Effect of different thresholds for CT perfusion volumetric analysis on estimated ischemic core and penumbral volumes.

PURPOSE: This single-center study compared three threshold settings for automated analysis of the ischemic core (IC) and penumbral volumes using computed tomographic perfusion, and their accuracy for predicting final infarct volume (FIV) in patients with anterior circulation acute ischemic stroke (AIS). METHODS: Fifty-two consecutive AIS patients undergoing mechanical thrombectomy (November 2015-March 2018) were included. Perfusion images were retrospectively analyzed using a single CT Neuro perfusion application (syngo.via 4.1, Siemens Healthcare GmbH). Three threshold values (S1-S3) were derived from another commercial package (RAPID; iSchema View) (S1), up-to-date syngo.via default values (S2), and adapted values for syngo.via from a reference study (S3). The results were compared with FIV determined by non-contrast CT. RESULTS: The median IC volume (mL) was 24.6 (interquartile range: 13.7-58.1) with S1 and 30.1 (20.1-53.1) with S2/S3. After removing the contralateral hemisphere from the analysis, the median IC volume decreased by 1.33(0-3.14) with S1 versus 9.13 (6.24-14.82) with S2/S3. The median penumbral volume (mL) was 74.52 (49.64-131.91), 77.86 (46.56-99.23), and 173.23 (125.86-200.64) for S1, S2, and S3, respectively. Limiting analysis to the affected hemisphere, the penumbral volume decreased by 1.6 (0.13-9.02), 19.29 (12.59-26.52), and 58.33 mL (45.53-74.84) for S1, S2, and S3, respectively. The correlation between IC and FIV was highest in patients with successful recanalization (n = 34, r = 0.784 for S1; r = 0.797 for S2/S3). CONCLUSION: Optimizing thresholds significantly improves the accuracy of estimated IC and penumbral volumes. Current recommended values produce diversified results. International guidelines based on larger multicenter studies should be established to support the standardization of volumetric analysis in clinical decision-making.

Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events.

BACKGROUND/AIM: We aimed to analyze the diagnostic value of total tau (T-tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. PATIENTS AND METHODS: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8±50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. RESULTS: T-tau was higher in patients with stroke [1.0 pg/ml (IQR=0.3-2.2)] than with TIA [0.5 pg/ml (IQR=0.2-1.0), p=0.02]. The levels of S100B were also increased in stroke [0.082 µg/l (IQR=0.049-0.157)] patients compared to TIA patients [0.045 µg/l (IQR=0.03-0.073), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 µg/l (IQR=9.30-16.14)] compared to those with TIA [10.96 µg/l (IQR=7.98-15.33), p=0.30] were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). CONCLUSION: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months.

Serum High-Sensitive C-reactive Protein May Reflect Periodontitis in Patients With Stroke.

BACKGROUND/AIM: Chronic infectious diseases are believed to increase the risk of stroke. We aimed to evaluate the prevalence of periodontal disease and its association with systemic inflammatory processes in patients suffering an acute stroke/transient ischemic attack (TIA). PATIENTS AND METHODS: Altogether 36 acute stroke/TIA patients underwent clinical, laboratory and radiological examinations. The level of systemic inflammation was analyzed both with routine measurements of plasma C-reactive protein (p-CRP) and serum high-sensitivity CRP (s-hsCRP) to analyze their associations with periodontitis. The diagnostic criteria for periodontitis included increased probing depth (>4 mm) measured from four different sites, bleeding on probing, and horizontal (>1 mm), vertical (>1 mm) or apical bone loss observed on orthopantomography. RESULTS: Twenty-six (72.2%) patients were diagnosed with periodontitis. Only five of the patients with periodontitis (19.2%) had elevated p-CRP values whereas the majority, (17/26; 65.4%) had elevated s-hsCRP values (p<0.01). Absolute s-hsCRP values in patients with periodontitis (8.9±12.5 mg/l) were significantly higher than in patients without periodontitis (2.3±3.0 mg/l; p<0.05). Absolute p-CRP concentrations did not differ (2.3±5.8 vs. 2.4±5.1 mg/l; p=not significant). The total number of periodontitis findings was significantly associated with s-hsCRP values (r=1.83) but not with p-CRP values. Conversely, seventeen of the nineteen patients with elevated s-hsCRP (89.5%) indicative of systemic inflammation had periodontitis. CONCLUSION: Periodontitis is a common finding among patients with acute stroke/TIA as over 80% of patients with cryptogenic stroke/TIA had periodontitis. S-hsCRP is a useful tool for detecting subclinical systemic inflammation.

Serum Neurofilament Light Chain Concentration Correlates with Infarct Volume but Not Prognosis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We studied serum neurofilaments diagnostic value in patients with acute ischemic stroke (AIS) or TIA and evaluated any correlation with symptom severity, cerebral infarction volume, aetiology, and clinical outcome. METHODS: One hundred and thirty-six patients (101 with AIS, and 35 with TIA) were included. Acute-phase serum neurofilament light chain (sNfL) was analyzed with a novel ultrasensitive single molecule array (Simoa). Cerebral infarction volume was measured from brain computed tomography in the subacute phase (>2 days). Stroke aetiology was defined by trial of ORG 10172 in acute stroke treatment classification, severity by National Institute of Health stroke scale (NIHSS) and the degree of disability by the Modified Rankin Scale (mRS) after 90 days. RESULTS: sNfL was markedly higher in patients with AIS (89.5 pg/mL [IQR: 44.7-195.3]) than with TIA (25.2 pg/mL [IQR: 14.6-48.0]), P= <.001), also after adjusting for age, NIHSS, and stroke volume (P= .003). In receiver operating characteristic analysis, sNfL concentration greater than or equal to 49 pg/mL proved to be the best cut-off value to differentiate between patients with stroke and those with TIA (sensitivity of 73% and specificity of 80%). sNfL concentration significantly correlated with cerebral infarction volume (r = .413, P= <.001), this association remained significant after adjusting for established predictors (P= .019). Patients with AIS due to cardioembolism or large artery atherosclerosis had the highest sNfL concentrations. NIHSS on admission (r = .343, P = <.001) and mRS scores after 3 months (r = .306, P = .004) correlated with sNfL concentration, however functional outcome 3 months after stroke was not associated with sNfL after adjusting for potential confounders. CONCLUSIONS: Cases with stroke were distinguishable from those with TIA following the determination of sNfL in the blood samples. The presence and amount of axonal damage estimated by sNfL correlated with the final cerebral infarction volume but was not predictive of degree of disability.

Mechanical Thrombectomy of Large Artery Occlusion Is Beneficial in Octogenarians.

AIM: Recent trials have established the benefit of endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large artery occlusion (LAO). However, older patients were often excluded from trials. EVT outcomes were retrospectively compared between octogenarians and younger patients treated for LAO in a tertiary hospital. PATIENTS AND METHODS: A total of 199 consecutive patients with anterior circulation AIS that underwent EVT between 2009 and 2015 in the Kuopio University Hospital were included. Patients were dichotomized into younger (<80 years, N=162) and older (≥80 years, N=37) groups. Baseline, imaging, and procedural characteristics, the 3-month modified Rankin Scale (mRS), and 1-year mortality were assessed. To conduct a number-needed-to-treat (NNT) analysis, data on age-dichotomized control groups from a meta-analysis were acquired. RESULTS: Compared to younger patients, older patients exhibited atrial fibrillation (57% vs. 21%, p<0.01) and coronary artery disease (49% vs. 20%, p<0.01) more frequently and Internal Carotid Artery (ICA) occlusion less frequently (22% vs. 55%, p<0.01). Similar proportions of patients received preprocedural intravenous recombinant tissue-type plasminogen activator (r-tPA; 57% vs. 67%), general anesthesia (35% vs. 41%), and reperfusion (Thrombolysis in Cerebral Infarction scale 2b/3; 76% vs. 75%). Older patients had more complications during hospitalization (41% vs. 24%, p=0.034), higher 3-month mRS values (4.0±2.3 vs. 2.8±1.9, p<0.01), fewer favorable mRS values (mRS≤2: 27% vs. 52%, p<0.01), and higher 3-month (46% vs. 10% p<0.01) and 1-year mortality (49% vs. 11%, p<0.01). The NNT to achieve an additional patient with an independent outcome (mRS≤2) was 12 among older and six among younger patients. CONCLUSION: Despite a poor recovery rate, octogenarians benefitted from EVT for AIS, with a NNT comparable to that of younger patients treated with intravenous r-tPA.

Gadoterate meglumine decreases ADC values of breast lesions depending on the b value combination.

To retrospectively evaluated the influence of administration of the gadolinium based intravenous contrast agent (G-CA) on apparent diffusion coefficient (ADC) values in ADC maps generated using multiple b value combinations. A total of 106 women underwent bilateral 3.0 T breast MRI. As an internal validation, diffusion-weighted imaging (b values of 0, 200, 400, 600, 800 s/mm2) was performed before and after the G-CA (gadoterate meglumine (0.2 ml/kg, 3 ml/s)). Whole lesion and fibroglandular tissue (FGT) covering region-of-interests (ROIs) were drawn on the b = 800 s/mm2 images; ROIs were then propagated to multiple retrospectively generated ADC maps. Twenty-seven patients (mean age 55.8 ± 10.8 years) with 32 mass-like enhancing breast lesions including 25 (78.1 %) histopathologically malignant lesions were enrolled. Lesion ADC values were statistically significantly higher in pre-G-CA than post-G-CA ADC maps (ADC0,200,400,600,800: 1.05 ± 0.35 × 10-3 mm2/s vs. 1.02 ± 0.36 × 10-3 mm2/s (P < 0.05); ADC0,200,400: 1.25 ± 0.42 × 10-3 mm2/s vs. 1.20 ± 0.35 × 10-3 mm2/s (P < 0.05)). ADC values between pre- and post-contrast maps were not statistically different when the maps were generated using other b value combinations. Contrast agent administration did not affect the FGT ADC values. G-CA statistically significantly reduced the ADC values of breast lesions on ADC maps generated using the clinically widely utilized b values.

vWF correlates with visceral and pericardial adipose tissue in patients with a recent stroke of suspected cardiogenic etiology.

AIMS: A chronically elevated level of von Willebrand factor (vWF) is a common finding in patients with cardiovascular diseases. Obesity is a well-recognized risk factor for thrombotic cardiovascular complications including ischemic stroke, and it has been linked with increased plasma vWF. We evaluated whether elevated plasma levels of vWF associate with areas of visceral (VAT), pericardial (PAT), and subcutaneous adipose tissue (SAT) compartments in patients with acute/subacute stroke. METHODS AND RESULTS: A total of 69 patients with stroke of suspected cardiogenic etiology were examined. The plasma level of vWF antigen (vWF-ag) was measured both in the acute phase and in the chronic phase three months after stroke. The areas of VAT and/or PAT were assessed with computed tomography. As expected, in stroke patients, the levels of plasma vWF-ag were significantly higher than in the national reference population both in the acute and in the chronic phase. The level of vWF-ag in the chronic phase correlated with the amounts of VAT and PAT, but not with subcutaneous adipose tissue. CONCLUSIONS: These results agree with previous observations of the chronic inflammation/prothrombotic tendency in patients with cerebrovascular disease. Future studies should seek to clarify the role of visceral type adipose tissue in the pathophysiology of ischemic stroke.

Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year Mortality in Ischemic Stroke and TIA.

AIM: We evaluated soluble urokinase-type plasminogen activator receptor (suPAR) levels in different stroke subtypes and assessed their prognostic value regarding 5-year outcomes. MATERIALS AND METHODS: The study included 117 stroke patients (81 males; mean=age 61±11 years) with suspected cardioembolic stroke whose plasma suPAR concentration was assessed. Altogether, 20 (17.1%) patients suffered from stroke as a result of cardioembolism, 12 (10.3%) from large-artery atherosclerosis, 9 (7.7%) from small-vessel disease, 11 (9.4%) from both large-artery and cardioembolic etiology, and 65 (55.6%) had cryptogenic stroke. The mean follow-up period was 5 years. RESULTS: suPAR concentration was higher in patients who suffered from stroke/transient ischemic attack due to large-artery atherosclerosis (3.2±0.9 ng/ml) compared to small-vessel disease (2.0±0.5 ng/ml, p<0.001). An elevated plasma suPAR concentration was associated with all-cause mortality during the follow-up period (p=0.003). CONCLUSION: Elevated plasma suPAR concentrations predicted all-cause mortality during the 5-year follow-up after ischemic stroke. suPAR was not able to differentiate patients with cardioembolic stroke from those with other stroke types.

Morphological features of the left atrial appendage in consecutive coronary computed tomography angiography patients with and without atrial fibrillation.

The majority of intracardiac thrombi form in the left atrial appendage (LAA). Enlargement of this structure, together with certain morphological features, may indicate a predisposition to the formation of thrombi and subsequent cardioembolic stroke. Thus far, studies on LAA morphology have largely focused on those patients with atrial fibrillation (AF). Taking a different approach, we investigated the variation in LAA morphology in a consecutive patient population with and without AF. We evaluated 808 consecutive patients (529 females; mean age 52.5±9.9 years) who underwent coronary artery computed tomography angiography (CCTA), the majority of whom (749) had no history of AF. We assessed the length, lobe number, and morphological classification of their LAAs. Demographic data and medical histories were collated from medical records and then correlated with LAA morphology. The proportions of each of the four morphological classes of LAA for the overall vs. non-AF population were: WindSock, 62.3/61.5%; Cactus, 18.6/18.8%; ChickenWing, 10.0/10.0%; and CauliFlower, 9.2/9.6%. Age (p<0.001; r = 0.156) and female gender (p<0.001) were both found to be associated with an increased body surface area (BSA)-related LAA length. Male patients were more likely to manifest multi-lobed (p = 0.003) LAAs, and overweight patients with a greater number of multi-lobed LAA morphological classes (p = 0.010). No associations with morphological LAA features could be found for patients with diabetes, hypertension, or dyslipidemia. Nor did the size of the left atrium exhibit any correlation with BSA-related LAA length. In the overall and non-AF populations, aging and female gender were associated with longer BSA-indexed LAAs.

Cardiac CT Differentiates Left Atrial Appendage Thrombi from Circulatory Stasis in Acute Stroke Patients.

BACKGROUND/AIM: The left atrial appendage (LAA) is the most typical origin for a cardioembolic thrombusins' stroke etiology. Although transesophageal echocardiography (TEE) is widely used, this technique encounters difficulties in differentiating solid thrombus from circulatory stasis/spontaneous echo contrast (SEC). We assessed whether cardiac computed tomography (cCT) could more accurately detect LAA thrombi. MATERIALS AND METHODS: A total of 102 patients with suspected acute cardioembolic stroke/ transient ischemic attack (TIA) without chronic atrial fibrillation underwent arterial and venous phase cCT and TEE. TEE and cCT were consensus read to define LAA thrombus, while TEE alone was used to determine SEC. The LAA/aorta Houndsfield unit (HU) ratio was measured in both phases independently and blinded to prior visual readings. The optimal LAA/aorta HU ratio cut-off value for differentiating thrombi and SEC was estimated. RESULTS: TEE indicated 10 SECs and three thrombi. Consensus reading of cCT and TEE indicated that all thrombi detected in TEE were false-positive but revealed three actual thrombi missed in TEE. The LAA/aorta HU ratio correlated significantly with the presence of SEC both in arterial (p=0.019) and venous phases (p=0.024) and with the presence of thrombi in both phases (p<0.001). The best trade-off values for LAA/aorta HU ratio for the detection of thrombi was <0.245 in both phases. SEC was characterized with HU ratios of >0.245 and <0.577 in the arterial phase and>0.245 and <0.824 in the venous phase. Values of sensitivity, specificity, positive and negative predictive value and accuracy for detection of thrombi were 100% for cCT in both phases. CONCLUSION: cCT is more accurate than TEE in the detection of LAA thrombi, especially when combined with the measurement of LAA/aorta HU ratio.