Association of masseter area and radiodensity with three-month survival after proximal anterior circulation occlusion.

BACKGROUND: Masseter area (MA), a surrogate for sarcopenia, appears to be useful when estimating postoperative survival, but there is lack of consensus regarding the potential predictive value of sarcopenia in acute ischemic stroke (AIS) patients. We hypothesized that MA and density (MD) evaluated from pre-interventional CT angiography scans predict postinterventional survival in patients undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: 312 patients treated with MT for acute occlusions of the internal carotid artery (ICA) or the M1 segment of the middle cerebral artery (M1-MCA) between 2013 and 2018. Median follow-up was 27.4 months (range 0-70.4). Binary logistic (alive at 3 months, OR <1) and Cox regression analyses were used to study the effect of MA and MD averages (MAavg and MDavg) on survival. RESULTS: In Kaplan-Meier analysis, there was a significant inverse relationship with both MDavg and MAavg and mortality (MDavg P<0.001, MAavg P=0.002). Long-term mortality was 19.6% (n=61) and 3-month mortality 12.2% (n=38). In multivariable logistic regression analysis at 3 months, per 1-SD increase MDavg (OR 0.61, 95% CI 0.41 to 0.92, P=0.018:) and MAavg (OR 0.57, 95% CI 0.35 to 0.91, P=0.019) were the independent predictors associated with lower mortality. In Cox regression analysis, MDavg and MAavg were not associated with long-term survival. CONCLUSIONS: In acute ischemic stroke patients, MDavg and MAavg are independent predictors of 3-month survival after MT of the ICA or M1-MCA. A 1-SD increase in MDavg and MAavg was associated with a 39%-43% decrease in the probability of death during the first 3 months after MT.

Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients.

BACKGROUND: In patients suffering from acute ischemic stroke from large vessel occlusion (LVO), mechanical thrombectomy (MT) often leads to successful reperfusion. Only approximately half of these patients have a favorable clinical outcome. Our aim was to determine the prognostic factors associated with poor clinical outcome following complete reperfusion. METHODS: Patients treated with MT for LVO from a prospective single-center stroke registry between July 2015 and April 2019 were screened. Complete reperfusion was defined as Thrombolysis in Cerebral Infarction (TICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as 'poor outcome'. A logistic regression analysis was performed with poor outcome as a dependent variable, and baseline clinical data, comorbidities, stroke severity, collateral status, and treatment information as independent variables. RESULTS: 123 patients with complete reperfusion (TICI 3) were included in this study. Poor clinical outcome was observed in 67 (54.5%) of these patients. Multivariable logistic regression analysis identified greater age (adjusted OR 1.10, 95% CI 1.04 to 1.17; p=0.001), higher admission National Institutes of Health Stroke Scale (NIHSS) (OR 1.14, 95% CI 1.02 to 1.28; p=0.024), and lower Alberta Stroke Program Early CT Score (ASPECTS) (OR 0.6, 95% CI 0.4 to 0.84; p=0.007) as independent predictors of poor outcome. Poor outcome was independent of collateral score. CONCLUSION: Poor clinical outcome is observed in a large proportion of acute ischemic stroke patients treated with MT, despite complete reperfusion. In this study, futile recanalization was shown to occur independently of collateral status, but was associated with increasing age and stroke severity.

Relationship of white matter lesion severity with early and late outcomes after mechanical thrombectomy for large vessel stroke.

BACKGROUND: White matter lesions (WML) are associated with poor outcome after mechanical thrombectomy (MT) for large vessel stroke; the reasons are uncertain. To elucidate this issue we sought to determine the association of WML with multiple early and late outcome measures after MT. METHODS: We retrospectively analyzed 181 MT patients prospectively included in our local stroke registry (January 2012 to November 2016). Using multiple regression modeling, we assessed whether WML was independently associated with early outcomes (successful recanalization, degree of National Institutes of Health Stroke Scale (NIHSS) improvement, hemorrhagic transformation, duration of hospitalization) as well as an unfavorable 90-day modified Rankin Scale score (mRS) (≥3) and 90-day survival. Explorative analyses examined the association with the 90-day home-time and 90-day risk for hospital readmission. RESULTS: WML were not significantly associated with early outcome measure (P>0.05, each). Patients with moderate-to-severe WML more often had an unfavorable mRS (OR 2.93, 95% CI 1.04 to 8.33) and risk of death (HR 1.98, 95% CI 1.03 to 3.84) after adjustment for pertinent confounders. Patients with moderate-to-severe WML had a significantly shorter home-time (19±32 vs 47±38 days, P<0.001) and Kaplan-Meier analyses indicated a significantly greater risk for hospital readmission within 90 days (log rank P=0.045), with the most frequent reasons being recurrent stroke and transient ischemic attack. CONCLUSION: Our analyses suggest that poor outcomes among patients with moderate-to-severe WML were related to factors unrelated to procedural success and risk. WML should not be used to render treatment decisions in otherwise eligible patients. Aggressive monitoring of medical complications after MT could represent a viable strategy to improve outcome in affected patients.

Implications of the use of mechanical thrombectomy on outcome in large vessel occlusion following the 2015 landmark trials.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) was demonstrated in five landmark trials published in2015.Mechanical thrombectomy is now standard of care for acute ischemic stroke and has been growing in popularity after publication of landmark trials. OBJECTIVE: To analyze outcomes and trends of the use of MT and intravenous thrombolysis (IVT) in patients with acute ischemic stroke in US hospitals before and after publication of these trials. METHODS: Patients discharged with a diagnosis of ischemic stroke between 2012 to 2017 were diagnosed using ICD codes from the National Inpatient Sample. Thereafter, patients given acute stroke treatment were identified using the corresponding procedure codes for IVT and MT. The primary clinical outcomes of in-hospital mortality and disability were then compared between two time periods: 2012-2014 (pre-landmark trials) and 2015-2017 (post-landmark trials). Binary logistic regression and Χ2 tests were used for statistical analysis. RESULTS: A total of 57 675 patients (median age 68.9 years (range 18-90), 50.1% female) were identified with acute procedures. Of these patients, 57.6% were from the post-landmark trials time period. Despite an increased number of cases, the rate of IVT decreased from 84.3% to 75.9% and the rate of IVT+MT decreased from 7.1% to 6.3%. After publication of the pivotal trials in 2015, the rates of MT increased from 8.7% to 17.8%. Significant reductions of in-hospital mortality (7.1% vs 8.7%, p<0.001) and disability (64% vs 66.2%, p<0.001) were noted. CONCLUSION: The analysis showed a significant increase in the proportion of patients receiving MT after 2015. This has translated into reduction of in-hospital mortality and improvement in disability.

Repeated mechanical thrombectomy in short-term large vessel occlusion recurrence: multicenter study and systematic review of the literature.

BACKGROUND: Data on the frequency and outcome of repeated mechanical thrombectomy (MT) in patients with short-term re-occlusion of intracranial vessels is limited. Addressing this subject, we report our multicenter experience with a systematic review of the literature. METHODS: A retrospective analysis was conducted of consecutive acute stroke patients treated with MT repeatedly within 30 days at 10 tertiary care centers between January 2007 and January 2020. Baseline demographics, etiology of stroke, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at 90 days were noted. Additionally, a systematic review of reports with repeated MT due to large vessel occlusion (LVO) recurrence was performed. RESULTS: We identified 30 out of 7844 (0.4%) patients who received two thrombectomy procedures within 30 days due to recurrent LVO. Through systematic review, three publications of 28 participants met the criteria for inclusion. Combined, a total of 58 participants were analyzed: cardioembolic events were the most common etiology for the first (65.5%) and second LVO (60.3%), respectively. Median baseline NIHSS (National Institutes of Health Stroke Scale) was 13 (IQR 8-16) before the first MT and 15 (IQR 11-19) before the second MT (p=0.031). Successful reperfusion was achieved in 91.4% after the first MT and in 86.2% patients after the second MT (p=0.377). The rate of functional independence (mRS 0-2) was 46% at 90 days after the second procedure. CONCLUSION: Repeated MT in short-term recurrent LVO is a rarity but appears to be safe and effective. The second thrombectomy should be pursued with the same extensive effort as the first procedure as these patients may achieve similar good outcomes.

Implications of achieving TICI 2b vs TICI 3 reperfusion in patients with ischemic stroke: a cost-effectiveness analysis.

BACKGROUND: The benefit of endovascular thrombectomy (EVT) in stroke patients with large-vessel occlusion (LVO) depends on the degree of recanalization achieved. We aimed to determine the health outcomes and cost implications of achieving TICI 2b vs TICI 3 reperfusion in acute stroke patients with LVO. METHODS: A decision-analytic study was performed with Markov modeling to estimate the lifetime quality-adjusted life years (QALY) of EVT-treated patients, and costs based on the degree of reperfusion achieved. The study was performed with a societal perspective in the United States' setting. The base case calculations were performed in three age groups: 55-, 65-, and 75-year-old patients. RESULTS: Within 90 days, achieving TICI 3 resulted in a cost saving of $3676 per patient and health benefit of 11 days in perfect health as compared with TICI 2b. In the long term, for the three age groups, achieving TICI 3 resulted in cost savings of $46,498, $25,832, and $15 719 respectively, and health benefits of 2.14 QALYs, 1.71 QALYs, and 1.23 QALYs. Every 1% increase in TICI 3 in 55-year-old patients nationwide resulted in a cost saving of $3.4 million and a health benefit of 156 QALYs. Among 65-year-old patients, the corresponding cost savings and health benefit were $1.9 million and 125 QALYs. CONCLUSION: There are substantial cost and health implications in achieving complete vs incomplete reperfusion after EVT. Our study provides a framework to assess the cost-benefit analysis of emerging diagnostic and therapeutic techniques that might improve patient selection, and increase the chances of achieving complete reperfusion.

Intravenous thrombolysis pretreatment and other predictors of infarct in a new previously unaffected territory (INT) in ELVO strokes treated with mechanical thrombectomy.

INTRODUCTION: One uncommon complication of mechanical thrombectomy (MT) is an infarct in a new previously unaffected territory (infarct in new territory (INT)). OBJECTIVE: To evaluate the predictors of INT with special focus on intravenous thrombolysis(IVT)pretreatmentbefore MT. METHODS: Consecutive patients with emergent large vessel occlusion (ELVO) treated with MT during a 5-year period were evaluated. INT was defined using standardized methodology proposed by ESCAPE investigators. The predictors of INT and its impact on outcomes were investigated. RESULTS: A total of 419 consecutive patients with ELVO received MT (mean age 64±15 years, 50% men, median baseline National Institutes of Health Stroke Scale score 16 points (IQR 11-20), 69% pretreated with IVT). The incidence of INT was lower in patients treated with combination therapy (IVTandMT) than in patients treated with MT alone, respectively (10% vs 20%; p=0.011). The INT group had more patients with posterior circulation occlusions than the group without INT (28% vs 10%, respectively; p<0.001). The rates of 3-month functional independence were lower in patients with INT (30% vs 50%; p=0.007). IVT pretreatment was not independently related to INT (OR=0.75; 95% CI 0.32 to 1.76), and INT did not emerge as an independent predictor of 3-month functional independence (OR=0.69; 95% CI 0.29 to 1.62) on multivariable logistic regression models. Location of posterior circulation occlusion was independently associated with a higher odds of INT (OR=3.33; 95% CI 1.43 to 7.69; p=0.005). CONCLUSIONS: IVT pretreatment is not independently associated with a lower likelihood of INT in patients with ELVO treated with MT. Patients with ELVO with posterior circulation occlusion are more likely to have INT after MT.

Association between age and outcomes following thrombectomy for anterior circulation emergent large vessel occlusion is determined by degree of recanalisation.

BACKGROUND: Older patients undergoing thrombectomy for emergent large vessel occlusion have worse outcomes. However, complete or near-complete reperfusion (modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2 c/3) is associated with improved outcomes compared with partial recanalisation (mTICI 2b). OBJECTIVE: To examine the relationship between outcomes and age separately for the mTICI 2c/3, 2b and 0-2a groups in patients undergoing thrombectomy for anterior circulation emergent large vessel occlusion. METHODS: Retrospective review of 157 consecutive patients undergoing thrombectomy at a single centre with an occlusion of the internal carotid artery (ICA), M1 or proximal M2 segments of the middle cerebral artery (MCA). Angiograms were graded in a blinded fashion. Patients were divided into three groups: mTICI 0-2a, mTICI 2b, and mTICI 2c/3. Demographics and workflow parameters were compared. Outcomes at 90 days were compared as a function of age, using both the conventional modified Rankin scale (mRs) and utility weighted mRs (UWmRs). RESULTS: There were 72, 61 and 24 patients in the mTICI 2c/3, 2b and 0-2a groups, respectively. Outcomes were significantly worse with increasing age for the mTICI 2b group, but not for the mTICI 0-2a and 2c/3 groups (P=0.0002). With increasing age, outcomes of the mTICI 2b group approached those of the mTICI 0-2a group. However, outcomes of the mTICI 2c/3 groups were similar for all ages. This association was present for both the original mRs and UWmRs. CONCLUSION: Increasing age was associated with worse outcomes for those with partial (mTICI 2b) recanalisation, not in patients with complete (mTICI 2c/3) recanalisation.

Leukoaraiosis severity and outcomes after mechanical thrombectomy with stent-retriever devices in acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis severity is associated with outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices. METHODS: In this retrospective multicenter study, we evaluated 251 acute stroke patients (pretreatment National Institutes of Health Stroke Scale score ≥8) treated with stent-retriever devices. Leukoaraiosis severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of good functional outcome, defined as a modified Rankin Scale of 0-2 at 90 days. RESULTS: Significantly fewer patients in the severe LA group than in the absent-to-moderate LA group achieved a good functional outcome (18.4% vs 50.2%, P<0.001). In multivariable analysis, severe leukoaraiosis was a significant negative predictor of good functional outcome at 90 days (OR, 0.27; 95% CI 0.10-0.77; P=0.014). CONCLUSIONS: The severity of leukoaraiosis is independently associated with 90-day functional outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices.

Elevated mean platelet volume is associated with poor outcome after mechanical thrombectomy.

BACKGROUND: Elevated mean platelet volume (MPV), indicating higher platelet activity, could be a predictor of prognosis in patients with acute ischemic stroke receiving medical therapy. OBJECTIVE: To investigate the relationship between MPV and functional outcome in patients with acute anterior circulation stroke 3 months after undergoing mechanical thrombectomy (MT). METHODS: A total of 153 consecutive patients with acute stroke following MT, in two separate stroke centers, were enrolled between May 2013 and March 2016. MPV was measured on admission. Subjects were divided into two groups according to average MPV level. Univariate and multivariate analyses were performed. MPV was also incorporated into the Houston IA Therapy (HIAT) score, which was developed as a scoring system to predict poor prognosis, and the prediction capability was compared with the HIAT score alone. RESULTS: The average MPV was 10.4 fL. Patients with high MPV had a significantly lower rate of functional independence (28.9% vs 57.1%, p=0.000). After multivariable analysis, elevated MPV remained an independent predictor of unfavorable outcome (OR=3.93, 95% CI 1.73 to 8.94, p=0.001). When the MPV cut-off value was set at 10.4 fL using the receiver operating characteristic (ROC) analysis, MPV ≥10.4 fL predicted unfavorable outcome with 62.1% sensitivity and 66.7% specificity, respectively. Addition of MPV to the HIAT score did not improve predictive power compared with the HIAT score system alone by a comparison of the areas under the two ROC curves (0.70 vs 0.62, p=0.174). CONCLUSIONS: Elevated MPV is an independent predictor of poor outcome in patients with acute anterior circulation stroke undergoing MT at 3 months.

New horizons for focused ultrasound (FUS) - therapeutic applications in neurodegenerative diseases.

Access to the CNS and delivery of therapeutics across the blood-brain barrier remains a challenge for most treatments of major neurological diseases such as AD or PD. Focused ultrasound represents a potential approach for overcoming these barriers to treating AD and PD and perhaps other neurological diseases. Ultrasound (US) is best known for its imaging capabilities of organs in the periphery, but various arrangements of the transducers producing the acoustic signal allow the energy to be precisely focused (F) within the skull. Using FUS in combination with MRI and contrast agents further enhances accuracy by providing clear information on location. Varying the acoustic power allows FUS to be used in applications ranging from imaging, stimulation of brain circuits, to ablation of tissue. In several transgenic mouse models of AD, the use of FUS with microbubbles reduces plaque load and improves cognition and suggests the need to investigate this technology for plaque removal in AD. In PD, FUS is being explored as a way to non-invasively ablate the brain areas responsible for the tremor and dyskinesia associated with the disease, but has yet to be utilized for non-invasive delivery of putative therapeutics. The FUS approach also greatly increases the range of possible CNS therapeutics as it overcomes the issues of BBB penetration. In this review we discuss how the characteristics and various applications of FUS may advance the therapeutics available for treating or preventing neurodegenerative disorders with an emphasis on treating AD and PD.

Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis.

BACKGROUND: No randomized trial has investigated the effect of mechanical thrombectomy (MT) alone in patients with acute stroke. There are conflicting results as to whether prior intravenous thrombolysis (IVT) facilitates subsequent MT, and data in patients treated with MT alone owing to contraindications to IVT are limited. OBJECTIVE: To compare consecutive patients treated with MT alone or with preceding IVT in a large tertiary neurointerventional center, with special emphasis on contraindications to IVT. METHODS: Retrospective analysis of 283 consecutive patients with acute ischemic stroke treated with MT in a tertiary neurovascular center over 14 months. Data on characteristics of periprocedural times, recanalization rate, complications, and long-term functional outcome were collected prospectively. RESULTS: Information on prior IVT and functional outcome was available in 250 patients. Mean (SD) follow-up period was 5.7 (5.1) months and 105 (42%) patients received both IVT and MT. No significant differences were found in successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) 2b/3, 73.8% vs 73.1, p=0.952), complication rates, and long-term favorable outcome (modified Rankin Scale 0-2, 35.2% vs 40%, p=0.444) between patients receiving MT plus IVT and those receiving MT alone. A favorable outcome in patients directly treated with MT alone who were eligible for IVT was achieved in 48.2%. Thrombectomy was safe and resulted in a favorable outcome in 32% of patients with absolute contraindications to IVT. CONCLUSIONS: Preceding use of IVT was not an independent predictor of favorable outcome in patients with acute stroke treated with MT and complication rates did not differ whether or not IVT was used. MT is safe and achieved a favorable outcome in one-third of patients with stroke ineligible for IVT.

Lenticulostriate infarctions after successful mechanical thrombectomy in middle cerebral artery occlusion.

BACKGROUND: In stroke due to middle cerebral artery (MCA) occlusion, collaterals may sustain tissue in the peripheral MCA territory, extending the time window for recanalizing therapies. However, MCA occlusions often block some or all of the 'lenticulostriate' (LS) arteries originating from the M1 segment, eliminating blood flow to dependent territories in the striatum, which have no collateral supply. This study examines whether mechanical thrombectomy (MTE) can avert imminent striatal infarction in patients with acute MCA occlusion. METHODS: 279 patients with isolated MCA occlusion subjected to MTE were included. Actual LS occlusions and infarctions were assigned to predefined 'LS occlusion' and 'LS infarct' patterns derived from known LS vascular anatomy. The predictive performance of LS occlusion patterns regarding ensuing infarction in striatal subterritories was assessed by standard statistical measures. RESULTS: LS occlusion patterns predicted infarction in associated striatal subterritories with a positive predictive value (PPV) of 91% and a negative predictive value of 81%. In 15 of the 22 patients who did not develop the predicted striatal infarctions, reassessment of angiographies revealed LS vascular supply variants that explained these 'false positive' LS occlusion patterns, raising the PPV to 96%. Symptom onset to recanalization times were relatively short, but this alone could not account for the false positive LS occlusion patterns in the remaining seven of these patients. CONCLUSIONS: With currently achievable symptom onset to recanalization times, striatal infarctions are determined by MCA occlusion sites and individual vascular anatomy, and cannot normally be averted by MTE, but there are exceptions. Further study of such exceptional cases may yield important insights into the determinants of infarct growth in the hyperacute phase of infarct evolution.

Patterns in the Management of Acute Limb Ischemia: A VESS Survey.

BACKGROUND: Treatment strategies for acute limb ischemia (ALI) are abundant with few established guidelines. We sought to determine nationwide ALI treatment patterns in the modern era. METHODS: Anonymous electronic surveys examining the management of ALI involving native vessel and bypass occlusion were sent to all members of the Vascular and Endovascular Surgery Society (n = 738). Treatment options included catheter-directed lysis (CDL) or pharmacomechanical (PMT) thrombolysis and open surgery. CDL management strategies were evaluated for lytic and heparin dosing, fibrinogen monitoring, and treatment duration. Influence of Rutherford category (RC), time from training, practice type, hospital size, region, and protocol use was assessed. Data were analyzed by univariate contingency tables and multinomial regression analysis. RESULTS: A total of 117 (response rate of 16%) surveys were completed. The most common management strategy RC 2a ischemia in all conduit occlusions was endovascular (prosthetic graft, 96 [82%] respondents; vein graft 96 [82%] respondents; native artery occlusion 79 [68%] respondents), while those with RC 3 ischemia were more commonly treated with open techniques (prosthetic graft, 96 [83%]; vein graft 94 [81%]; native artery occlusion 94 [80%]). Of those respondents using endovascular therapy, CDL was most commonly used in RC 2a patients, while PMT was most commonly used in RC 3 patients. Multivariate analysis identified prosthetic and vein graft occlusion were more likely to be treated via endovascular approach (odds ratio, 2.45 and 2.78, respectively; P < 0.001), while those with RC 2b (odds ratio, 0.19; P < 0.001), RC 3 (odds ratio, 0.01; P < 0.001), or in centers without a hybrid operating room (odds ratio, 0.49; P = 0.017) were more likely to be treated by open approach. Tissue plasminogen activator (TPA) dosing during catheter directed therapy was usually 1 mg/hr (77%) with variable concentrations and duration of the initial treatment of 8-24 hr (78%). Most respondents indicated having developed their own protocols and patterns of treatment varied but were influenced by training and practice environment variables. CONCLUSIONS: Management strategies vary widely in ALI. Some effects of provider training and individual protocol development were observed, and TPA protocols were influenced by increased institutional responsibility for thrombolysis. Further efforts are needed to develop consensus guidelines for ALI management.

Current status of venous thromboembolism prophylaxis.

Postoperative venous thromboembolism (VTE) represents a serious and potentially fatal complication that affects 40% to 60% of patients undergoing major orthopedic surgery and not receiving antithrombotic prophylaxis. Several prophylactic modalities, including pharmacological agents such as oral vitamin K antagonists (VKA) and low molecular weight heparins (LMWH), have been shown to be effective and safe for most patients at high risk for VTE. However, some patients undergoing cancer or major orthopedic surgery remain at some residual VTE risk despite the use of these methods. Approaches to improve the results of prophylaxis include optimizing the timing and duration of pharmacological prophylaxis, combining mechanical methods with anticoagulants, and the development of new antithrombotics.