Michael P. Lerario

Magnetic resonance angiography detection of abnormal carotid artery plaque in patients with cryptogenic stroke.

Background Magnetic resonance imaging of carotid plaque can aid in stroke risk stratification in patients with carotid stenosis. However, the prevalence of complicated carotid plaque in patients with cryptogenic stroke is uncertain, especially as assessed by plaque imaging techniques routinely included in acute stroke magnetic resonance imaging protocols. We assessed whether the magnetic resonance angiography–defined presence of intraplaque high-intensity signal (IHIS), a marker of intraplaque hemorrhage, is associated with ipsilateral cryptogenic stroke. Methods and Results Cryptogenic stroke patients with magnetic resonance imaging evidence of unilateral anterior circulation infarction and without hemodynamically significant (≥50%) stenosis of the cervical carotid artery were identified from a prospective stroke registry at a tertiary-care hospital. High-risk plaque was assessed by evaluating for IHIS on routine magnetic resonance angiography source images using a validated technique. To compare the presence of IHIS on the ipsilateral versus contralateral side within individual patients, we used McNemar’s test for correlated proportions. A total of 54 carotid arteries in 27 unique patients were included. A total of 6 patients (22.2%) had IHIS-positive nonstenosing carotid plaque ipsilateral to the side of ischemic stroke compared to 0 patients who had IHIS-positive carotid plaques contralateral to the side of stroke (P=0.01). Stroke severity measures, diagnostic evaluations, and prevalence of vascular risk factors were not different between the IHIS-positive and IHIS-negative groups. Conclusions Our findings suggest that a proportion of strokes classified as cryptogenic may be mechanistically related to complicated, nonhemodynamically significant cervical carotid artery plaque that can easily be detected by routine magnetic resonance imaging/magnetic resonance angiography acute stroke protocols.

Temporal relationship between infective endocarditis and stroke.

Objective: Stroke frequently complicates infective endocarditis (IE). However, the temporal relationship between these diseases is uncertain. Methods: We performed a retrospective study of adult patients hospitalized for IE between July 1, 2007, and June 30, 2011, at nonfederal acute care hospitals in California. Previously validated diagnosis codes were used to identify the primary composite outcome of ischemic or hemorrhagic stroke during discrete 1-month periods from 6 months before to 6 months after the diagnosis of IE. The odds of stroke in these periods were compared with the odds of stroke in the corresponding 1-month period 2 years earlier, which was considered the baseline risk of stroke. Results: Among 17,926 patients with IE, 2,275 strokes occurred within the 12-month period surrounding the diagnosis of IE. The risk of stroke was highest in the month after diagnosis of IE (1,640 vs 17 strokes in the corresponding month 2 years prior). This equaled an absolute risk increase of 9.1% (95% confidence interval 8.6%–9.5%) and an odds ratio of 96.5 (95% confidence interval 60.1–166.0). Stroke risk was significantly increased beginning 4 months before the diagnosis of IE and lasting 5 months afterward. Similar temporal patterns were seen when ischemic and hemorrhagic strokes were considered separately. Conclusions: The association between IE and stroke persists for longer than previously reported. Most diagnoses of stroke and IE are made close together in time, but a period of heightened stroke risk becomes apparent several months before the diagnosis of IE and lasts for several months afterward.

Rates of Spinal Cord Infarction After Repair of Aortic Aneurysm or Dissection

Background and Purpose— The rate of spinal cord infarction (SCI) after surgical or endovascular repair of an aortic aneurysm or dissection is unclear. Methods— Using administrative claims data, we identified adult patients discharged from nonfederal acute care hospitals in California, New York, and Florida who underwent surgical or endovascular repair of an aortic aneurysm or dissection between 2005 and 2013. Patients with SCI diagnosed before the aortic repair were excluded. Our primary outcome was an SCI during the index hospitalization for aortic repair. Descriptive statistics were used to estimate crude rates of SCI. Analyses were stratified by whether the aneurysm or dissection had ruptured and by type of repair (surgical versus endovascular). Results— We identified 91 212 patients who had repair of an aortic aneurysm or dissection. SCI occurred in 235 cases (0.26%; 95% confidence interval [CI], 0.22%–0.29%). In patients with ruptured aneurysm or dissection, the rate of SCI was 0.74% (95% CI, 0.60%–0.88%) compared with 0.16% (95% CI, 0.13%–0.19%) with unruptured aneurysm. In secondary analyses, rates of SCI were similar after endovascular repair (0.91%; 95% CI, 0.62%–1.19%) compared with surgical repair (0.68%; 95% CI, 0.53%–0.83%; P=0.147) of ruptured aortic aneurysm or dissection; however, rates of SCI were higher after surgical repair (0.20%; 95% CI, 0.15%–0.25%) versus endovascular repair (0.11%; 95% CI, 0.08%–0.14%; P<0.001) of unruptured aneurysm. Conclusions— SCI occurs in ≈1 in 130 patients undergoing aortic dissection or ruptured aortic aneurysm repair and in 1 in 600 patients undergoing unruptured aortic aneurysm repair.

Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation

Background We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation. Materials and Methods Using discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke. Results Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5–8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5–4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0–2.1%) in those without intracranial hemorrhage. After adjustment for the CHA2DS2-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6–2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5–1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA2DS2-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA2DS2-VASc score of 9. Conclusions In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA2DS2-VASc scores.

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.

Association Between Troponin Levels and Embolic Stroke of Undetermined Source

Background Our aim was to determine whether patients with embolic strokes of undetermined source (ESUS) have higher rates of elevated troponin than patients with noncardioembolic strokes. Methods and Results CAESAR (The Cornell Acute Stroke Academic Registry) prospectively enrolled all adults with acute stroke from 2011 to 2014. Two neurologists used standard definitions to retrospectively ascertain the etiology of stroke, with a third resolving disagreements. In this analysis we included patients with ESUS and, as controls, patients with small‐ and large‐artery strokes; only patients with a troponin measured within 24 hours of stroke onset were included. A troponin elevation was defined as a value exceeding our laboratorys upper limit (0.04 ng/mL) without a clinically recognized acute ST‐segment elevation myocardial infarction. Multiple logistic regression was used to evaluate the association between troponin elevation and ESUS after adjustment for demographics, stroke severity, insular infarction, and vascular risk factors. In a sensitivity analysis we excluded patients diagnosed with atrial fibrillation after discharge. Among 512 patients, 243 (47.5%) had ESUS, and 269 (52.5%) had small‐ or large‐artery stroke. In multivariable analysis an elevated troponin was independently associated with ESUS (odds ratio 3.3; 95% confidence interval 1.2, 8.8). This result was unchanged after excluding patients diagnosed with atrial fibrillation after discharge (odds ratio 3.4; 95% confidence interval 1.3, 9.1), and the association remained significant when troponin was considered a continuous variable (odds ratio for log[troponin], 1.4; 95% confidence interval 1.1, 1.7). Conclusions Elevations in cardiac troponin are more common in patients with ESUS than in those with noncardioembolic strokes.

Risk of Intracerebral Hemorrhage after Emergency Department Discharges for Hypertension

BACKGROUND Recent literature suggests that acute rises in blood pressure may precede intracerebral hemorrhage. We therefore hypothesized that patients discharged from the emergency department with hypertension face an increased risk of intracerebral hemorrhage in subsequent weeks. METHODS Using administrative claims data from California, New York, and Florida, we identified all patients discharged from the emergency department from 2005 to 2011 with a primary diagnosis of hypertension (ICD-9-CM codes 401-405). We excluded patients if they were hospitalized from the emergency department or had prior histories of cerebrovascular disease at the index visit with hypertension. We used the Mantel-Haenszel estimator for matched data to compare each patients odds of intracerebral hemorrhage during days 8-38 after emergency department discharge to the same patients odds during days 373-403 after discharge. This cohort-crossover design with a 1-week washout period enabled individual patients to serve as their own controls, thereby minimizing confounding bias. RESULTS Among the 552,569 patients discharged from the emergency department with a primary diagnosis of hypertension, 93 (.017%) were diagnosed with intracerebral hemorrhage during days 8-38 after discharge compared to 70 (.013%) during days 373-403 (odds ratio 1.33, 95% confidence interval .96-1.84). The odds of intracerebral hemorrhage were increased in certain subgroups of patients (≥60 years of age and those with secondary discharge diagnoses besides hypertension), but absolute risks were low in all subgroups. CONCLUSIONS Patients with emergency department discharges for hypertension do not face a substantially increased short-term risk of intracerebral hemorrhage after discharge.

Modeling the Impact of Interhospital Transfer Network Design on Stroke Outcomes in a Large City

Background and Purpose— We sought to model the effects of interhospital transfer network design on endovascular therapy eligibility and clinical outcomes of stroke because of large-vessel occlusion for the residents of a large city. Methods— We modeled 3 transfer network designs for New York City. In model A, patients were transferred from spoke hospitals to the closest hub hospitals with endovascular capabilities irrespective of hospital affiliation. In model B, which was considered the base case, patients were transferred to the closest affiliated hub hospitals. In model C, patients were transferred to the closest affiliated hospitals, and transfer times were adjusted to reflect full implementation of streamlined transfer protocols. Using Monte Carlo methods, we simulated the distributions of endovascular therapy eligibility and good functional outcomes (modified Rankin Scale score, 0–2) in these models. Results— In our models, 200 patients (interquartile range [IQR], 168–227) with a stroke amenable to endovascular therapy present to New York City spoke hospitals each year. Transferring patients to the closest hub hospital irrespective of affiliation (model A) resulted in 4 (IQR, 1–9) additional patients being eligible for endovascular therapy and an additional 1 (IQR, 0–2) patient achieving functional independence. Transferring patients only to affiliated hospitals while simulating full implementation of streamlined transfer protocols (model C) resulted in 17 (IQR, 3–41) additional patients being eligible for endovascular therapy and 3 (IQR, 1–8) additional patients achieving functional independence. Conclusions— Optimizing acute stroke transfer networks resulted in clinically small changes in population-level stroke outcomes in a dense, urban area.

Cryptogenic Stroke and Nonstenosing Intracranial Calcified Atherosclerosis

OBJECTIVE Because some cryptogenic strokes may result from large-artery atherosclerosis that goes unrecognized as it causes <50% luminal stenosis, we compared the prevalence of nonstenosing intracranial atherosclerotic plaques ipsilateral to cryptogenic cerebral infarcts versus the unaffected side using imaging biomarkers of calcium burden. METHODS In a prospective stroke registry, we identified patients with cerebral infarction limited to the territory of one internal carotid artery (ICA). We included patients with stroke of undetermined etiology and, as controls, patients with cardioembolic stroke. We used noncontrast computed tomography to measure calcification in both intracranial ICAs, including qualitative calcium scoring and quantitative scoring utilizing the Agatston-Janowitz (AJ) calcium scoring. Within subjects, the Wilcoxon signed-rank sum test for nonparametric paired data was used to compare the calcium burden in the ICA upstream of the infarction versus the ICA on the unaffected side. RESULTS We obtained 440 calcium measures from 110 ICAs in 55 patients. Among 34 patients with stroke of undetermined etiology, we found greater calcium in the ICA ipsilateral to the infarction (mean Modified Woodcock Visual Scale score, 6.7 ± 4.6) compared with the contralateral side (5.4 ± 4.1) (P = .005). Among 21 patients with cardioembolic stroke, we found no difference in calcium burden ipsilateral to the infarction (6.7 ± 5.9) versus the contralateral side (7.3 ± 6.3) (P = .13). The results were similar using quantitative calcium measurements, including the AJ calcium scores. CONCLUSION In patients with strokes of undetermined etiology, the burden of calcified intracranial large-artery plaque was associated with downstream cerebral infarction.

Risk of Stroke After the International Classification of Diseases-Ninth Revision Discharge Code Diagnosis of Hypertensive Encephalopathy

Background and Purpose— Although chronic hypertension is a well-established risk factor for stroke, little is known about stroke risk after hypertensive encephalopathy (HE), when neurologic sequelae of hypertension become evident. Therefore, we evaluated the risk of stroke after a diagnosis of HE. Methods— We identified all patients discharged from California, New York, and Florida emergency departments and acute care hospitals between 2005 and 2012 with a primary International Classification of Diseases, Ninth Edition, Clinical Modification discharge diagnosis of HE (437.2). Patients discharged with a primary diagnosis of seizure (345.x) served as negative controls, whereas patients with a primary diagnosis of transient ischemic attack (435.x) were positive controls. Our primary outcome was the composite of subsequent ischemic stroke or intracerebral hemorrhage. Kaplan–Meier survival statistics were used to calculate cumulative outcome rates, and Cox proportional hazard analysis was used to examine the association between index disease types and outcomes while adjusting for vascular risk factors. Results— We identified 8233 patients with HE, 191 091 with seizure, and 308 680 with transient ischemic attack. The 1-year cumulative rate of ischemic stroke or intracerebral hemorrhage after HE was 4.90% (95% confidence interval [CI], 4.45–5.40) when compared with 0.92% (95% CI, 0.88–0.97) after seizure and 4.49% (95% CI, 4.42–4.57) after transient ischemic attack. The risk of intracerebral hemorrhage was significantly elevated in those with HE (hazard ratio, 2.0; 95% CI, 1.7–2.5) but not in those with transient ischemic attack (hazard ratio, 1.0; 95% CI, 0.9–1.1), when compared with seizure patients. Conclusions— Patients discharged with a diagnosis of HE face a high risk of future cerebrovascular events, particularly intracerebral hemorrhage.