Muhammad S. Hussain

Conscious Sedation Versus General Anesthesia During Endovascular Therapy for Acute Anterior Circulation Stroke: Preliminary Results From a Retrospective, Multicenter Study

Background and Purpose— Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT. Methods— A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death. Results— The mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63–3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23–2.30; P<0.0001) compared with conscious sedation. Conclusions— Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

Sodium imaging intensity increases with time after human ischemic stroke

Establishing time of onset is important in acute stroke management. Current imaging modalities do not allow determination of stroke onset time. Although correlations between sodium magnetic resonance imaging signal intensity within ischemic lesions and time of onset have been shown in animal models, the relation to onset time has not been established in human stroke. Utilizing high‐quality sodium images, we tested the hypothesis that sodium signal intensity increases with time from symptom onset in human ischemic stroke.

The past and future of neuroprotection in cerebral ischaemic stroke.

Following the realization that cerebral tissue may survive for hours after an ischaemic insult, several agents with neuroprotective properties in small-animal models of cerebral ischaemia have been tested in patients with acute ischaemic stroke (AIS). Initial attempts at translating the positive effects of these agents from animal models to patients were unsuccessful, possibly as a result of poorly planned experiments in models of ischaemia, and/or clinical trials of AIS that were not optimized to show a positive effect. Newer neuroprotective agents that are believed to act later in the ischaemic cascade may offer a greater chance of success. However, before these agents can be introduced into clinical practice they must undergo assessment in rodent and large-animal models of AIS and, in particular, the dose-response relationship and the treatment time window should be defined. This should be followed by evaluation in carefully designed clinical trials of adequate power, involving subjects receiving an appropriate dose within an optimum time window following the onset of symptoms. There is hope that such careful strategies may guide continued progress in neuroprotective drug development.

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).

Relationship between sodium intensity and perfusion deficits in acute ischemic stroke

To assess the relationship between sodium signal intensity changes and oligemia, measured with perfusion‐weighted imaging (PWI), in ischemic stroke patients.

Circulating endothelial progenitor cells and age-related white matter changes

Background and Purpose— The objective was to evaluate the relationship between circulating endothelial progenitor cells (EPC) and age-related white matter changes (ARWMC). Endothelial dysfunction plays a role in the development of ARWMC. EPC incorporate into sites endothelial damage and are thought to be involved in the repair of vascular risk factor induced endothelial injury. ARWMC can be evaluated using CT or MRI. Methods— In 172 individuals, circulating EPC were defined by the surface markers CD31 and von Willebrand factor. ARWMC were rated on CT scan using the ARWMC scale and divided into 3 groups based on ARWMC scale score (ARWMC score 0 [none], score 1–10 [mild-to-moderate], score >10 [severe]). Severity of ARWMC was correlated with levels of EPC and vascular risk factors. Results— On univariate analysis, EPC were found to be significantly lower in patients with severe ARWMC (P=0.01). ARWMC were also associated with hypertension (P<0.001), age (P<0.001), creatinine clearance (P=0.031), C-reactive protein (P<0.001), and use of angiotensin-converting enzyme or angiotensin receptor blocker (P=0.004). Multiple logistic regression analysis identified EPC level, age, hypertension, and hypertriglyceridemia as significant independent predictors of severe ARWMC. Conclusions— Levels of circulating EPC were significantly lower in patients with severe ARWMC. Other variables significantly associated with severe ARWMC were age, hypertension, and hypertriglyceridemia. Further study is required to delineate the pathophysiological relationship between EPC, vascular risk factors, and ARWMC.

Does Current Oral Antiplatelet Agent or Subtherapeutic Anticoagulation Use Have an Effect on Tissue-Plasminogen-Activator-Mediated Recanalization Rate in Patients with Acute Ischemic Stroke?

Objective: Our goal is to assess if current antiplatelet (AP) use has an effect on recanalization rate and outcome in acute stroke patients. Methods: We conducted a retrospective analysis of acute stroke patients who received intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and had transcranial Doppler examination within 3 h of symptom onset. The TCD findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion or complete recanalization. Complete recanalization was defined as established Thrombolysis in Brain Ischemia 4 or 5 within 2 h of IV rt-PA. The patients were divided based on their current use of AP agents. Comparisons were made between the different groups based on recanalziation rate, reocclusion and good long-term outcome (mRS ≤2) using χ2 test. Multiple regression analysis was used to identify AP use as a predictor for recanalization and outcome including symptomatic intracranial hemorrhage after controlling for age, baseline NIHSS score, time to treatment, previous vascular event, hypertension and diabetes mellitus. Results: Two hundred and eighty-four patients were included; 154 (54%) males, 130 (46%) females, with a mean age of 69.5 ± 13 years. The median baseline NIHSS score was 16 ± 5. The median time to TCD examination was 131 ± 38 min from symptom onset. The median time to IV rt-PA was 140 ± 34 min. One hundred eighty patients were not on AP prior to their stroke, 76 were on aspirin, 15 were on clopidogrel, 2 were on aspirin-dipyridamole combination, 2 were on both aspirin and clopidogrel, and 9 patients on subtherapeutic coumadin. In patients who were naïve to AP, 68/178 (38.2%) had complete recanalization, whereas in the AP group, 25/91 (28%) had complete recanalization. Patients on aspirin alone had a lower recanalization rate (16/72) as compared to those not on AP (22 vs. 39%) (p = 0.017), while those on clopidogrel had higher rates of complete recanalization (9/19, 60%). There was no difference in the rate of symptomatic intracranial hemorrhages in patients on AP agents as compared to those not on AP (9/180, 5% vs. 9/95, 9.5%) (p = 0.13). A good long-term outcome (mRS ≤2) was achieved in 85/160 (53%) of the patients naïve to AP and in 33/84 (39%) of the patients on AP (p = 0.035). In multiple regression, AP use was not a predictor of either recanalization rate (p = 0.057) or good outcome (p = 0.27). Conclusions: No correlation was found between AP use and recanalization rate and good outcome in patients with acute stroke who received IV rt-PA treatment. Prior AP use should not defer patients from receiving IV rt-PA treatment in an acute stroke setting.

Intra-Arterial Therapy for Acute Ischemic Stroke Under General Anesthesia versus Monitored Anesthesia Care

Background: Recent studies have shown that intra-arterial recanalization therapy (IAT) for acute ischemic stroke (AIS) is associated with worse clinical outcomes when performed under general anesthesia (GA) compared to local anesthesia, with or without conscious sedation. The reasons for this association have not been systematically studied. Methods: We retrospectively reviewed 190 patients who underwent IAT for anterior circulation AIS from January 2008 to December 2012 at our institution. Baseline demographics, vessels involved, acute stroke treatment including intravenous tissue type plasminogen activator (tPA) use, use of GA vs. monitored anesthesia care (MAC), location of thrombus, recanalization grade, radiologic post-procedural intracerebral hemorrhage, and 30-day outcomes were collected. Relevant clinical time points were recorded. Detailed intra-procedural hemodynamics including maximum/minimum heart rate, systolic blood pressure (BP), diastolic BP, mean BP, use of pressors and episodes of hypotension were collected. Our studys outcomes were as follows: in-hospital mortality, 30-day good outcome (mRS ≤2), successful recanalization and radiologic post-procedural intracerebral hemorrhage. Results: Ninety-one patients received GA and 99 patients received MAC. There was no significant difference in the NIHSS score between the two groups but the GA group had a higher number of ICA occlusions (31.9 vs. 18.2%, p = 0.043). The time from the start of anesthesia to incision (23.0 ± 12.5 min vs. 18.7 ± 11.3 min, p = 0.020) and the time from the start of anesthesia to recanalization (110 ± 57.2 vs. 92.3 ± 43.0, p = 0.045) was longer in the GA group. The time from incision to recanalization was not significantly different between the two groups. mRS 0-2 was achieved in 22.8% of patients in the MAC group compared to 14.9% in GA (p = 0.293). Higher mortality was seen in the GA group (25.8 vs. 13.3%, p = 0.040). Successful recanalization (TICI 2b-3) was similar between the GA and MAC (57.8 vs. 48.5%, p = 0.182) groups, but GA had a higher number of parenchymal hematomas (26.3 vs. 10.1%, p = 0.003). There was no difference in the intra-procedural hemodynamic variables between the GA and MAC groups. Anesthesia type was an independent predictor for mortality (along with age and initial NIHSS), and the only independent predictor for parenchymal hematomas, with MAC being protective for both. Conclusion: Our study has confirmed previous findings of GA being associated with poorer outcomes and higher mortality in patients undergoing IAT for AIS. Detailed analysis of intra-procedural hemodynamics did not reveal any significant difference between the two groups. Parenchymal hematoma was the major driver of the difference in outcomes.

Research Into Neuroprotection Must Continue … but With a Different Approach

Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACP Section Editors: nnNeuroprotective agents disrupting the ischemic cascade and salvaging the ischemic penumbra are being explored as a potential therapeutic option for stroke. Although a number of agents are neuroprotective in animal studies, none of the human trials have been positive, with the exception of the SAINT I trial.1 Unfortunately, the follow-up SAINT II trial had a negative result,2 and a great deal of pessimism regarding the future of neuroprotection has been generated. However, before abandoning neuroprotection as a strategy, it is important to examine where research in neuroprotection has brought us and how we can better design future animal and clinical studies.nnThe main reason for failure has been poor translation from animal studies to clinical trials. Clinical trials often had prolonged therapeutic windows, small sample sizes, and failed to achieve adequate plasma levels of study medications. These problems lead to the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations,3,4 which have greatly improved …

Headache following intracranial neuroendovascular procedures

(Headache 2012;52:739‐748)