 3.048, 95% CI: 1.537-6.046; P=.001), 24-hour CT angiographic recanalization (OR: 4.329, 95% CI: 2.382-9.974; P=.001), ENI at 2 hours (OR: 2.536, 95% CI: 1.321-5.102; P=.004), and CNI (OR: 7.253, 95% CI: 3.682-15.115; P<.001) were independent predictors of favorable outcomes at 3 months. CONCLUSIONS: Women are twice as likely to have CNI from the 2- to 24-hour period after IV tPA. ENI and CNI within the first 24 hours are strong predictors of favorable functional outcomes in thrombolyzed AIS patients.

Multi-stage segmentation of white matter hyperintensity, cortical and lacunar infarcts.

Cerebral abnormalities such as white matter hyperintensity (WMH), cortical infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently present in patients with stroke and dementia. Up to date, there are limited algorithms available to automatically delineate these cerebral abnormalities partially due to their complex appearance in MR images. In this paper, we describe an automated multi-stage segmentation approach for labeling the WMH, CI, and LI using multi-modal MR images. We first automatically segment brain tissues (white matter, gray matter, and CSF) based on the T1-weighted image and then identify hyperintense voxels based on the fluid attenuated inversion recovery (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2-weighted, and FLAIR images. The segmentation accuracy is evaluated using a community-based sample of 272 old adults. Our results show that the automated segmentation of the WMH, CI, and LI is comparable with manual labeling in terms of spatial location, volume, and the number of lacunes. Additionally, the WMH volume is highly correlated with the visual grading score based on the Age-Related White Matter Changes (ARWMC) protocol. The evaluations against the manual labeling and ARWMC visual grading suggest that our algorithm provides reasonable segmentation accuracy for the WMH, CI, and LI.

Magnetic Resonance Imaging Study of the Pericranial Flap and Its Local Effects Following Endoscopic Craniofacial Resection.

OBJECTIVES/HYPOTHESIS: To describe the magnetic resonance imaging (MRI) characteristics of the pericranial flap, changes in the pericranial flap thickness over time, presence of frontal sinus opacification, and presence of frontal lobe herniation into the nasal cavity. STUDY DESIGN: Retrospective case series. METHODS: Seventeen consecutive endoscopic craniofacial resections with pericranial flap reconstruction performed at a tertiary hospital from 2010 to 2019 were reviewed. Sixty-eight serial MRI scans were evaluated. RESULTS: All pericranial flaps consistently featured a homogenous appearance on T1-weighted sequence and enhanced with contrast. On T2-weighted sequence, the skull base reconstruction demonstrated four layers of alternating hypo- and hyperintensity, which corresponded with the inlay synthetic graft or neodura (hypointense), loose areolar tissue (hyperintense), fibrous pericranium (hypointense), and nasal mucosa or granulation tissue (hyperintense). The mean pericranial flap thickness was 9.9 mm. In thicker flaps, the loose areolar layer contributed the bulk of the thickness. Of 13 patients who underwent three or more serial MRI scans, 11 flaps (84.6%) were stable and two (15.4%) had >50% reduction in their original thickness over time. Thirteen of 17 (76.5%) patients had frontal sinus opacification on follow-up. None developed frontal sinus mucoceles or frontal lobe herniation. CONCLUSIONS: The pericranial flap has a distinctive MRI appearance, especially on T2-weighted sequence. The thickness of the flap remains relatively stable over time for most patients even following radiotherapy. It is a sturdy flap that is able to support the frontal lobe. Frontal sinus obstruction is common, although complications from this appear to be rare. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E90-E97, 2021.

Imaging findings on contrast-enhanced ultrasound, magnetic resonance imaging and hybrid positron emission tomography in Takayasu arteritis: a case report.

This case report demonstrates the potential of contrast-enhanced ultrasound (CEUS) in diagnosing active arterial wall inflammation in a symptomatic patient with Takayasu arteritis (TA). To our knowledge, this is the first case which demonstrates pictorial correlation of arterial wall neovascularity on CEUS with mural edema on magnetic resonance imaging and metabolic activity on positron emission tomography - computed tomography in the same patient. As TA is a chronic disease which requires long-term follow-up, CEUS could be the potential imaging modality of choice as it is radiation-free, non-nephrotoxic and easily available.

Temporal Evolution of Intramural Esophageal Dissection with 3D Reconstruction and Cinematic Virtual Fly-Through.

Intramural esophageal dissection is an uncommon condition, involving the separation of the esophageal mucosa from the muscular layers. To our knowledge, the temporal evolution of intramural esophageal dissection on computed tomography has not been previously demonstrated. We present a case of a 51-year-old male who first presented to the emergency department with fever, odynophagia, and dysphagia. He was treated for acute tonsillitis and discharged, but presented again after 10 days with worsening symptoms. A series of radiographs and computed tomography studies, with 3D reconstruction and cinematic virtual fly-through, in these 2 admissions depicts the temporal evolution of intramural hematoma to subsequent intramural esophageal dissection. Recognizing its appearance on imaging is invaluable in distinguishing it from other important differential diagnoses. A complete description of the case, relevant radiologic imaging, and review of the relevant literature are provided.