Achala Vagal

Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial

BACKGROUND The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase (recombinant tissue plasminogen activator) alone for moderate or severe ischaemic strokes. Late reperfusion of tissue that was no longer salvageable could be one explanation, as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome. We sought to validate this association in a preplanned analysis of data from the IMS III trial. METHODS We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion (score on Thrombolysis in Cerebral Infarction scale of grade 2-3) during the endovascular procedure (within 7 h of symptom onset). We used logistic regression to model good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) as a function of the time to reperfusion. We prespecified variables to be considered for adjustment, including age, baseline National Institutes of Health Stroke Scale score, sex, and baseline blood glucose concentration. FINDINGS Of 240 patients who were otherwise eligible for inclusion in our analysis, 182 (76%) achieved angiographic reperfusion. Mean time from symptom onset to reperfusion (ie, procedure end) was 325 min (SD 52). Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome (unadjusted relative risk for every 30-min delay 0·85 [95% CI 0·77-0·94]; adjusted relative risk 0·88 [0·80-0·98]). INTERPRETATION Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke. Rapid reperfusion could be crucial for the success of future acute endovascular trials. FUNDING US National Institutes of Health and National Institute of Neurological Disorders and Stroke.

The Acetazolamide Challenge: Techniques and Applications in the Evaluation of Chronic Cerebral Ischemia

SUMMARY: The acetazolamide (ACZ) challenge test is a useful clinical tool and a reliable predictor of critically reduced perfusion. In patients with chronic steno-occlusive disease, the ability to maintain normal cerebral blood flow by reducing vascular resistance secondary to autoregulatory vasodilation is compromised. Identification of the presence and degree of autoregulatory vasodilation (reflecting the cerebrovascular reserve) is a significant prognostic factor in patients with chronic cerebrovascular disease. The pharmacologic challenge of a vasodilatory stimulus such as ACZ can also be used to optimize the treatment strategies for these patients. The pathophysiology, methods, and clinical applications of the ACZ challenge test are discussed in this article.

Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke–Enhanced Regimen Stroke Trial

Background and Purpose— In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke–Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. Methods— CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ⩽1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. Results— Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01–1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ⩽1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70–4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51–3.76; P=0.52). Conclusions— The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.

Overnight Preliminary Head CT Interpretations Provided by Residents: Locations of Misidentified Intracranial Hemorrhage

BACKGROUND AND PURPOSE: Our aim was to determine the patterns of error of radiology residents in the detection of intracranial hemorrhage on head CT examinations while on call. Follow-up studies were reviewed to determine if there was any adverse effect on patient outcome as a result of these preliminary interpretations. MATERIALS AND METHODS: Radiology residents prospectively interpreted 22,590 head CT examinations while on call from January 1, 2002, to July 31, 2006. The following morning, the studies were interpreted by staff neuroradiologists, and discrepancies from the preliminary report were documented. Patients’ charts were reviewed for clinical outcomes and any imaging follow-up. RESULTS: There were a total of 1037 discrepancies identified, of which 141 were due to intracranial hemorrhage. The most common types of intracranial hemorrhage that were missed were subdural and subarachnoid hemorrhage occurring in 39% and 33% of the cases, respectively. The most common location for missed subdural hemorrhage was either parafalcine or frontal. The most common location of missed subarachnoid hemorrhage was in the interpeduncular cistern. There was 1 case of nontraumatic subarachnoid hemorrhage that was not described in the preliminary report. Fourteen patients were brought back to the emergency department for short-term follow-up imaging after being discharged. We did not observe any adverse clinical outcomes that resulted from a discrepant reading. CONCLUSION: Discrepancies due to intracranial hemorrhage are usually the result of subdural or subarachnoid hemorrhage. A more complete understanding of the locations of the missed hemorrhage can hopefully help decrease the discrepancy rate to help improve patient care.

Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities.

Background and Purpose— The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. Methods— This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. Results— The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. Conclusions— Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

Surgical management of traumatic brain injury: a comparative-effectiveness study of 2 centers

OBJECT Mass lesions from traumatic brain injury (TBI) often require surgical evacuation as a life-saving measure and to improve outcomes, but optimal timing and surgical technique, including decompressive craniectomy, have not been fully defined. The authors compared neurosurgical approaches in the treatment of TBI at 2 academic medical centers to document variations in real-world practice and evaluate the efficacies of different approaches on postsurgical course and long-term outcome. METHODS Patients 18 years of age or older who required neurosurgical lesion evacuation or decompression for TBI were enrolled in the Co-Operative Studies on Brain Injury Depolarizations (COSBID) at Kings College Hospital (KCH, n = 27) and Virginia Commonwealth University (VCU, n = 24) from July 2004 to March 2010. Subdural electrode strips were placed at the time of surgery for subsequent electrocorticographic monitoring of spreading depolarizations; injury characteristics, physiological monitoring data, and 6-month outcomes were collected prospectively. CT scans and medical records were reviewed retrospectively to determine lesion characteristics, surgical indications, and procedures performed. RESULTS Patients enrolled at KCH were significantly older than those enrolled at VCU (48 vs 34 years, p < 0.01) and falls were more commonly the cause of TBI in the KCH group than in the VCU group. Otherwise, KCH and VCU patients had similar prognoses, lesion types (subdural hematomas: 30%-35%; parenchymal contusions: 48%-52%), signs of mass effect (midline shift ≥ 5 mm: 43%-52%), and preoperative intracranial pressure (ICP). At VCU, however, surgeries were performed earlier (median 0.51 vs 0.83 days posttrauma, p < 0.05), bone flaps were larger (mean 82 vs 53 cm(2), p < 0.001), and craniectomies were more common (performed in 75% vs 44% of cases, p < 0.05). Postoperatively, maximum ICP values were lower at VCU (mean 22.5 vs 31.4 mm Hg, p < 0.01). Differences in incidence of spreading depolarizations (KCH: 63%, VCU: 42%, p = 0.13) and poor outcomes (KCH: 54%, VCU: 33%, p = 0.14) were not significant. In a subgroup analysis of only those patients who underwent early (< 24 hours) lesion evacuation (KCH: n = 14; VCU: n = 16), however, VCU patients fared significantly better. In the VCU patients, bone flaps were larger (mean 85 vs 48 cm(2) at KCH, p < 0.001), spreading depolarizations were less common (31% vs 86% at KCH, p < 0.01), postoperative ICP values were lower (mean: 20.8 vs 30.2 mm Hg at KCH, p < 0.05), and good outcomes were more common (69% vs 29% at KCH, p < 0.05). Spreading depolarizations were the only significant predictor of outcome in multivariate analysis. CONCLUSIONS This comparative-effectiveness study provides evidence for major practice variation in surgical management of severe TBI. Although ages differed between the 2 cohorts, the results suggest that a more aggressive approach, including earlier surgery, larger craniotomy, and removal of bone flap, may reduce ICP, prevent cortical spreading depolarizations, and improve outcomes. In particular, patients requiring evacuation of subdural hematomas and contusions may benefit from decompressive craniectomy in conjunction with lesion evacuation, even when elevated ICP is not a factor in the decision to perform surgery.

Time to Angiographic Reperfusion in Acute Ischemic Stroke Decision Analysis

Background and Purpose— Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion. Methods— We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach. Results— In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach. Conclusions— In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions.

Cardiopulmonary Imaging in Sarcoidosis

Sarcoidosis is a disease with protean clinical manifestations ranging from no symptoms to sudden death. Radiologic tests are often the key to diagnosis. In this article, the authors review current imaging techniques and discuss emerging technologies used in the noninvasive cardiopulmonary evaluation of the patient who has sarcoidosis.

Increasing Use of Computed Tomographic Perfusion and Computed Tomographic Angiograms in Acute Ischemic Stroke From 2006 to 2010

Background and Purpose— Our objective was to study nationwide utilization trends of computed tomographic (CT) angiogram (CTA) and CT perfusion (CTP) in acute ischemic stroke and particularly in the context of use of reperfusion therapies. Methods— We reviewed the Premier Perspective Database for ischemic stroke–related hospitalizations of adult patients during a 5-year period, 2006 to 2010. Use of multimodal CT-based imaging and reperfusion therapies was determined through the procedure and billing codes. Logistic regression was used to identify predictors of utilization of imaging studies and reperfusion treatments. Results— An increasing proportion of ischemic strokes received CTA each year: 3.8% in 2006, 5.6% in 2007, 6.5% in 2008, 7.5% in 2009, and 9.1% in 2010 (P<0.0001). The proportion of acute strokes that were imaged with CTP imaging also increased each year: 0.05% in 2006, 0.05% in 2007, 0.9% in 2008, 2.2% in 2009, and 2.9% in 2010 (P<0.0001). Reperfusion treatment was more common among those who were imaged with CTA (13.0%) and CTP (17.6%) compared with those with CT head alone (4.0%; P<0.0001). Specifically, higher rates of recombinant tissue-type plasminogen activator were observed in CTA (10.2%) and CTP (11.4%) compared with those with CT head alone (3.8%; P<0.0001). Similarly, higher rates of mechanical embolectomy were observed in CTA (2.8%) and CTP (6.3%) compared with those with CT head alone (0.2%; P<0.0001). Conclusions— There was a marked increase in the rate of CTA and CTP studies in setting of acute ischemic stroke from 2006 to 2010, and both modalities were associated with increased reperfusion therapy use.

Promotion as a Clinician Educator in Academic Radiology Departments: Guidelines at Three Major Institutions

Faculty promotion within an academic department of radiology may place emphasis on scientific research, administrative contributions, educational contributions, or a combination of all endeavors that enrich the department and further its academic mission. For those departments considering the establishment of a promotion pathway that emphasizes teaching talents and education-oriented research, the authors provide examples of three different clinician-educator faculty appointment and promotion schemes. Faculty development and defining scholarly work as a clinician-educator, as well as documentation of academic productivity within this pathway, are discussed.