Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults.

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).

Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Incidence and Risk Factors of Transient Global Amnesia.

INTRODUCTION: Transient global amnesia (TGA) is a spontaneously resolving, anterograde amnesia that lasts mostly <24 h and often occurs with retrograde amnesia. The etiology of TGA remains unclear, although in recent decades, many risk factors and preceding events have been identified. There are few up-to-date reports on the TGA incidence in Northern Europe. In this study, we report the incidence and risk factors associated with TGA in Finland. MATERIALS AND METHODS: The study included all patients with suspected TGA that were referred to Kuopio University Hospital (KUH) in 2017. The hospital catchment area included 246,653 individuals. Risk factors and demographic data were collected from medical records. The TGA incidence rates were calculated as the number of patients with TGA divided by the number of individuals at risk in different age groups. RESULTS: In 2017, 56 patients were treated for TGA at KUH. Of these, 46 had a first-ever TGA. The most common event preceding TGA was physical effort (n = 28, 50%), followed by emotional stress (n = 11, 19.6%) and water contact or a temperature change (n = 11, 19.6%). The most common comorbidities were hypercholesterolemia (n = 22, 39.3%), hypertensive disease (n = 21, 37.5%), hypothyroidism (n = 11, 19.6%), coronary artery disease (n = 8, 14.3%), and migraine (n = 7, 12.5%). TGA occurred most often in December (n = 9, 16.0%), March (n = 8, 14.3%), or October (n = 8, 14.3%), and least often in November and May (n = 2, 3.6% in both months). The crude incidence of a first TGA in Eastern Finland was 18.6/100,000 inhabitants, and when standardized to the European population in 2010, it was 14.3/100,000 inhabitants. Therefore, the TGA incidence was higher than previously reported in European countries. DISCUSSION: The most common precipitating factors for TGA were physical effort, emotional stress, and water contact/temperature change. The incidence of TGA was high in the Eastern Finnish population.

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults.

BACKGROUND: In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. PATIENTS AND METHODS: In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. RESULTS: 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. CONCLUSIONS: Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Incidence of first-ever transient ischemic attack in Eastern Finland.

OBJECTIVES: The incidence of stroke has been declining in Finland, as well as in Europe. However, it is unclear whether the incidence of transient ischemic attack (TIA) is also decreasing. In fact, the TIA incidence in the Finnish population has never been reported. Therefore, here we investigated the incidence of TIA in the Eastern Finnish population in 2017. MATERIALS AND METHODS: All patients with suspected TIA, from a defined catchment area, were referred to a neurological emergency unit at Kuopio University Hospital (KUH) in the Northern Savonia region of Eastern Finland, which had a population of 246,653 in 2017. The original study population comprised TIA patients diagnosed based on the WHO TIA criteria in 2017. Incidence rates were calculated by dividing the number of TIA cases by the number of people in different age groups. RESULTS: Among 432 patients with a suspected TIA referred to the neurological emergency unit at Kuopio University Hospital in 2017, 293 were living in Northern Savonia and were ultimately diagnosed with TIA after neurological examinations. The number of first-ever TIAs was 211. The crude incidence of all TIA was 122/100,000 inhabitants, and of first-ever TIA was 86/100,000. The age-standardized incidence (European population 2010) of the first-ever TIA was calculated to be 64/100,000. The mean age of first-ever TIA patients was 70 years: 72 years for women versus 68 years for men. CONCLUSIONS: We found a high incidence of TIA in Eastern Finland.

Primary central nervous system lymphoma high incidence and poor survival in Finnish population-based analysis.

BACKGROUND: We report here the first population-based incidence rates and prognosis of primary central nervous system lymphoma (PCNSL) in Finland. METHODS: Finnish Cancer Registry data by histological diagnosis and tumor location (2007-2017) for cases with diffuse large B-cell lymphoma. RESULTS: During 2007-2017, 392 new cases of PCNSL were reported (195 males, 197 females). The average age-adjusted incidence was 0.68/100,000 person-years. Incidence for males was 0.74/100,000 and for females 0.63/100,000, respectively. The incidence was highest, 2.93/100,000, among people aged 75-79 years. Concerning all cases in 2007-2017 the 2-year age-adjusted relative survival rate was 33% and the corresponding 5-year survival rate was 26%. Among patients under the age of 70, the age-adjusted 5-year relative survival rate increased from 36% in 2007-2012 to 43% for 2013-2017. Among patients aged 70+ the corresponding survival rates were poor, 7 and 9%. CONCLUSIONS: PCNSL incidence in Finland is among the highest reported in the world. The annual increase in incidence was 2.4%. The prognosis is still dismal, especially in elderly patients.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

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.

Neural network analysis of nocturnal SpO2 signal enables easy screening of sleep apnea in patients with acute cerebrovascular disease.

Current diagnostics of sleep apnea relies on the time-consuming manual analysis of complex sleep registrations, which is impractical for routine screening in hospitalized patients with a high probability for sleep apnea, e.g. those experiencing acute stroke or transient ischemic attacks (TIA). To overcome this shortcoming, we aimed to develop a convolutional neural network (CNN) capable of estimating the severity of sleep apnea in acute stroke and TIA patients based solely on the nocturnal oxygen saturation (SpO2) signal. The CNN was trained with SpO2 signals derived from 1379 home sleep apnea tests (HSAT) of suspected sleep apnea patients and tested with SpO2 signals of 77 acute ischemic stroke or TIA patients. The CNN's performance was tested by comparing the estimated respiratory event index (REI) and oxygen desaturation index (ODI) with manually obtained values. Median estimation errors for REI and ODI in patients with stroke or TIA were 1.45 events/hour and 0.61 events/hour, respectively. Furthermore, based on estimated REI and ODI, 77.9% and 88.3% of these patients were classified into the correct sleep apnea severity categories. The sensitivity and specificity to identify sleep apnea (REI > 5 events/hour) were 91.8% and 78.6%, respectively. Moderate-to-severe sleep apnea was detected (REI > 15 events/hour) with sensitivity of 92.3% and specificity of 96.1%. The CNN analysis of the SpO2 signal has great potential as a simple screening tool for sleep apnea. This novel automatic method accurately detects sleep apnea in acute cerebrovascular disease patients and facilitates their referral for a differential diagnostic HSAT or polysomnography evaluation.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

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.

The selection of an optimal transportation strategy in urgent stroke missions: a simulation study.

BACKGROUND: Stroke causes death, disability and increases the use of healthcare resources worldwide. The outcome of intravenous thrombolysis and mechanical endovascular thrombectomy highly depends on the delay from symptom onset to initiation of definitive treatment. The purpose of this study was to compare the various patient transportation strategies to minimize pre-hospital delays. METHODS: Emergency medical services (EMS) mission locations and ambulance response times in Finland with urgent stroke-suspected dispatch codes were collected from Emergency Response Centre (ERC) records between 1 January 2016 and 31 December 2016. Four transport scenarios were simulated for each mission, comparing ground and helicopter transportation to hospital with different treatment capabilities. RESULTS: In 2016, a total of 20,513 urgent stroke-suspected missions occurred in Finland. Of these, we were able to locate and calculate a route to scenario-based hospitals in 98.7% (20,240) of the missions. For ground transport, the estimated median pre-hospital time to a thrombolysis-capable and thrombectomy-capable hospital were 54.5 min (95% confidence interval (CI), 31.7-111.4) and 94.4 min (95% CI, 33.3-195.8), respectively. Should patients be transported on the ground to thrombectomy-capable hospitals only, the pre-hospital time would increase in 11,003 (54.4%) of missions, most of which were in rural areas. With the fastest possible transportation method, the estimated mean transport time to a thrombectomy-capable hospital was 80.84 min (median, 80.80 min; 95% CI, 33.3-143.1). Helicopter transportation was the fastest method in 68.8% (13,921) of missions, and the time saved was greater than 30 min in 27.1% (5475) of missions. In rural areas, helicopter transportation was the fastest option in nearly all missions if dispatched simultaneously with ground ambulance. CONCLUSION: Helicopter transportation may significantly decrease pre-hospital delays for stroke patients, especially in rural areas, but the selection of an optimal transportation method or chain of methods should be determined case-by-case.

Acute stroke and TIA patients have specific polygraphic features of obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is associated with increased risk for stroke, which is known to further impair respiratory functions. However, it is unknown whether the type and severity of respiratory events are linked to stroke or transient ischemic attack (TIA). Thus, we investigate whether the characteristics of individual respiratory events differ between patients experiencing TIA or acute ischemic stroke and matched patients with clinically suspected sleep-disordered breathing. METHODS: Polygraphic data of 77 in-patients with acute ischemic stroke (n = 49) or TIA (n = 28) were compared to age, gender, and BMI-matched patients with suspected sleep-disordered breathing and no cerebrovascular disease. Along with conventional diagnostic parameters (e.g., apnea-hypopnea index), durations and severities of individual apneas, hypopneas and desaturations were compared between the groups separately for ischemic stroke and TIA patients. RESULTS: Stroke and TIA patients had significantly shorter apneas and hypopneas (p < 0.001) compared to matched reference patients. Furthermore, stroke patients had more central apnea events (p = 0.007) and a trend for higher apnea/hypopnea number ratios (p = 0.091). The prevalence of OSA (apnea-hypopnea index ≥ 5) was 90% in acute stroke patients and 79% in transient ischemic attack patients. CONCLUSION: Stroke patients had different characteristics of respiratory events, i.e., their polygraphic phenotype of OSA differs compared to matched reference patients. The observed differences in polygraphic features might indicate that stroke and TIA patients suffer from OSA phenotype recently associated with increased cardiovascular mortality. Therefore, optimal diagnostics and treatment require routine OSA screening in patients with acute cerebrovascular disease, even without previous suspicion of OSA.

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.

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.

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design.

BACKGROUND: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. KEY HYPOTHESES/AIMS: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. DESIGN: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient-control pairs enrolled by the end of 2018. SUMMARY: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

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.