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.

Computed tomography and echocardiography together reveal more high-risk findings than echocardiography alone in the diagnostics of stroke etiology.

BACKGROUND: Cardioembolic stroke carries a major risk of stroke recurrence, which can be markedly reduced by early initiation of appropriate secondary prevention. We investigate whether combined examination of the heart, aorta, and cervicocranial arteries with computed tomography (CACC-CT) may improve the diagnosis of stroke etiology. METHODS: Patients with suspected cardiogenic ischemic stroke or transient ischemic attack (n = 140; mean age 60 ± 10 years; 95 males) underwent CACC-CT and standard diagnostics including transthoracic and transesophageal echocardiography (TTE/TEE). Patients with atrial fibrillation were excluded because cardiac imaging will not affect to anticoagulant treatment. Imaging findings with a potential cardioembolic source were analyzed. Aortic and cardiac risk findings were evaluated independently. Consensus reading of 2 experts using the findings of both approaches and complemented by cardiac MRI when needed served as the reference standard. RESULTS: In 101 patients (72%) the clinical diagnosis was stroke, and transient ischemic attack was confirmed in the remaining patients. Imaging findings associated with highly increased cardioembolic risk were detected in 22 patients (16%). Nine high-risk findings in 140 patients were found by TTE/TEE and this number rose to 25 high after performing both echocardiography and CACC-CT. No difference was found between CACC-CT and TTE/TEE in detecting patients with of at least one high-risk findings (sensitivity 68 vs. 41%, p = 0.052; specificity 98 vs. 99%; overall accuracy 94 vs. 90%). Combined use of CACC-CT and TTE/TEE was more sensitive than TTE/TEE alone for detecting patients with at least one cardiac or aortic high-risk finding (sensitivity 91 vs. 41%, p < 0.001; specificity 98 vs. 99%; overall accuracy 97 vs. 90%). TTE/TEE was insufficient for diagnosing myocardial infarction with left ventricular aneurysm, whereas the accuracy of CACC-CT was high. In 9 patients (6%) with normal or mild hypokinesia in TTE/TEE, CACC-CT and MRI showed myocardial infarction large enough to indicate anticoagulant therapy. In contrast, CACC-CT was not suitable for diagnosing small left artrial thrombi, patent foramen ovale or to measure left ventricular ejection fraction. CONCLUSION: CACC-CT and TTE/TEE alone show limited accuracy for the diagnostics of stroke etiology. Therefore, CACC-CT could be a valuable tool in patients with cryptogenic stroke despite standard stroke diagnostics.

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.

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.

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.

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.

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.

Increased visceral adipose tissue as a potential risk factor in patients with embolic stroke of undetermined source (ESUS).

PURPOSE: The etiology of an ischemic stroke remains undetermined in 20-35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke. METHODS: Altogether 58 patients (mean age 57.7 ± 10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered. RESULTS: Mean VAT area was significantly higher in stroke patients (205 ± 103 cm2 for men and 168 ± 99 cm2 for women) compared to all reference populations (P < 0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors. CONCLUSION: Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.