Ava L. Liberman

Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?

SummaryAn unintended consequence of rapid thrombolysis may be more frequent treatment of stroke mimics, nonvascular conditions that simulate stroke. We explored the relationship between door-to-needle (DTN) times and thrombolysis of stroke mimics at a single academic center by analyzing consecutive quartiles of patients who were treated with IV tissue plasminogen activator for suspected stroke from January 1, 2010 to February 28, 2014. An increase in the proportion of stroke mimic patients (6.7% in each of the 1st and 2nd, 12.9% in the 3rd, and 30% in the last consecutive case quartile; p = 0.03) and a decrease in median DTN time from 89 to 56 minutes (p < 0.01) was found. As more centers reduce DTN times, the rates of stroke mimic treatment should be carefully monitored.

Diagnostic Yield of Pelvic Magnetic Resonance Venography in Patients With Cryptogenic Stroke and Patent Foramen Ovale

Background and Purpose— Paradoxical embolization is frequently posited as a mechanism of ischemic stroke in patients with patent foramen ovale. Several studies have suggested that the deep lower extremity and pelvic veins might be an embolic source in cryptogenic stroke (CS) patients with patent foramen ovale. Methods— Consecutive adult patients with ischemic stroke or transient ischemic attack and a patent foramen ovale who underwent pelvic magnetic resonance venography as part of an inpatient diagnostic evaluation were included in this single-center retrospective observational study to determine pelvic and lower extremity (LE) deep venous thrombosis (DVT) prevalence in CS versus non-CS stroke subtypes. Results— Of 131 patients who met inclusion criteria, 126 (96.2%) also had LE duplex ultrasound data. DVT prevalence overall was 7.6% (95% confidence interval, 4.1–13.6), pelvic DVT 1.5% (95% confidence interval, 0.1–5.8), and LE DVT 7.1% (95% confidence interval, 3.6–13.2). One patient with a pelvic DVT also had a LE DVT. Comparing patients with CS (n=98) with non-CS subtypes (n=33), there was no significant difference in the prevalence of pelvic DVT (2.1% versus 0%, P=1), LE DVT (6.2% versus 10.3%, P=0.43), or any DVT (7.2% versus 9.1%, P=0.71). Conclusions— Among patients with ischemic stroke/transient ischemic attack and patent foramen ovale, the majority of detected DVTs were in LE veins rather than the pelvic veins and did not differ by stroke subtype. The routine inclusion of pelvic magnetic resonance venography in the diagnostic evaluation of CS warrants further prospective investigation.

Stroke Chameleons and Stroke Mimics in the Emergency Department

Purpose of ReviewWe discuss the frequency of stroke misdiagnosis in the emergency department (ED), identify common diagnostic pitfalls, describe strategies to reduce diagnostic error, and detail ongoing research.Recent FindingsThe National Academy of Medicine has re-defined and highlighted the importance of diagnostic errors for patient safety. Recent rates of stroke under-diagnosis (false-negative cases, “stroke chameleons”) range from 2–26% and 30–43% for stroke over-diagnosis (false-positive cases, “stroke mimics”). Failure to diagnosis stroke can preclude time-sensitive treatments and has been associated with poor outcomes. Strategies have been developed to improve detection of posterior circulation stroke syndromes, but ongoing work is needed to reduce under-diagnosis in other atypical stroke presentations. The published rates of harm associated with stroke over-diagnosis, particularly thrombolysis of stroke mimics, remain low.SummaryAdditional strategies to improve the accuracy of stroke diagnosis should focus on rapid clinical reasoning in the time-sensitive setting of acute ischemic stroke and identifying imperfections in the healthcare system which may contribute to diagnostic error.

Cryptogenic Stroke: How to Define It? How to Treat It?

Stroke is a leading cause of disability worldwide. Cryptogenic strokes (CS) account for almost a quarter of ischemic strokes despite modern diagnostic evaluation. A working definition of CS based on stroke classification systems is essential for accurate conceptualization of this common entity. Mechanistic categories (potential paradoxical embolism; atherosclerotic disease of the aorta or supra-aortic vasculature; and occult arrhythmia) should aide in parsing the often heterogeneous mix of conditions included in the CS subtype. Despite efforts to unravel mechanisms of CS, specific or targeted recurrent stroke prevention strategies are lacking. For example, recent trials have shown no clear benefit of patent foramen ovale closure in stroke prevention after CS. There are promising ongoing clinical trials that will address appropriate diagnostic evaluations in CS as well as novel therapeutic interventions. Overall, a standardized approach must be framed to diagnose and manage patients with CS and guide clinical practice and future research.

Rapid development of 9 cerebral aneurysms in Varicella-Zoster virus vasculopathy

A patient with zoster in multiple dermatomes, severe headache, and normal magnetic resonance angiography (MRA) and 4-vessel digital subtraction angiogram (DSA) developed 9 anterior circulation aneurysms 2 months later. Antiviral treatment resulted in clinical improvement, size reduction of most aneurysms, and complete resolution of the 2 largest aneurysms.

Symptom-Disease Pair Analysis of Diagnostic Error (SPADE): a conceptual framework and methodological approach for unearthing misdiagnosis-related harms using big data

Background The public health burden associated with diagnostic errors is likely enormous, with some estimates suggesting millions of individuals are harmed each year in the USA, and presumably many more worldwide. According to the US National Academy of Medicine, improving diagnosis in healthcare is now considered ‘a moral, professional, and public health imperative.’ Unfortunately, well-established, valid and readily available operational measures of diagnostic performance and misdiagnosis-related harms are lacking, hampering progress. Existing methods often rely on judging errors through labour-intensive human reviews of medical records that are constrained by poor clinical documentation, low reliability and hindsight bias. Methods Key gaps in operational measurement might be filled via thoughtful statistical analysis of existing large clinical, billing, administrative claims or similar data sets. In this manuscript, we describe a method to quantify and monitor diagnostic errors using an approach we call ‘Symptom-Disease Pair Analysis of Diagnostic Error’ (SPADE). Results We first offer a conceptual framework for establishing valid symptom-disease pairs illustrated using the well-known diagnostic error dyad of dizziness-stroke. We then describe analytical methods for both look-back (case–control) and look-forward (cohort) measures of diagnostic error and misdiagnosis-related harms using ‘big data’. After discussing the strengths and limitations of the SPADE approach by comparing it to other strategies for detecting diagnostic errors, we identify the sources of validity and reliability that undergird our approach. Conclusion SPADE-derived metrics could eventually be used for operational diagnostic performance dashboards and national benchmarking. This approach has the potential to transform diagnostic quality and safety across a broad range of clinical problems and settings.

Door-to-Needle Delays in Minor Stroke: A Causal Inference Approach

Background and Purpose— Thrombolysis rates among minor stroke (MS) patients are increasing because of increased recognition of disability in this group and guideline changes regarding treatment indications. We examined the association of delays in door-to-needle (DTN) time with stroke severity. Methods— We performed a retrospective analysis of all stroke patients who received intravenous tissue-type plasminogen activator in our emergency department between July 1, 2011, and February 29, 2016. Baseline characteristics and DTN were compared between MS (National Institutes of Health Stroke Scale score ⩽5) and nonminor strokes (National Institutes of Health Stroke Scale score >5). We applied causal inference methodology to estimate the magnitude and mechanisms of the causal effect of stroke severity on DTN. Results— Of 315 patients, 133 patients (42.2%) had National Institutes of Health Stroke Scale score ⩽5. Median DTN was longer in MS than nonminor strokes (58 versus 53 minutes; P=0.01); fewer MS patients had DTN ⩽45 minutes (19.5% versus 32.4%; P=0.01). MS patients were less likely to use emergency medical services (EMS; 62.6% versus 89.6%, P<0.01) and to receive EMS prenotification (43.9% versus 72.4%; P<0.01). Causal analyses estimated MS increased average DTN by 6 minutes, partly through mode of arrival. EMS prenotification decreased average DTN by 10 minutes in MS patients. Conclusions— MS had longer DTN times, an effect partly explained by patterns of EMS prenotification. Interventions to improve EMS recognition of MS may accelerate care.

Symptomatic Carotid Occlusion Is Frequently Associated With Microembolization

Background and Purpose— Symptomatic carotid artery disease is associated with significant morbidity and mortality. The pathophysiologic mechanisms of cerebral ischemia among patients with carotid occlusion remain underexplored. Methods— We conducted a prospective observational cohort study of patients hospitalized within 7 days of ischemic stroke or transient ischemic attack because of ≥50% carotid artery stenosis or occlusion. Transcranial Doppler emboli detection was performed in the middle cerebral artery ipsilateral to the symptomatic carotid. We describe the prevalence of microembolic signals (MES), characterize infarct topography, and report clinical outcomes at 90 days. Results— Forty-seven patients, 19 with carotid occlusion and 28 with carotid stenosis, had complete transcranial Doppler recordings and were included in the final analysis. MES were present in 38%. There was no difference in MES between those with carotid occlusion (7/19, 37%) compared with stenosis (11/28, 39%; P=0.87). In patients with radiographic evidence of infarction (n=39), 38% had a watershed pattern of infarction, 41% had a nonwatershed pattern, and 21% had a combination. MES were present in 40% of patients with a watershed pattern of infarction. Recurrent cerebral ischemia occurred in 9 patients (19%; 6 with transient ischemic attack, 3 with ischemic stroke). There was no difference in the rate of recurrence in those with compared to those without MES. Conclusions— Cerebral embolization plays an important role in the pathophysiology of ischemia in both carotid occlusion and stenosis, even among patients with watershed infarcts. The role of aggressive antithrombotic and antiplatelet therapy for symptomatic carotid occlusions may warrant further investigation given our findings.

Risk of Pulmonary Embolism After Cerebral Venous Thrombosis

Background and Purpose— Cerebral vein thrombosis (CVT) is a type of venous thromboembolism. Whether the risk of pulmonary embolism (PE) after CVT is similar to the risk after deep venous thrombosis (DVT) is unknown. Methods— We performed a retrospective cohort study using administrative data from all emergency department visits and hospitalizations in California, New York, and Florida from 2005 to 2013. We identified patients with CVT or DVT and the outcome of PE using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes. Kaplan–Meier survival statistics and Cox proportional hazards models were used to compare the risk of PE after CVT versus PE after DVT. Results— We identified 4754 patients with CVT and 241 276 with DVT. During a mean follow-up of 3.4 (±2.4) years, 138 patients with CVT and 23 063 with DVT developed PE. CVT patients were younger, more often female, and had fewer risk factors for thromboembolism than patients with DVT. During the index hospitalization, the rate of PE was 1.4% (95% confidence interval [CI], 1.1%–1.8%) in patients with CVT and 6.6% (95% CI, 6.5%–6.7%) in patients with DVT. By 5 years, the cumulative rate of PE after CVT was 3.4% (95% CI, 2.9%–4.0%) compared with 10.9% (95% CI, 10.8%–11.0%; P<0.001) after DVT. CVT was associated with a lower adjusted hazard of PE than DVT (hazard ratio, 0.26; 95% CI, 0.22–0.31). Conclusion— The risk of PE after CVT was significantly lower than the risk after DVT. Among patients with CVT, the greatest risk for PE was during the index hospitalization.

International Classification of Diseases, Ninth Revision (ICD-9) Diagnosis Codes Can Identify Cerebral Venous Thrombosis in Hospitalized Adults

Background: Cerebral venous thrombosis (CVT) is a relatively rare and understudied disease. We sought to determine the accuracy of International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes to identify CVT. Methods: Retrospective chart review using the electronic medical record (EMR) to identify all patients discharged with CVT following admission or emergency department visit from May 1, 2010 to May 1, 2015 at our center. Results: We identified 111 patients with an ICD-9 discharge diagnosis code of 325.0 (cerebral sinovenous thrombosis, excluding nonpyogenic cases and cases associated with pregnancy and the puerperium), 437.6 (CVT of nonpyogenic origin), or 671.5 (CVT complicating pregnancy, childbirth, or the puerperium) in any position. Of these 111 patients, 84 (75.7%) had confirmed CVT after EMR review. Searching outpatient and radiology records, we found an additional 24 patients with CVT who were not identified via query of ICD-9 discharge diagnosis codes. The ICD-9 codes 325.0, 437.6, or 671.5 in any position had a combined sensitivity of 77.8% and specificity of 92.7%; in the primary position, they had a sensitivity of 28.7% and specificity of 98.3%. Conclusion: The ICD-9 codes 325.0, 437.6, and 671.5 can be used to identify CVT with acceptable sensitivity and specificity.