Shahripour, Reza Bavarsad

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Introduction: Mechanical thrombectomy (MT) is a primary treatment for acute ischemic stroke due to large vessel occlusions. While effective, 20-40% of patients experience hemorrhagic transformation (HT), and around 50% fail to achieve favorable functional outcomes. Transcranial Doppler (TCD) is a non-invasive and cost-effective method for real-time monitoring of hemodynamic status following MT. However, the prognostic value of TCD parameters in predicting HT and poor functional outcome is unclear. We performed a systematic review and meta-analysis of 4 TCD parameters (mean flow velocity (MFV), MFV index, peak systolic velocity (PSV), and pulsatility index (PI) in patients with and without HT and favorable vs poor functional recovery (modified Rankin Scale (mRS) 0-2 vs 3-6). Methods: PubMed, Embase, and Scopus were searched on July 25, 2024 to identify observational studies in which TCD parameters were measured within 48 hours from successful MT (Thrombolysis in Cerebral Infarction 2b–3) of anterior circulation. Risk of bias assessment was performed using a standardized tool tailored for TCD studies. The standardized mean difference (Hedges’ g) with 95% CI and risk ratios (RRs) with 95% CI were calculated using random-effects models. The review was prospectively registered on PROSPERO (registration number CRD42024575381). Results: Eleven studies met inclusion criteria. No study had high risk of bias. MFV and MFV index were higher in patients with HT+ compared with HT- (Hedges' g = 0.42 and 0.54, p = 0.015 and 0.005, respectively). Patients with MFV index ≥1.3 showed a higher risk of all HT (RR = 2.01, 95% CI = 1.27–3.17, p = 0.003), symptomatic HT (RR, 4.68; 95% CI,1.49–14.65, p=0.008), and poor functional recovery at 90 days (RR, 1.66; 95% CI,1.32–2.08, p<0.001), respectively. There was no difference in mean PSV (p=0.1) and PI (p=0.3) among groups with and without HT. Conclusion: Our study highlights the prognostic value of TCD parameters, particularly MFV index, in predicting HT, symptomatic HT, and poor functional recovery after successful MT in the anterior circulation. Our findings were limited by low number of studies. Large-scale and multi-center studies are needed to confirm these findings and validate the MFV index as a reliable predictor to improve post-thrombectomy care.

Introduction: Embolic Stroke of Undetermined Source (ESUS) represents about 25% of ischemic strokes, with patent foramen ovale (PFO) involved in roughly 25% of those cases. Recent studies (REDUCE, CLOSE, RESPECT) indicate that PFO closure may benefit select patients. Accurate PFO diagnosis is crucial for treatment decisions but current methods, such as transcranial Doppler (TCD) with bubble study, transthoracic echocardiography with bubble study (TTE), transesophageal echocardiography (TEE), and cardiac computed tomography (CT), vary in accuracy. This study aims to assess the diagnostic performance of TCD compared to TTE, TEE, and cardiac CT, to determine the most reliable modality for detecting PFO in patients with ESUS. Methods: We conducted a retrospective analysis of ESUS patients aged 18 and older referred to our vascular lab between July 2023 and September 2024. Each patient underwent at least two PFO detection methods: TCD with bubble study, TTE with bubble study, TEE, and cardiac CT. PFO presence was confirmed if identified by at least two detection methods. Patients with extracardiac shunts were excluded. Sensitivity, specificity, and overall test performance were evaluated using the Area Under the Curve (AUC) of a Receiver Operating Characteristic (ROC) curve, with higher AUC values indicating better performance. Differences in AUCs were assessed using DeLong’s test. Statistical analysis was performed using Analyse-it for Microsoft Excel (version 2.30). Results: Of 187 enrolled patients, 63 (33.7%) had evidence of right-to-left shunt. The mean age of the cohort was 63 ± 18 years, with 51% being male. PFO was confirmed in 36 patients. Sensitivity was highest for TCD (93.1%), followed by TTE (87.1%), TEE (86.7%), and cardiac CT (42.9%). Specificity was highest for cardiac CT (87.5%), followed by TTE (84%), TCD (59.1%), and TEE (47.1%). The AUC was highest for TTE (AUC: 0.85, 95% CI: 0.76–0.95), followed by TCD (AUC: 0.75, 95% CI: 0.64–0.87), TEE (AUC: 0.66, 95% CI: 0.50–0.81), and cardiac CT (AUC: 0.65, 95% CI: 0.42–0.88). No statistically significant differences in diagnostic performance across pairwise comparisons were found (p > 0.05). Conclusion: TCD with bubble study is highly sensitive for screening right-to-left shunt, while cardiac CT is highly specific for detecting PFO in ESUS patients. Further studies with larger sample sizes are needed to confirm these findings and refine diagnostic strategies.

Background Transcranial Doppler (TCD) is a non-invasive, bedside tool that allows for real-time monitoring of the patient’s hemodynamic status following mechanical thrombectomy (MT). This systematic review and meta-analysis aims to evaluate the predictive value of TCD parameters following successful MT (Thrombolysis in Cerebral Infarction 2b–3). Methods In July 2024, we searched PubMed, Embase, and Scopus, to identify observational studies in which TCD parameters were measured within 48 hours of MT. Using random-effects models, we compared four TCD parameters (mean flow velocity (MFV), MFV index, pulsatility index (PI), and peak systolic velocity (PSV) among groups with vs without hemorrhagic transformation (HT) and favorable vs poor functional recovery (modified Rankin Scale 0–2 vs 3–6). Results Eleven studies comprising 1432 patients (59% male; mean age range: 63–73 years) were included. The MFV and MFV index were higher in patients with HT (Hedges' g=0.42 and 0.54, P=0.015 and 0.005, respectively). Patients with MFV index ≥1.3 showed a higher risk of all HT (RR 1.97; 95% confidence interval (CI) 1.28 to 3.03, P=0.002), symptomatic HT (RR 4.68; 95% CI 1.49 to 14.65, P=0.008), and poor functional status at 90 days (RR 1.65; 95% CI 1.27 to 2.14, P=0.029), respectively. There was no difference in mean PSV (P=0.1) and PI (P=0.3) among groups with and without HT. Conclusion This study underscores the prognostic value of the MFV index in predicting HT, symptomatic HT, and poor functional recovery after successful MT in the anterior circulation. Large-scale, multi-center studies are necessary to confirm these findings and to validate the MFV index as a reliable predictor for improving post-thrombectomy care.

AbstractBackgroundCervical artery dissection (CAD) is a common cause of ischemic stroke in young adults. Local blood clot formation and distal emboli are the key mechanisms for the development of stroke in patients with CAD. Microemboli distal to the dissection point can be detected as high‐intensity transient signals (HITS) using transcranial Doppler (TCD). Despite this unique capability, TCD is used inconsistently in the management of CAD. In this international survey, we aim to explore the frequency and potential barriers to TCD use in CAD.MethodThis study was an international electronic survey, based on the Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP‐CAD) study, aiming at evaluating the use of TCD in diagnosing and managing CAD patients. A comprehensive questionnaire was developed to gather insights into the current practices, perceptions, and potential barriers to the effective use of TCD in participating centers. The collected data was then analyzed.ResultsFifty‐eight medical centers with advanced stroke care capabilities from Europe and United States participated in this study. Half (29 out of 58) of the sites routinely perform TCD on CAD patients, particularly in the presence of carotid or vertebral artery stenosis, complete carotid occlusion, and early neurologic deterioration. The primary reason for participating institutions not performing TCD was because its results would not change their practice. The protocol for TCD monitoring and managing HITS‐positive CAD patients varied among centers but transitioning from antiplatelet to anticoagulant was the most common practice in this patient population.ConclusionHalf of the stroke centers in our survey routinely perform TCD monitoring for CAD patients. The detection of HITS in CAD patients is a warning sign for providers, which may prompt a change in secondary stroke prevention management. However, a standard protocol for performing TCD in CAD and treatment recommendations for HITS‐positive CAD are not currently available, which warrants further research.

Background: Whether thrombolysis improves outcomes in non-arteritic central retinal artery occlusion (naCRAO) is uncertain. We aimed to evaluate the rate of visual recovery after intra-venous thrombolysis (IVT) or intra-arterial thrombolysis (IAT) administration of tissue plasminogen activator (tPA) or urokinase among patients with naCRAO and explore the parameters affecting the final visual acuity (VA). Aim: We systematically searched six databases. Logarithm of the minimum angle of resolution (logMAR) and VA of ⩾20/100 were used to quantify visual recovery. To explore the role of other factors on visual recovery, we defined two models for studies with aggregated data (designs 1 and 2) and 16 models for individual participant data (IPD, models 1–16). Summary of Review: We included data from 771 patients out of 72 publications in nine languages. Visual improvement for ⩾0.3 logMAR was reported in 74.3% of patients who received IVT-tPA within 4.5 h (CI: 60.9–86.0%; unadjusted rate: 73.2%) and 60.0% of those who received IAT-tPA within 24 h (CI: 49.1–70.5%; unadjusted rate: 59.6%). VA of ⩾20/100 was observed among 39.0% of patients after IVT-tPA within 4.5 h and 21.9% of those with IAT-tPA within 24 h. IPD models highlighted the association between improved visual outcomes and VA at presentation, at least 2 weeks follow-up before reporting the final VA, antiplatelet therapy, and shorter symptom onset to thrombolysis window. Conclusion: Early thrombolytic therapy with tPA is associated with enhanced visual recovery in naCRAO. Future studies should refine the optimum time window for thrombolysis in naCRAO.