Brian Katz

Design and Validation of a Prehospital Scale to Predict Stroke Severity: Cincinnati Prehospital Stroke Severity Scale

Background and Purpose— We derived and validated the Cincinnati Prehospital Stroke Severity Scale (CPSSS) to identify patients with severe strokes and large vessel occlusion (LVO). Methods— CPSSS was developed with regression tree analysis, objectivity, anticipated ease in administration by emergency medical services personnel and the presence of cortical signs. We derived and validated the tool using the 2 National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator Stroke Study trials and Interventional Management of Stroke III (IMS III) Trial cohorts, respectively, to predict severe stroke (National Institutes of Health Stroke Scale [NIHSS] ≥15) and LVO. Standard test characteristics were determined and receiver operator curves were generated and summarized by the area under the curve. Results— CPSSS score ranges from 0 to 4; composed and scored by individual NIHSS items: 2 points for presence of conjugate gaze (NIHSS ≥1); 1 point for presence of arm weakness (NIHSS ≥2); and 1 point for presence abnormal level of consciousness commands and questions (NIHSS level of consciousness ≥1 each). In the derivation set, CPSSS had an area under the curve of 0.89; score ≥2 was 89% sensitive and 73% specific in identifying NIHSS ≥15. Validation results were similar with an area under the curve of 0.83; score ≥2 was 92% sensitive, 51% specific, a positive likelihood ratio of 3.3, and a negative likelihood ratio of 0.15 in predicting severe stroke. For 222 of 303 IMS III subjects with LVO, CPSSS had an area under the curve of 0.67; a score ≥2 was 83% sensitive, 40% specific, positive likelihood ratio of 1.4, and negative likelihood ratio of 0.4 in predicting LVO. Conclusions— CPSSS can identify stroke patients with NIHSS ≥15 and LVO. Prospective prehospital validation is warranted.

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.

Prospective Prehospital Evaluation of the Cincinnati Stroke Triage Assessment Tool

Abstract Background and Purpose: A simple, easily adoptable scale with good performance characteristics is needed for EMS providers to appropriately triage suspected stroke patients to comprehensive stroke centers (CSC). Many existing tools are complex, require substantial training, or have not been prospectively validated in the prehospital setting. We describe the feasibility and effectiveness of prehospital implementation of our previously retrospectively derived and validated Cincinnati Stroke Triage Assessment Tool (C-STAT) to identify subjects with severe stroke (NIHSS ≥15) among all prehospital patients with clinical suspicion of stroke/TIA. Secondarily, we evaluated the tools ability to identify subjects with NIHSS ≥10, large vessel occlusion (LVO), or needing services available only at a CSC. Methods: Without formalized training, Cincinnati Fire Department providers performed standard stroke screening (“face, arm, speech, time;” FAST) and C-STAT as part of their assessment of suspected stroke/TIA patients. Outcomes for patients brought to the regions only CSC or assessed by the regional stroke team were determined through structured chart review by a stroke team nurse. C-STAT test characteristics for each outcome were calculated with 95% confidence intervals. Results: Complete prehospital and outcome data were available for 58 FAST-positive subjects among 158 subjects with prehospital suspicion for stroke/TIA. Subjects were excluded if FAST was negative (n = 22), FAST or C-STAT was incompletely documented (n = 24), if the patient was taken to a non-CSC and did not receive a stroke team consult (n = 48), or if outcome data were missing (n = 6). C-STAT sensitivity and specificity for each outcome were: NIHSS ≥ 15, 77% (95% CI 46–95) and 84% (95% CI 69–93); NIHSS ≥10, 64% (95% CI 41–83) and 91% (95% CI 76–98); LVO, 71% (95% CI 29–96) and 70% (95% CI 55–83); overall CSC need 57% (95% CI 34–78) and 79% (95% CI 61–91). Conclusion: In this pilot prospective evaluation performed in the prehospital setting by EMS providers without formalized training, C-STAT is comparable to other published tools in test characteristics and may inform appropriate CSC triage beyond LVO ascertainment alone.

Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Full Dose Regimen (CLEAR-FDR Stroke Trial)

Background and Purpose The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose recombinant tissue plasminogen activator (rt-PA) plus the glycoprotein 2b/3a inhibitor, eptifibatide, in acute ischemic stroke (AIS) compared to rt-PA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full dose rt-PA plus eptifibatide.Background and Purpose— The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full-dose r-tPA plus eptifibatide. Methods— CLEAR-FDR was a single-arm, prospective, open-label, multisite study. Patients aged 18 to 85 years treated with 0.9 mg/kg IV r-tPA within 3 hours of symptom onset were enrolled. After obtaining consent, eptifibatide (135 &mgr;g/kg bolus and 2-hour infusion at 0.75 &mgr;g/kg per minute) was administered. The primary end point was the proportion of patients who experienced sICH within 36 hours. An independent clinical monitor adjudicated if an sICH had occurred and an independent neuroradiologist reviewed all images. The stopping rule was 3 sICHs within the first 19 patients or 4 sICHs within 29 patients. Results— From October 2013 to December 2014, 27 patients with AIS were enrolled. Median age was 73 years (range, 34–85; interquartile range, 65–80) and median National Institute of Health stroke scale score was 12 (range, 6–26; interquartile range, 9–16). One sICH (3.7%; 95% confidence interval, 0.7%–18%) was observed. Conclusions— These results demonstrate comparable safety of full-dose r-tPA plus eptifibatide with historical rates of sICH with r-tPA alone and support proceeding with a phase 3 trial evaluating full-dose r-tPA combined with eptifibatide to improve outcomes after AIS.

Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study

Background and Purpose— The American Stroke Association recommends that Emergency Medical Service bypass acute stroke–ready hospital (ASRH)/primary stroke center (PSC) for comprehensive stroke centers (CSCs) when transporting appropriate stroke patients, if the additional travel time is ⩽15 minutes. However, data on additional transport time and the effect on hospital census remain unknown. Methods— Stroke patients ≥20 years old who were transported from home to an ASRH/PSC or CSC via Emergency Medical Service in 2010 were identified in the Greater Cincinnati area population of 1.3 million. Addresses of all patients’ residences and hospitals were geocoded, and estimated travel times were calculated. We estimated the mean differences between the travel time for patients taken to an ASRH/PSC and the theoretical time had they been transported directly to the region’s CSC. Results— Of 929 patients with geocoded addresses, 806 were transported via Emergency Medical Service directly to an ASRH/PSC. Mean additional travel time of direct transport to the CSC, compared with transport to an ASRH/PSC, was 7.9±6.8 minutes; 85% would have ⩽15 minutes added transport time. Triage of all stroke patients to the CSC would have added 727 patients to the CSC’s census in 2010. Limiting triage to the CSC to patients with National Institutes of Health Stroke Scale score of ≥10 within 6 hours of onset would have added 116 patients (2.2 per week) to the CSC’s annual census. Conclusions— Emergency Medical Service triage to CSCs based on stroke severity and symptom duration may be feasible. The impact on stroke systems of care and patient outcomes remains to be determined and requires prospective evaluation.

Letter by Adeoye et al Regarding Article, "Prehospital Acute Stroke Severity Scale to Predict Large Artery Occlusion: Design and Comparison With Other Scales".

We read with interest the article by Hastrup et al1 titled “Prehospital Acute Stroke Severity Scale to Predict Large Artery Occlusion.” Using a Danish registry of 3127 patients with acute ischemic stroke, the PASS (Prehospital Acute Stroke Severity) score was derived and tested for its ability to predict arterial large vessel occlusion. Three items from the National Institutes of Health (NIH) stroke scale were identified as predictors of large vessel occlusion: abnormal gaze, arm weakness, and level of consciousness questions. In the derivation cohort, the PASS scale had …

Teaching NeuroImages: Seeing double Intercavernous sinus dural arteriovenous fistula causing bilateral abducens palsy

A 64-year-old woman developed sudden onset of diplopia, headache, and bilateral abducens palsy. MRI revealed no intracranial mass, ischemia, or intraorbital pathology. Magnetic resonance angiography suggested bilateral carotid cavernous fistulas (CCFs, figure 1). Digital substraction angiogram revealed an intercavernous sinus dural arteriovenous fistula (DAVF), which was successfully embolized (figure 2). By 3-month follow-up, her …