Long-term age-dependent behavioral changes following a single episode of fetal N-methyl-D-Aspartate (NMDA) receptor blockade

BACKGROUND: Administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine during the perinatal period can produce a variety of behavioral and neuroanatomical changes. Our laboratory has reported reliable changes in learning and memory following a single dose of ketamine administered late in gestation. However, the nature of the drug-induced changes depends on the point during embryonic development when ketamine is administered. Embryonic day 18 (E18) rat fetuses pre-treated with ketamine (100 mg/kg, i.p. through the maternal circulation) and taught a conditioned taste aversion (CTA) learn and remember the CTA, whereas E19 fetuses do not. The current study sought to determine if long-term behavioral effects could be detected in animals that received ketamine or a saline control injection on either E18 or E19. Rat behavior was evaluated on two different measures: spontaneous locomotion and water maze learning. Measurements were collected during 2 periods: Juvenile test period [pre-pubertal locomotor test: Postnatal Day 11 (P11); pre-pubertal water maze test: P18] or Young-adult test period [post-pubertal locomotor test: P60; post-pubertal water maze test: P81]. RESULTS: Water maze performance of ketamine-treated rats was similar to that of controls when tested on P18. Likewise, the age of the animal at the time of ketamine/saline treatment did not influence learning of the maze. However, the young-adult water maze test (P81) revealed reliable benefits of prenatal ketamine exposure – especially during the initial re-training trial. On the first trial of the young adult test, rats treated with ketamine on E18 reached the hidden platform faster than any other group – including rats treated with ketamine on E19. Swim speeds of experimental and control rats were not significantly different. Spontaneous horizontal locomotion measured during juvenile testing indicated that ketamine-treated rats were less active than controls. However, later in development, rats treated with ketamine on E18 were more active than rats that received the drug on E19. CONCLUSION: These data suggest that both the day in fetal development when ketamine is administered and the timing of post-natal behavioral testing interact to influence behavioral outcomes. The data also indicate that the paradoxical age-dependent effects of early ketamine treatment on learning, previously described in fetuses and neonates, may also be detected later in young adult rats

Abstract WP1: Thrombectomy Outcomes in Acute Ischemic Stroke due to Middle Cerebral Artery M2 Occlusion with Stent-Retriever, Aspiration, MERCI: Multi-Center Experience

Introduction: Recent trials demonstrated that mechanical thrombectomy improve functional outcome in anterior circulation acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) of the middle cerebral artery (MCA) M1 segment. However, such data regarding AIS due to MCA M2 segment ELVO is limited. Analysis of the STAR, SWIFT, and SWIFT-PRIME trials found thrombectomy in MCA M2 occlusion to be feasible in achieving successful reperfusion. The most optimal technique and/or device used for such reperfusion is not clearly defined. We aim to compare the outcome for the contemporary techniques and devices used for thrombectomy of AIS patients due to MCA M2 ELVO. Methods: A retrospective review of AIS patients with MCA M2 ELVO receiving thrombectomy from three tertiary care academic medical centers was conducted. Thrombectomy technique and thrombectomy device utilized were recorded. Outcomes were successful angiographic reperfusion (TICI ≥2b), favorable modified Rankin Scale (mRS≤2) at discharge and at 90 days, and rate of symptomatic intracerebral hemorrhage (sICH). Results: From October 1999 through June 2016, 253 AIS patients underwent thrombectomy for MCA M2 ELVO. Thrombectomy methods utilized were Stent-retriever (n=118), Aspiration only [manual or Penumbra device] (n=83), and MERCI retriever (n=52). Table 1 shows rate of outcomes measured. There was no difference in baseline NIHSS or in stroke onset to groin puncture time. Stent-retriever group showed a significantly higher recanalization rate, lower sICH rate, and favorable 90-day mRS versus Aspiration group or MERCI group, respectively. No significant difference was seen in discharge mRS between the groups. Conclusions: Thrombectomy for AIS patients with MCA M2 ELVO with Stent-retriever appears to be feasible with a significantly higher rate of recanalization, lower sICH rate, and favorable 90-day mRS when compared to Aspiration and MERCI

Thrombectomy Outcomes in Acute Ischemic Stroke due to Middle Cerebral Artery M2 Occlusion with Stent Retriever versus Aspiration: A Multicenter Experience

To examine outcomes for thrombectomy devices used for treatment of acute ischemic stroke (AIS) with middle cerebral artery (MCA) M2 segment emergent large vessel occlusion (ELVO) as the optimal device for such reperfusion is not clearly defined. A retrospective cohort study of consecutive AIS patients with MCA M2 ELVO undergoing thrombectomy from 3 academic medical centers was conducted from October 1999 through June 2016. The patients were divided based on the device utilized. Multivariate analysis of associations between devices (stent retriever or aspiration only [manual or pump aspiration system]) was performed. Primary outcomes were good recanalization (i.e., modified thrombolysis in cerebral infarction score ≥2b) and a favorable modified Rankin scale (mRS) score (i.e. ≤2). The secondary outcome was symptomatic intracerebral hemorrhage (sICH). A total of 197 AIS patients underwent MCA M2 ELVO thrombectomy with either a stent retriever ( = 120) or aspiration only ( = 77). The aspiration-only group utilized either manual ( = 38) or pump aspiration ( = 39). Utilization of a stent retriever over manual aspiration is independently associated with higher odds of a favorable mRS score (OR = 3.2; 95% CI 1.02-9.7) and lower odds of sICH (OR = 0.09; 95% CI 0.03-0.31). Utilization of a stent retriever over a pump aspiration system is independently associated with higher odds of good recanalization (OR = 3.8; 95% CI 1.5-9.6). Utilization of a newer-generation pump aspiration catheter compared to a stent retriever resulted in similar rates of favorable mRS scores, sICH, successful recanalization, and mortality. Utilization of a newer-generation pump aspiration catheter compared to a stent retriever resulted in similar outcomes, but worse outcomes were seen with the manual aspiration technique. These findings need to be confirmed with a large randomized trial utilizing stent retrievers and newer-generation pump aspiration systems

Streamlining door to recanalization processes in endovascular stroke therapy

BACKGROUND: In acute stroke due to large vessel occlusion, faster reperfusion leads to better outcomes. We analyzed the effect of optimization steps aimed to reduce treatment delays at our center. METHODS: Consecutive patients with ischemic stroke treated with endovascular therapy were prospectively analyzed. We divided the patients into pre-optimization (20 April 2012 to 8 October 2013) and post-optimization (9 October 2013 to 29 July 2014) periods. The main interventions included: (1) continuous feedback; (2) standardized immediate emergency department attending to stroke attending communication with interventional team activation for all potential interventions; (3) pre-notification by the emergency medical service; (4) minimizing additional diagnostic testing; (5) direct transport to the CT scanner; (6) transport directly from the CT scanner to the angiography suite. The main metric used to measure improvement was door to groin puncture time (D2P). RESULTS: We included a total of 286 patients (178 pre-optimization, 108 post-optimization). There were no significant differences between major baseline characteristics between the groups with the exception of higher median CT Alberta Stroke Program Early CT Score in the pre-optimization group (p=0.01). Median D2P improved from 105 min pre-optimization to 67 min post-optimization (p=0.0002). Rates of good clinical outcomes (modified Rankin Scale 0-2 at 3 months) were similar in both groups, with a trend toward a better outcome in the post-optimization group in a subgroup analysis of patients with anterior circulation occlusion who received intravenous tissue plasminogen activator. CONCLUSIONS: This pilot study demonstrates that D2P times can be significantly reduced with a standardized multidisciplinary approach. There was no significant difference in the rate of 3-month good outcome, which is most likely due to the small sample size and confounding baseline patient characteristics

Interfacility Transfer Directly to the Neuroangiography Suite in Acute Ischemic Stroke Patients Undergoing Thrombectomy

BACKGROUND AND PURPOSE: In patients identified at referring facilities with acute ischemic stroke caused by a large vessel occlusion, bypassing the emergency department (ED) with direct transport to the neuroangiography suite may safely shorten reperfusion times. METHODS: We conducted a single-center retrospective review of consecutive patients transferred to our facility for consideration of endovascular therapy. Patients were identified as admitted directly to the neuroangiography suite (DAN), transferred to the ED before intra-arterial therapy (ED-IA), and transferred to the ED but did not receive IA therapy (ED-IV). RESULTS: A retrospective review of a prospectively maintained database of transfer patients between January 2013 and October 2016 with large vessel occlusions identified 108 ED-IV patients and 261 patients who underwent mechanical thrombectomy (DAN=111 patients and ED-IA=150 patients). There were no differences in baseline characteristics among the 3 groups. The median computed tomography ASPECTS (Alberta Stroke Program Early CT Score) was lower in the ED-IV group versus the ED-IA and DAN groups (8 versus 9; =0.001). In the DAN versus ED-IA cohort, there were comparable rates of TICI2b/3 recanalization and access to recanalization time. There was significantly faster hospital arrival to groin access time in the DAN cohort (81 minutes versus 22 minutes; =0.001). Functional independence at 90 days was comparable in the DAN versus ED-IA cohorts but worse in the ED-IV group (43% versus 44% versus 22%; =0.001). CONCLUSIONS: DAN is safe, feasible, and associated with faster times of hospital arrival to recanalization. The clinical benefit of this approach should be assessed in a prospective randomized trial

Endovascular Treatment in Acute Basilar Artery Occlusion Stroke: A Brief Practice Update From the Society of Vascular and Interventional Neurology

Background The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee established the “Brief Practice Update” format to provide up‐to‐date recommendations on focused relevant clinical questions. In this Brief Practice Update, we review current evidence and provide recommendations for endovascular treatment (EVT) in patients with acute large‐vessel occlusion of the basilar artery. Methods The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee conducted a systematic review, including the recent randomized clinical trials of EVT for acute ischemic stroke attributable to basilar artery occlusion, and summarized relevant data to provide recommendations for clinical practice. The Guidelines and Practice Standards quality committee reviewed the findings to ensure adherence to the Society of Vascular and Interventional Neurology internal evidence evaluation guidelines before review by the Society of Vascular and Interventional Neurology board members for societal endorsement. Results Evidence favors EVT for basilar artery occlusion in comparison to medical management alone in patients with moderate to severe stroke. We formulated the level of evidence and the class of recommendation in the context of 5 clinical questions. Conclusions In this brief practice statement, we share general recommendations on EVT for acute ischemic stroke attributable to large‐vessel occlusion of the basilar artery. Recent randomized controlled trials, Basilar Artery Occlusion Chinese Endovascular (BAOCHE) trial and Endovascular Treatment for Acute Basilar‐Artery Occlusion (ATTENTION), and a meta‐analysis of all randomized controlled trials support EVT in patients with moderate to severe basilar artery occlusion stroke symptoms