Clinical impact of the first pass effect on clinical outcomes in patients with near or complete recanalization during mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND AND PURPOSE: The first pass effect has been reported as a mechanical thrombectomy (MT) success metric in patients with large vessel occlusive stroke. We aimed to compare the clinical and neuroimagign outcomes of patients who had favorable recanalization (mTICI 2c or mTICI 3) achieved in one pass versus those requiring multiple passes. METHODS: In this "real-world" multicenter study, patients with mTICI 2c or 3 recanalization were identified from three prospectively collected stroke databases from January 2016 to December 2019. Clinical outcomes were a favorable functional outcome at 90 days (modified Rankin Scale score 0-2), and the rate of symptomatic intracranial hemorrhage (ICH) any ICH, and 90-day mortality. RESULTS: Favorable recanalization was achieved in 390/664 (59%) of consecutive patients who underwent MT (age 71.2 ± 13.2 years, 188 [48.2%] women). This was achieved after a single thrombectomy pass (n = 290) or multiple thrombectomy passes (n = 100). The rate of favorable clinical outcome was higher (41% vs. 28 %, p = .02) in the first pass group with a continued trend on multivariate analysis that did not reaching statistical significance (OR 1.68 95% confidence interval [CI] 1.0-2.95, p = .07). Similarly, the odds of any ICH were significantly lower (OR 0.56 CI 0.32-0.97, p = .03). A similar trend of favorable clinical outcomes was noticed on subgroup analysis of patients with M1 occlusion (OR 1.81 CI 1.01-3.61, p = .08). CONCLUSION: The first-pass reperfusion was associated with a trend toward favorable clinical outcome and lower rates of ICH. These data suggest that the first-pass effect should be the mechanical thrombectomy procedure goal.

Fixed Dose IV rt-PA and Clinical Outcome in Ischemic Stroke Patients With Body Weight >100 kg: Pooled Data From 3 Randomized Clinical Trials.

BACKGROUND AND PURPOSE: The ASA/AHA guidelines recommend a fixed dose of 90 mg of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) for acute stroke patients weighing more than 100 kg. We aimed to determine if body weight >100 kg (and receiving <0.9 mg/kg dose) independently influence patient clinical outcomes following IV rt-PA treatment. METHODS: We pooled data from IV rt-PA treatment arms from 3 randomized controlled clinical trials; NINDS IV rt-PA study, Interventional Management of Stroke 3 and ALIAS (part 1 and 2). Baseline characteristic, hospital course and 90-day mRS were compared between patients >100 kg and those ≤100 kg body weight. Multivariate logistic regression model was used to identify the independent effect of >100 kg body weight on favorable 90-day outcome (defined as mRS 0-2), the rate of symptomatic intracranial hemorrhage, and poor 90-day outcome (mRS 4-6). RESULTS: Among 873 patients treated with IV rt-PA, a total of 105 (12%) subjects had body weight >100 kg. Compared with patients having ≤100 kg body weight, the rate of favorable outcome at 90 days was not significantly different among patients with >100 kg body weight (OR: 0.99; 95% CI: 0.91-1.01; p=0.91) , after adjusting for potential confounders. The ordinal analysis did not show any significant shift in the distribution of 90-day mRS score in patients with >100 kg body weight (OR, 0.93; 95% CI, 0.64-1.37; P = 0.74) CONCLUSIONS: There was no reduction in the rate of favorable outcome in patients with acute ischemic stroke with body weight >100 kg who received <0.9 mg/kg dose of IV rt-PA. Our results support the current recommendations in the ASA/AHA guidelines.

Inpatient versus Outpatient Management of TIA or Minor Stroke: Clinical Outcome.

BACKGROUND: The management of patients with acute transient ischemic attack (TIA) or minor stroke is highly variable. Whether hospitalization of such patients significantly improves short-term clinical outcome is unknown. We assessed the short-term clinical outcome associated with inpatient versus outpatient management of patients with TIA or minor stroke. METHODS: We evaluated a consecutive series of patients with acute TIA or minor ischemic stroke (NIH Stroke Scale score ≤ 3) presenting to a single emergency department (ED). We randomized patients to either hospital-based or outpatient-based management. All patients underwent interview and examination 7-10 days following the index event. RESULTS: This study included 100 patients, 41 with TIA and 59 with minor stroke. Nineteen (46%) of the TIA patients and 29 (49%) of the minor stroke patients randomized to hospital management, and the remaining 22 TIA patients and 30 minor stroke patients randomized to outpatient-based management. In the patients with a minor stroke, neurologic worsening occurred in 6 out of 29 (21%) in the inpatient arm compared with 3 out of 30 (10%) in the outpatient arm (p = 0.3). In none of these cases was acute interventional therapy or need for urgent admission considered medically appropriate. In the patients with a TIA, recurrence of a TIA occurred in 2 out of 19 (11%) in the inpatient arm compared with 2 out of 22 (9%) in the outpatient arm (p = 1). None of the patients with a TIA randomized to the inpatient arm experienced a stroke compared with 1 out of 22 in the outpatient arm (p = 1). There were no deaths in either group. CONCLUSION: Routine hospitalization of all patients with TIA or minor ischemic stroke may not positively affect short-term clinical outcome.

Numerous Fusiform and Saccular Cerebral Aneurysms in Central Nervous System Lupus Presenting with Ischemic Stroke.

Central nervous system (CNS) involvement occurs in up to 50% of patients with systemic lupus erythematosus (SLE). Cerebral aneurysm formation is a rare complication of CNS lupus. The majority of these patients present with subarachnoid hemorrhage. We report a patient with an active SLE flare who presented with a recurrent ischemic stroke and was found to have numerous unruptured fusiform and saccular aneurysms in multiple vascular territories. He was treated with high-dose steroid and rituximab along with aspirin and blood pressure control for stroke prevention.

Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke: The NHLBI Exome Sequence Project.

IMPORTANCE: Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk. OBJECTIVE: To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome. DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013. MAIN OUTCOMES AND MEASURES: Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis). RESULTS: We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 × 10(-8)) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 × 10(-7)) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke). CONCLUSIONS AND RELEVANCE: Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy.

Brainstem vascular stroke anatomy.

Brainstem infarcts comprise approximately 10% of all first ischemic brain strokes. The extrinsic vascular supply to the stem is complex. The intrinsic vascularization of the stem may be conceptualized in terms of four relatively constant and distinct vascular territories designated anteromedial, anterolateral, lateral, and dorsal (or dorsolateral). The anatomic structures found within each intrinsic territory determine the symptomatology associated with infarction of that territory. This territorial anatomy permits the knowledgeable physician to plan an MR imaging examination tailored to the patient's history and to predict the patient's neurologic deficits from the MR imaging findings.

Thrombolytic treatment of acute cerebral infarction.

Stroke is a common cause of death and disability throughout the world. Acute neurologic deficits due to ischemic injury deserve rapid recognition and diagnosis in order to provide effective therapy. Intravenous tissue plasminogen activator (t-PA) provided to carefully selected patients that can be treated within 3 hours of stroke onset results in improved outcome in these patients. Intra-arterial administration of t-PA within a 6-hour window is performed at several academic centers in patients with middle cerebral and other intracranial artery occlusions based on results of one randomized clinical trial and numerous case reports. Although acute therapy of ischemic stroke has received much attention since the approval of intravenous t-PA, only a small percentage of individuals suffering a stroke actually receive t-PA. This article will review the optimal management of the acute stroke patient and discuss thrombolytic clinical trials that have been completed as well as those that are in progress.

Antithrombotic trials in acute ischaemic stroke: a selective review.

Stroke is a common cause of morbidity and mortality throughout the US and the world. Given the highly disabling nature of this disease, it is important to provide acute therapy when indicated to improve individual outcomes. Recombinant tissue plasminogen activator (rt-PA) is, at present, the only approved drug for the treatment of acute strokes due to cerebral ischaemia. It can be given intravenously within a 3-h window of the onset of neurological deficits. Intra-arterial administration of rt-PA within a 6-h window is performed at several academic centres in patients with middle cerebral and other intracranial artery occlusions based on results of a randomised clinical trial. Other thrombolytic agents are being studied in randomised trials. Although acute therapy of ischaemic stroke has received much attention since the approval of rt-PA, only a small percentage of individuals actually receive rt-PA. This article will review the main thrombolytic agents and the trials performed thus far, as well as examine some important ongoing trials. How administration of acute thrombolytic therapy may evolve in the future will also be addressed.