Thromboelastography-guided antiplatelet therapy for patients with ischemic cerebrocardiovascular diseases: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: 10 studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR 0.45, 95% CI 0.27 to 0.75, P=0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR 0.26, 95% CI 0.19 to 0.37; P<0.00001), ischemic events (OR 0.28, 95% CI 0.19 to 0.41; P<0.00001), and bleeding events (OR 0.31, 95% CI 0.16 to 0.62; P=0.0009) in patients with IS or CAD. CONCLUSIONS: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign.

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

Clinically Ineffective Reperfusion After Endovascular Therapy in Acute Ischemic Stroke.

Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion. However, in clinical practice, nearly half of the patients do not have favorable outcomes despite successful recanalization of the occluded artery. This unfavorable outcome can be defined as having clinically ineffective reperfusion. The objective of the review is to describe clinically ineffective reperfusion after endovascular therapy and its underlying risk factors and mechanisms, including initial tissue damage, cerebral edema, the no-reflow phenomenon, reperfusion injury, procedural features, and variations in postprocedural management. Further research is needed to more accurately identify patients at a high risk of clinically ineffective reperfusion after endovascular therapy and to improve individualized periprocedural management strategies, to increase the chance of achieving favorable clinical outcomes.

Associations of hematological and biochemical markers with intracranial atherosclerotic stenosis in stroke-free populations: A systematic review and meta-analysis of observational studies.

BACKGROUND AND AIMS: Intracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack. We aimed to synthesize relevant evidence on the associations of hematological and biochemical markers with ICAS in stroke-free populations. METHODS AND RESULTS: We searched MEDLINE and EMBASE for articles reporting associations of hematological and biochemical markers with ICAS presence in stroke-free populations. Weighted mean difference (WMD) and 95% confidence interval (CI) for each biomarker were pooled using fixed- or random-effects models. Among 32 studies included in the systematic review, 23 studies (48,326 subjects) with 22 biomarkers were meta-analyzed. Compared with subjects without ICAS, those with ICAS had significantly higher white blood cell (4118 subjects, WMD 0.28 per 109/L, 95% CI 0.01-0.56), neutrophil (4326 subjects, WMD 0.24 per 109/L, 0.10-0.38), neutrophil/lymphocyte ratio (4326 subjects, WMD 0.16, 0.07-0.26), low-density lipoprotein (28,606 subjects, WMD 0.12 mmol/L, 0.05-0.19), non-high-density lipoprotein (3671 subjects, WMD 0.17 mmol/L, 0.08-0.25), C-reactive protein (CRP; 5355 subjects, WMD 0.06 mg/dL, 0.04-0.07), high-sensitivity CRP (9383 subjects, WMD 0.07 mg/dL, 0.01-0.13), uric acid (5966 subjects, WMD 17.91 µmol/L, 11.16-24.66), creatinine (5731 subjects, WMD 4.03 µmol/L, 0.77-7.29), and homocysteine (7053 subjects, WMD 2.25 µmol/L, 1.02-3.48), but lower lymphocyte (4326 subjects, WMD -0.12 per 109/L, -0.19--0.04). Sensitivity analyses showed similar results. CONCLUSIONS: Several hematological and biochemical markers easily accessible were associated with ICAS presence in stroke-free populations. This can facilitate early identification of subjects at a high risk of ICAS, who may benefit from ICAS screening and prevention. PROSPERO REGISTRATION NUMBER: CRD42021247990.

Small vessel disease burden may not portend unfavorable outcome after thrombectomy for acute large vessel occlusion.

OBJECTIVES: We aimed to investigate the correlation between an overall cerebral small vessel disease (CSVD) burden and outcomes after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: In a multicenter registry study, we enrolled patients with EVT for anterior-circulation LVO-stroke. In 3.0-T MR imaging, we assessed 4 CSVD imaging markers, lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces, each assigned a score of 0 or 1 and summed up to an overall CSVD burden score of 0-4. We dichotomized the overall CSVD severity as none to mild (score 0-2) and moderate to severe (3-4). Primary outcome was 90-day functional dependence or death (modified Rankin Scale (mRS) 3-6). Secondary outcomes included increase in NIH Stroke Scale ≥ 4 within 24 h (early neurological deterioration (END)) and within 7 days, symptomatic intracranial hemorrhage, 90-day mRS 2-6, and 90-day mortality. RESULTS: Among 311 patients (63.0% male; mean age 65.1 ± 12.7 years), 260 (83.6%) had none-to-mild and 51 (16.4%) had moderate-to-severe overall CSVD burden. Moderate-to-severe CSVD burden was not significantly associated with the primary outcome (47.1% versus 45.4%; p > 0.05 in univariate and multivariate logistic regression), or the secondary outcomes except for a higher risk of END (11.8% versus 3.1%; p < 0.05 in multivariate analyses). Sensitivity analyses with 0-1 versus 2-4 of the CSVD burden score, and the score as an ordinal variable, showed similar results. CONCLUSIONS: An overall moderate-to-severe CSVD burden was not associated with 90-day functional dependence or death, after EVT for anterior-circulation LVO. TRIAL REGISTRATION: ChiCTR1900022154 KEY POINTS: • Moderate-to-severe cerebral small vessel disease burden on MRI should not be an exclusion indicator in determining the eligibility of an acute ischemic stroke patient for endovascular treatment.

Arterial blood gas analysis aids early differential diagnosis and treatment of primary and secondary hypokalaemic periodic paralysis.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p<0.001); they had higher pH (p=0.046) and HCO3 levels (p=0.014) at baseline, and needed a higher dose of potassium supplement before the serum potassium level returned to normal (p=0.007) and a longer time to regain full muscle strength (p=0.004), compared with those with primary or thyrotoxic HypoPP. Emergent arterial blood gas analysis may aid early differential diagnosis of patients with primary and secondary HypoPP.

Intraluminal Thrombus and Outcomes of Patients With Acute Large Vessel Occlusive Stroke Undergoing Endovascular Treatment.

BACKGROUND AND PURPOSE: Intraluminal thrombus (ILT) is an emerging imaging marker in acute ischemic stroke. We aimed to investigate the association of ILT with outcomes of acute large vessel occlusion (LVO) patients receiving endovascular treatment. METHODS: Acute LVO stroke patients who underwent endovascular treatment within 24 hours, in a prospective, nationwide registry were enrolled. Pretreatment digital subtraction angiography was reviewed for the presence of ILT. The primary outcome was 90-day functional dependence (modified Rankin Scale scores, 3-6). Secondary outcomes included 24-hour LVO, 90-day death, and symptomatic intracranial hemorrhage. RESULTS: Among 711 patients enrolled, 75 (10.5%) with ILT were less likely to have 90-day functional dependence compared with those without ILT (adjusted odds ratio, 0.53 [95% CI, 0.31-0.90]; P=0.021). The same trend was found among those with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3; P=0.008) but not in those without successful reperfusion (P=0.107). Presence of ILT was also independently associated with a lower rate of 24-hour LVO (adjusted odds ratio 0.34 [95% CI, 0.13-0.89]; P=0.028). However, those with or without ILT had similar risks of symptomatic intracranial hemorrhage and 90-day death. CONCLUSIONS: Among acute LVO patients receiving endovascular treatment, pretreatment ILT-positive patients may have a better 90-day functional outcome (versus ILT-negative) but similar risk of death and symptomatic intracranial hemorrhage. The possibly favorable effect of ILT patients remained in those with successful reperfusion. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Intracranial arterial stenosis in Caucasian versus Chinese patients with TIA and minor stroke: two contemporaneous cohorts and a systematic review.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of stroke worldwide. Separate reports in Caucasians and Asians with stroke/transient ischaemic attack (TIA) have suggested lower ICAS prevalence in Caucasians, but there has been no direct comparisons of the two ethnic groups with the same criteria to define ICAS. METHODS: Acute minor stroke or TIA patients in two cohorts respectively recruiting patients in Oxford (2011-2018, predominantly Caucasians) and Hong Kong (2011-2015, predominantly Chinese) were compared. ICAS was defined as ≥50% stenosis/occlusion in any major intracranial artery in MR/CT angiography. Prevalence, distribution and risk factors of ICAS were compared between the two cohorts. We also systematically reviewed literature on ICAS prevalence in stroke/TIA patients in different populations. RESULTS: Among 1287 patients from Oxford and 691 from Hong Kong (mean age 69 vs 66), ICAS prevalence was higher in Chinese than in Caucasians (43.0% vs 20.0%; OR 3.02; 95% CI 2.47 to 3.70; p<0.001), independent of age (age-adjusted OR 3.73; 95% CI 3.00 to 4.63; p<0.001) and vascular risk factors (multivariable-adjusted OR 3.21; 95% CI 2.56 to 4.02; p<0.001). This ethnic difference was greater (p interaction=0.005) at age <70 years (OR 5.33; 95% CI 3.79 to 7.50; p<0.001) than at ≥70 years (OR 2.81; 95% CI 2.11 to 3.74; p<0.001). ICAS prevalence increased with age and with vascular risk factors in both cohorts, with equivalent prevalence in Chinese aged <60 years and Caucasians aged ≥80, and in Chinese with no vascular risk factor and Caucasians with two vascular risk factors. ICAS locations also differed between Chinese and Caucasian patients. CONCLUSIONS: Chinese are more susceptible to ICAS than Caucasians, with an earlier onset age and a higher prevalence, independent of vascular risk factors.

Translesional Pressure Gradient Alters Relationship Between Blood Pressure and Recurrent Stroke in Intracranial Stenosis.

Background and Purpose- There is debate over an optimal systolic blood pressure (SBP) in secondary stroke prevention of patients with symptomatic intracranial atherosclerotic stenosis (sICAS). We investigated whether translesional pressure gradient across sICAS would alter the relationship between SBP and risk of recurrent stroke in such patients. Methods- We recruited patients with sICAS (50%-99% stenosis) confirmed in computed tomography angiography. We simulated blood flow across sICAS with computed tomography angiography-based computational fluid dynamics models. Translesional pressure ratio (PR=Pressurepost-stenotic/Pressurepre-stenotic) was calculated in each case. Pressure ratio (PR) ≤ median was defined as low PR, indicating larger translesional pressure gradient across sICAS. All patients received optimal medical treatment. We investigated the interaction of translesional PR and mean SBP during follow-up (SBPFU) in determining the risk of the primary outcome, recurrent ischemic stroke in the same territory within 1 year. Results- Among 157 patients with sICAS, the median PR was 0.93. Multivariate Cox regression revealed significant PR-SBPFU interaction on the primary outcome (P=0.008): in patients with normal PR, risk of primary outcome significantly decreased with lower SBPFU (hazard ratio for 10 mm Hg decrement =0.46; P=0.018); however, in those with low PR, SBPFU≤130 mm Hg was associated with significantly increased risk of primary outcome, compared with 130

Cortical Microinfarcts Associated With Worse Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment.

BACKGROUND AND PURPOSE: We aimed to evaluate the impact of cortical microinfarcts (CMIs) on functional outcome after endovascular treatment in patients with acute ischemic stroke. METHODS: In a multicenter registration study for RESCUE-RE (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization), eligible patients with large vessel occlusion stroke receiving endovascular treatment, who had undergone 3T magnetic resonance imaging on admission or within 24 hours after endovascular treatment were analyzed. We evaluated the presence and numbers of CMIs with assessment of axial T1, T2-weighted images, and fluid-attenuated inversion recovery images. The primary outcome was functional dependence or death defined as modified Rankin Scale scores of 3 to 6 at 90 days. Secondary outcomes included early neurological improvement, any intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality. We investigated the independent associations of CMIs with the outcomes using multivariable logistic regression in overall patients and in subgroups. RESULTS: Among 414 patients (enrolled from July 2018 to May 2019) included in the analyses, 96 (23.2%) patients had at least one CMI (maximum 6). Patients with CMI(s) were more likely to be functionally dependent or dead at 90 days, compared with those without (55.2% versus 37.4%; P<0.01). In multivariable logistic regression analyses, presence of CMI(s) (adjusted odds ratio, 1.78 [95% CI, 1.04-3.07]; P=0.04) and multiple CMIs (CMIs ≥2; adjusted odds ratio, 7.41 [95% CI, 2.48-22.17]; P<0.001) were independently, significantly associated with the primary outcome. There was no significant difference between subgroups in the associations between CMI presence and the primary outcome. CONCLUSIONS: Acute large vessel occlusion stroke patients receiving endovascular treatment with CMI(s) were more likely to have a poor functional outcome at 90 days, independent of patients' characteristics. Such associations may be dose-dependent. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated. METHODS: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed. RESULTS: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year. CONCLUSIONS: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.

Hemodynamics and stroke risk in intracranial atherosclerotic disease.

OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. RESULTS: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). INTERPRETATION: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Disease: Classification and Clinical Implications.

Background and Purpose- In patients with symptomatic intracranial atherosclerotic stenosis, identifying the underlying stroke mechanisms may inform secondary prevention. We aimed to propose reproducible classification criteria for stroke mechanisms based on routine neuroimaging in symptomatic intracranial atherosclerotic stenosis and explore their clinical implications. Methods- We recruited patients with acute ischemic stroke attributed to 50% to 99% intracranial atherosclerotic stenosis in anterior circulation from 2 centers. Two investigators independently classified probable stroke mechanisms as parent artery atherosclerosis occluding penetrating artery, artery-to-artery embolism, hypoperfusion, and mixed mechanisms, with prespecified criteria based on infarct topography and magnetic resonance/computed tomography angiography. These stroke mechanisms were correlated with features of the patients at baseline and recurrent ischemic stroke in the same territory or relevant transient ischemic attack within 1 year. Results- Among 153 patients recruited, the most common stroke mechanisms were isolated hypoperfusion (35.3%) and mixed mechanism of artery-to-artery embolism and hypoperfusion (37.3%) that was associated with higher incidence of dyslipidemia (P=0.045) and hypertension (P=0.033) than patients with other stroke mechanisms. The proposed criteria showed substantial to excellent intrarater and interrater reproducibilities (κ, 0.791-0.908). Overall, 31 patients received interventional treatment of the diseased intracranial artery; 122 received medical treatment, among whom a mixed mechanism of artery-to-artery embolism and hypoperfusion at baseline was associated with higher risk of ischemic stroke in the same territory within 1 year (24.4% versus 7.8%; hazard ratio, 3.40; 95% CI, 1.25-9.20; log-rank P=0.010) than other mechanisms combined. Conclusions- Artery-to-artery embolism and hypoperfusion commonly coexist in ischemic stroke attributed to intracranial atherosclerotic stenosis, which may be associated with higher risk of stroke relapse.

Antiplatelet therapy after stroke: should it differ in the acute and chronic phase after stroke.

PURPOSE OF REVIEW: Reviewing existing evidence regarding well tolerated and effective antiplatelet treatment in patients with acute or chronic, noncardioembolic ischemic stroke and transient ischemic attack (TIA). RECENT FINDINGS: For patients with high-risk stroke or TIA, for instance, minor stroke or high-risk TIA, or stroke of atherosclerotic origin with evidence suggesting risk of artery-to-artery embolism or with high-grade, symptomatic arterial stenosis, early initiated, short-term dual antiplatelet (e.g. aspirin and clopidogrel) is effective in reducing the risk of recurrent stroke and other vascular events which does not increase the risk of severe or fatal bleeding, as compared with mono antiplatelet therapy. However, long-term application of aggressive antiplatelet therapies after a noncardioembolic stroke or TIA increases the bleeding risks. Triple antiplatelet therapy is not appropriate for noncardioembolic stroke or TIA, in view of the high bleeding risk. In addition, emerging antiplatelets such as ticagrelor and cilostazol may work better in certain subgroups of stroke patients, which warrants further investigation. SUMMARY: Antiplatelet therapies should differ in the acute and chronic phases among patients with high-risk stroke or TIA when more aggressive antiplatelet treatment is reasonable in the acute phase, but no solid evidence supports different antiplatelet strategies in acute and chronic phases in patients with low-risk noncardioembolic stroke.

Impact of Side Branches on the Computation of Fractional Flow in Intracranial Arterial Stenosis Using the Computational Fluid Dynamics Method.

BACKGROUND: Computational fluid dynamics (CFD) allows noninvasive fractional flow (FF) computation in intracranial arterial stenosis. Removal of small artery branches is necessary in CFD simulation. The consequent effects on FF value needs to be judged. METHODS: An idealized vascular model was built with 70% focal luminal stenosis. A branch with one third or one half of the radius of the parent vessel was added at a distance of 5, 10, 15 and 20 mm to the lesion. With pressure and flow rate applied as inlet and outlet boundary conditions, CFD simulations were performed. Flow distribution at bifurcations followed Murray's law. By including or removing side branches, five patient-specific intracranial artery models were simulated. Transient simulation was performed on a patient-specific model, with a larger branch for validation. Branching effect was considered trivial if the FF difference between paired models (branches included or removed) was within 5%. RESULTS: Compared with the control model without a branch, in all idealized models the relative differences of FF was within 2%. In five pairs of cerebral arteries (branches included/removed), FFs were 0.876 and 0.877, 0.853 and 0.858, 0.874 and 0.869, 0.865 and 0.858, 0.952 and 0.948. The relative difference in each pair was less than 1%. In transient model, the relative difference of FF was 3.5%. CONCLUSION: The impact of removing side branches with radius less than 50% of the parent vessel on FF measurement accuracy is negligible in static CFD simulations, and minor in transient CFD simulation.

Cortical Microinfarcts in Patients with Middle Cerebral Artery Stenosis.

BACKGROUND: Cortical microinfarcts (CMIs) have been correlated to cognitive decline and dementia. It was previously considered only visible on microscope, but was recently reported to be visible on 3.0 Tesla magnetic resonance imaging (MRI) and linked to presence of intracranial stenosis. We aimed to investigate CMIs on 3.0 Tesla MRI in patients with M1 middle cerebral artery (MCA-M1) stenosis. METHODS: Patients with a recent non-cardioembolic ischemic stroke or transient ischemic attack and an atherosclerotic MCA-M1 stenosis were recruited. The severity of MCA stenosis was defined as moderate (50%-69%) or severe (70%-99% or focal flow void) on time-of-flight MR angiography (MRA). The distal to proximal signal intensity ratio (SIR) of MCA stenosis was measured on time-of-flight MRA to represent its hemodynamic significance. The presence of CMI(s) in the ipsilateral hemisphere was assessed on axial T1- or T2-weighted images and T2-weighted fluid-attenuated inversion-recovery images. RESULTS: Overall, 86 patients (mean age: 62.8 years; 77.9% males) were analyzed, 66 (76.7%) and 20 (23.3%), respectively, having moderate and severe MCA-M1 stenoses. The median SIR was .91. Forty-five (52.3%) patients had ipsilateral CMI(s). Multivariate logistic regression showed a history of dyslipidemia (odds ratio [OR] = 6.83, P = .008), and an SIR lower than the median (OR = 4.73, P = .014) were independently associated with presence of CMI(s) in ipsilateral hemisphere to an MCA-M1 stenosis. CONCLUSIONS: Patients with stroke and intracranial stenosis had a high burden of CMI. Except for a history of dyslipidemia, the hemodynamic significance of the arterial stenosis may contribute to the presence of ipsilateral CMI(s) in these patients, which warrants further investigation in prospective, longitudinal studies.

Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis.

OBJECTIVE: We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions. METHODS: Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted. RESULTS: In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods. CONCLUSIONS: Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies.