Prediction of functional outcome using the novel asymmetric middle cerebral artery index in cryptogenic stroke patients

BACKGROUND: Etiology is unknown in approximately one-quarter of stroke patients after evaluation, which is termed cryptogenic stroke (CS). The prognosis of CS patients is largely undetermined. We created a novel index from transcranial Doppler parameters including mean flow velocity (MV) and pulsatility index (PI) and investigated whether the calculation of asymmetry in the novel parameter can predict functional outcomes in CS patients. METHODS: We made the middle cerebral artery (MCA) index (%) as a novel parameter, which was calculated as 100 X (MCA MV + MCA PI X 10) / (MCA MV-MCA PI X 10). The MCA asymmetry index (%) was also calculated as 100 X (Rt MCA index-Lt MCA index) / (Rt MCA index + Lt MCA index) / 2. Poor functional outcomes were defined as modified Rankin Scale score (mRS) ≥3 at 3 months after stroke onset. RESULTS: A total of 377 CS patients were included. Among them, 52 (13.8%) patients had a poor outcome. The overall MCA asymmetry index was two-fold higher in CS patients with a poor outcome (10.26%) compared to those with a good outcome (5.41%, p = 0.002). In multivariable analysis, the overall MCA asymmetry index (OR, 1.054, 95% CI, 1.013-1.096, p = 0.009) and the cutoff value of the overall MCA asymmetry index >9 were associated with poor outcomes at 3 months (OR, 3.737, 95% CI, 1.530-9.128, p = 0.004). CONCLUSION: We demonstrated that the novel asymmetric MCA index can predict short-term functional outcomes in CS patients.ope

Impact of Non-vitamin K Antagonist Oral Anticoagulant Withdrawal on Stroke Outcomes

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF). Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groups Results: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1-17)], followed by the warfarin withdrawal group [11, IQR (1-14, 18)], the no antithrombotic group [5, IQR (1-13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1-10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384-8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group. Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes.ope

Body Mass Index and Prognosis in Ischemic Stroke Patients With Type 2 Diabetes Mellitus

Background: Overweight contributes to type 2 diabetes mellitus (T2DM) development. Although the obesity paradox has been suggested in many vascular diseases, little information is available about stroke patients with T2DM. We investigated whether body mass index (BMI) has a differential impact on the incidence of major adverse cardiovascular events (MACE) in patients with ischemic stroke and T2DM. Methods: This retrospective study used a prospective cohort of patients with acute ischemic stroke and included consecutive patients with T2DM after excluding those with active cancer or who died within 1 month of an index stroke. We investigated the long-term risk of MACE (stroke, myocardial infarction, unstable angina, coronary revascularization procedure, and death) according to BMI. Results: Among the 1,338 patients, MACE occurred in 415 patients (31.1%) during a median follow-up of 3.6 years. Compared to the normal weight group, MACE occurred more frequently in the underweight group [adjusted hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.01-2.38], but less frequently in the overweight group (adjusted HR: 0.87, 95% CI: 0.70-1.08) and obese group (adjusted HR: 0.58, 95% CI: 0.41-0.86) group. In analyses of association between BMI and each component of MACE, stroke and cardiovascular mortality indicated an L- and a U-shaped pattern, respectively. However, fatal or non-fatal stroke showed an inverse pattern, and fatal or non-fatal cardiovascular events showed a reversed J-shaped pattern. Discussions: This study showed the overall presence of the obesity paradox in stroke patients with T2DM. However, obese patients had different risks of cardiovascular events and stroke.ope

Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis

BACKGROUND: The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH. METHODS: We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6-9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3. RESULTS: Among 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12-2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15-2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association. CONCLUSION: The degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.ope

Impact of the Total Number of Carotid Plaques on the Outcome of Ischemic Stroke Patients with Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) shares several risk factors with atherosclerosis. We investigated the association between total carotid plaque number (TPN) and long-term prognosis in ischemic stroke patients with AF. METHODS: A total of 392 ischemic stroke patients with AF who underwent carotid ultrasonography were enrolled. TPN was assessed using B-mode ultrasound. The patients were categorized into two groups according to best cutoff values for TPN (TPN ≤ 4 vs. TPN ≥ 5). The long-term risk of major adverse cardiovascular events (MACE) and mortality according to TPN was investigated using a Cox hazard model. RESULTS: After a mean follow-up of 2.42 years, 113 patients (28.8%) had developed MACE and 88 patients (22.4%) had died. MACE occurred more frequently in the TPN ≥ 5 group than in the TPN ≤ 4 group (adjusted hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.01-2.21; p < 0.05). Moreover, the TPN ≥ 5 group showed an increased risk of all-cause mortality (adjusted HR, 2.69; 95% CI, 1.40-5.17; p < 0.05). TPN along with maximal plaque thickness and intima media thickness showed improved prognostic utility when added to the variables of the CHAD2DS2-VASc score. CONCLUSION: TPN can predict the long-term outcome of ischemic stroke patients with AF. Adding TPN to the CHAD2DS2-VASc score increases the predictability of outcome after stroke.ope

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis

Background and purpose: Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known. Methods: We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up. Results: Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P<0.001). In a multivariate Cox proportional hazard analysis, the presence of NBTE was independently associated with composite outcomes of mortality and stroke events (hazard ratio, 1.941; 95% confidence interval, 1.052 to 3.690). Conclusions: NBTE should be suspected as a potential cause of stroke in patients with metastatic cancer. Patients with NBTE have a high risk of recurrent stroke and mortality. Future studies are necessary to determine strategies to reduce stroke recurrence in patients with NBTE.ope

Impact of Sarcopenia on Functional Outcomes Among Patients With Mild Acute Ischemic Stroke and Transient Ischemic Attack: A Retrospective Study

Introduction: Sarcopenia, a age-related disease characterized by loss of muscle mass accompanied by loss of function, is associated with nutrition imbalance, physical inactivity, insulin resistance, inflammation, metabolic syndrome, and atherosclerosis which are risk factors for cardiovascular disease. However, its association with outcomes after ischemic stroke has not been well-established. This study investigated whether functional outcomes of patients with acute ischemic stroke is associated with sarcopenia. Methods: Data were collected from 568 consecutive patients with acute ischemic stroke with National Institute of Health Stroke Scale 0-5 or transient ischemic attack who underwent bioelectrical impedance analysis between March 2018 and March 2021. Sarcopenia was defined, as low muscle mass, as measured by bioelectrical impedance analysis, and low muscle strength, as indicated by the Medical Research Council score. Unfavorable functional outcome was defined as mRS score of 2-6 at 90 days after discharge. The relationship between functional outcomes and the presence of sarcopenia or its components was determined. Results: Of the 568 patients included (mean age 65.5 ± 12.6 years, 64.6% male), sarcopenia was detected in 48 (8.5%). After adjusting for potential confounders, sarcopenia was independently and significantly associated with unfavorable functional outcome (odds ratio 2.37, 95% confidence interval 1.15-4.73 for unfavorable functional outcome, odds ratio 2.10, 95% confidence interval 1.18-3.71 for an increase in the mRS score). Each component of sarcopenia was also independently associated with unfavorable functional outcome (odds ratio 1.76, 95% confidence interval 1.05-2.95 with low muscle mass, odds ratio 2.64, 95% confidence interval 1.64-4.23 with low muscle strength). The impact of low muscle mass was larger in men than in women, and in patients with lower muscle mass of the lower extremities than in those with lower muscle mass of the upper extremities. Conclusions: In this study, the prevalence of sarcopenia in patients with stroke was lower than most of previous studies and patients with sarcopenia showed higher likelihood for unfavorable functional outcomes at 90 days after acute ischemic stroke or TIA. Further investigation of the interventions for treating sarcopenia and its impact on the outcome of ischemic stroke patients is needed.ope

Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation

Background and objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment. Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively. Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions: Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.ope

Improving the Clinical Outcome in Stroke Patients Receiving Thrombolytic or Endovascular Treatment in Korea: From the SECRET Study

We investigated whether there was an annual change in outcomes in patients who received the thrombolytic therapy or endovascular treatment (EVT) in Korea. This analysis was performed using data from a nationwide multicenter registry for exploring the selection criteria of patients who would benefit from reperfusion therapies in Korea. We compared the annual changes in the modified Rankin scale (mRS) at discharge and after 90 days and the achievement of successful recanalization from 2012 to 2017. We also investigated the determinants of favorable functional outcomes. Among 1230 included patients, the improvement of functional outcome at discharge after reperfusion therapy was noted as the calendar year increased (p < 0.001). The proportion of patients who were discharged to home significantly increased (from 45.6% in 2012 to 58.5% in 2017) (p < 0.001). The successful recanalization rate increased over time from 78.6% in 2012 to 85.1% in 2017 (p = 0.006). Time from door to initiation of reperfusion therapy decreased over the years (p < 0.05). These secular trends of improvements were also observed in 1203 patients with available mRS data at 90 days (p < 0.05). Functional outcome was associated with the calendar year, age, initial stroke severity, diabetes, preadmission disability, intervals from door to reperfusion therapy, and achievement of successful recanalization. This study demonstrated the secular trends of improvement in functional outcome and successful recanalization rate in patients who received reperfusion therapy in Korea.ope

D‐Dimer Level After Endovascular Treatment Can Help Predict Outcome of Acute Ischemic Stroke

Background : d‐Dimer level is a marker of hypercoagulability, which is associated with thrombus formation and resolution. We investigated the value of d‐dimer levels in predicting outcomes of acute ischemic stroke in patients who underwent endovascular treatment (EVT). Methods : We analyzed data of patients who underwent only EVT from the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) registry. d‐Dimer levels were routinely measured in 10 of 15 participating hospitals. Patients were grouped into tertiles (tertile 1, tertile 2, and tertile 3) according to d‐dimer levels (lowest, moderate, and highest, respectively). We compared serial scores on the National Institutes of Health Stroke Scale at baseline, on day 1 of hospitalization, and at discharge; functional outcome 3 months after EVT; and rate of mortality within 6 months after EVT. Results : In the 170 patients, the median d‐dimer level was 477 ng/mL (interquartile range, 249–988 ng/mL). In tertile 3, the National Institutes of Health Stroke Scale score was higher at discharge than on day 1 of hospitalization. Poor outcome 3 months after EVT (modified Rankin Scale score, ≥3) was more common with high d‐dimer levels (26.3% of tertile 1, 57.1% of tertile 2, and 76.4% of tertile 3; P<0.001). Multivariable analysis showed that a high d‐dimer level was independently associated with poor outcome 3 months after EVT (odds ratio [OR], 4.399 [95% CI, 1.594–12.135]). Kaplan–Meier survival analysis showed that a high d‐dimer level was independently associated with death within 6 months after EVT (OR, 5.441 [95% CI, 1.560–18.978]; log‐rank test, P<0.001). The d‐dimer effect showed no heterogeneity across the subgroups for poor outcome 3 months after EVT or death within 6 months after EVT. The direction of effect was unfavorable for tertile 3 across all demographic strata. Conclusions : High plasma d‐dimer levels were predictive of early neurologic worsening, poor functional outcome 3 months after EVT, and death within 6 months after EVT.ope