Faculty Bibliography

BACKGROUND: Ischemic arterial strokes of the ophthalmic artery and its branches and posterior cerebral artery are common causes of visual disability. Etiologies of stroke affecting the retina, optic nerve, optic radiation, and visual cortex overlap with other types of ischemic strokes. Stenosis of the internal carotid is the most common cause of central retinal artery occlusion (CRAO). One-fourth of patients with CRAO have cerebral strokes. We report recent developments in the acute treatment and secondary prevention of ischemic stroke of relevance to clinicians who encounter patients with acute vision loss. EVIDENCE ACQUISITION: A search of Pubmed and practice guidelines over the past 5 years was performed, with a focus on significant changes in treatment and prevention of ischemic stroke. RESULTS: Recent randomized controlled trials provide Level I evidence for the use of endovascular therapy with current stent retriever devices for patients with large vessel anterior circulation occlusions within 6 hours of presentation. Number needed to treat to achieve one additional patient with an independent functional outcome was in the range of 3-7, and benefit was additive to that of intravenous tissue plasminogen activator alone. Paroxysmal atrial fibrillation (AF) is a major cause of cryptogenic stroke with incidence expected to rise with the aging population. Since 2014, prolonged 30-day cardiac monitoring has been recommended as a part of transient ischemic attack and stroke workup in patients with cryptogenic stroke. Even longer term monitoring of 6 months to 1 year with external and implantable loop recorders improves rates of diagnosing AF. First available in 2010, the novel anticoagulants-dabigatran, apixaban, rivaroxaban, and edoxaban-have been compared with warfarin in the prevention of stroke in patients with nonvalvular AF. Apixaban demonstrated superiority in safety and efficacy, with the novel anticoagulants as a group having favorable risk-benefit profile at higher dosages compared with standard warfarin therapy. CONCLUSIONS: Endovascular therapy is now standard of care for eligible patients with anterior large vessel occlusions. Prolonged cardiac monitoring is recommended for patients with cryptogenic stroke. The novel anticoagulants are an alternative to warfarin in patients with AF.

INTRODUCTION: Intravenous (IV) tissue plasminogen activator (tPA) is contraindicated in therapeutically anti-coagulated patients. Such patients may be considered for endovascular intervention. However, there are limited data on its safety. PATIENTS AND METHODS: We performed a multicenter retrospective study of patients undergoing endovascular intervention for acute ischemic stroke while on therapeutic anticoagulation. We compared the observed rate of National Institute of Neurological Disorders and Stroke defined symptomatic intracerebral hemorrhage (sICH) with risk-adjusted historical control rates of sICH after IV tPA using weighted averages of the hemorrhage after thrombolysis (HAT) and Multicenter Stroke Survey (MSS) prediction scores. We also performed a metaanalysis of studies assessing risk of sICH with endovascular intervention in patients on anticoagulation. RESULTS AND DISCUSSION: Of 94 cases, mean age was 73 years and median National Institutes of Health Stroke Scale was 19. Anticoagulation consisted of warfarin (n = 51), dabigatran (n = 6), rivaroxaban (n = 13), apixaban (n = 1), IV heparin (n = 19), low molecular weight heparin (n = 3), and combined warfarin and IV heparin (n = 3). sICH was seen in 7 patients (7%, 95% confidence interval 4-15), all on warfarin. Predicted sICH rates for the cohort based on HAT and MSS scoring were 12% and 7%, respectively. Meta-analysis of 6 studies showed no significant difference in sICH between patients undergoing endovascular intervention on anticoagulation and comparator groups. CONCLUSIONS: Endovascular intervention in subjects on therapeutic anticoagulation appears reasonably safe, with a sICH rate similar to patients not on anticoagulation receiving IV tPA.

PURPOSE: Infarction of the corpus callosum is rare, and other conditions can cause magnetic resonance imaging (MRI) restricted diffusion in the callosum, leading to diagnostic uncertainty. We sought to characterize the etiology of lesions with diffusion restriction in the corpus callosum. METHODS: Callosal lesions with restricted diffusion were identified at our institution between January 2000 and December 2010. Radiographic and clinical data were reviewed to determine whether the lesion was vascular and if so, to identify the underlying mechanism. RESULTS: A total of 174 cases were reviewed in depth; 47 % were vascular and 53 % were nonvascular. Among vascular cases, atypical mechanisms of stroke (e.g., vasculitis/vasculopathy, hypercoagulable state) were most common (37 %), followed by cardioembolism (28 %). Vascular splenial lesions in particular were likely due to atypical causes of stroke. The most common nonvascular etiologies were trauma (44 %), tumor (22 %), and demyelination (15 %). Vascular lesions were more common in older, non-Caucasian patients with vascular risk factors. Nonvascular lesions were more likely to be found in association with T2-hyperintense cortical lesions, focal intraparenchymal enhancement, or edema/mass effect on MRI. CONCLUSIONS: More than half of lesions with diffusion restriction in the corpus callosum are due to a nonvascular cause. Clinical and radiographic characteristics can help distinguish vascular from nonvascular lesions in the corpus callosum. Nonvascular lesions are more likely to be seen in younger patients without vascular risk factors and are more often accompanied by enhancement and edema. Vascular lesions are most commonly due to atypical stroke etiologies, and these patients may require additional diagnostic testing.

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.

Introduction Patients with intracerebral hemorrhage (ICH) frequently present with hypertension. It is unclear whether this is due to preexisting hypertension (prHTN) causing the bleed, an effect of the bleed, or both. Methods We retrospectively analyzed a single-institution cohort of ICH patients presenting between 2013 and 2016. Data included home antihypertensive use; aSBP; TTE, and EKG and imaging results; and nicardipine administration. The primary objective was to assess the relationship between prHTN and aSBP, while the secondary objectives were to assess the relationship between prHTN, imaging and acute antihypertensive requirements. Results 112 ICH patients met inclusion criteria. In our assessment for prHTN, we found that 46% of patients were on antihypertensives, 16% had LVH on EKG, and 15% had LVH on TTE. There was a significant relationship between LVH on TTE and LVH on EKG (p<0.001), but not between home antihypertensive use and presence of LVH using either modality. aSBP was higher for all patients with markers of pHTN, but this was only significant for patients with LVH on TTE (181mmHg, IQR 153-214 vs. 152mmHg, IQR 137-169, p < 0.001) and patients with LVH on EKG (195 mm Hg, IQR 155-216 vs. 147 mm Hg, IQR 129- 163, p<0.001). All patients with markers of prHTN were more likely to require nicardipine, but this was only significant for patients with LVH on TTE (94% vs. 64%, p=0.016) and patients with LVH on EKG (83% vs. 52%, p=0.018). All patients with markers of prHTN were more likely to have deep bleeds (p=0.017 for patients with LVH on EKG vs. those without LVH on EKG). There was no relationship between any markers of prHTN and the presence of a spot sign. Conclusions In patients with ICH, prHTN is related to higher aSBP, deep bleed location, and increased acute antihypertensive requirements

BACKGROUND AND PURPOSE: Infections are common after intracerebral hemorrhage, but little is known about the risk of serious infection requiring readmission after hospital discharge. METHODS: To determine if infections are prevalent in patients readmitted within 30 days of discharge, we performed a retrospective cohort study of patients discharged from nonfederal acute care hospitals in California with a primary diagnosis of intracerebral hemorrhage between 2006 and 2010. We excluded patients who died during the index admission, were discharged against medical advice, or were not California residents. Our main outcome was 30-day unplanned readmission with primary infection-related International Classification of Diseases, Ninth Revision, Clinical Modification code. RESULTS: There were 24 540 index intracerebral hemorrhage visits from 2006 to 2010. Unplanned readmissions occurred in 14.5% (n=3550) of index patients. Of 3550 readmissions, 777 (22%) had an infection-related primary diagnosis code. When evaluating primary and all secondary diagnosis codes, infection was associated with 1826 (51%) of readmissions. Other common diagnoses associated with readmission included stroke-related codes (n=840, 23.7%) and aspiration pneumonitis (n=154, 4.3%). The most common infection-related primary diagnosis codes were septicemia (n=420, 11.8%), pneumonia (n=124, 3.5%), urinary tract infection (n=141, 4.0%), and gastrointestinal infection (n=42, 1.2%). Patients with a primary infection-related International Classification of Diseases, Ninth Revision, Clinical Modification code on readmission had higher in-hospital mortality compared with other types of readmission (15.6% versus 8.0%, P<0.001). After controlling for other predictors of mortality, primary infection-related readmissions remained associated with in-hospital mortality (relative risk, 1.7; 95% confidence interval, 1.3-2.2). CONCLUSIONS: Infections are associated with a majority of 30-day readmissions after intracerebral hemorrhage and increased mortality. Efforts should be made to reduce infection-related complications after hospital discharge.

Introduction Infections are common inpatient complications after intracerebral hemorrhage (ICH), but little is known about risk of infection after hospital discharge. Methods We performed a retrospective cohort study of patients discharged from non-federal acute-care hospitals in California with a primary diagnosis of ICH between 2006 and 2010. ICH was defined as a primary ICD-9CM discharge diagnosis code of 431. Only the first eligible ICH admission was included for each patient. Exclusion criteria were discharge against medical advice, in-hospital death, and non-California residency. After discharge from index admission, we assessed the proportion of readmissions to an acute-care hospital within 30 days that were related to infection. Clinical Classification Software (CCS) categorization of ICD-9CM codes was utilized for etiology of readmission. Inter-hospital transfers and readmission for likely planned procedures (craniotomy, embolization) were not included. Log-binomial regression was used to assess relationship between baseline characteristics and readmission mortality. Results There were 24,540 index ICH visits from 2006 to 2010. Unplanned readmissions occurred in 14.8% (n=3,269) of index patients. Of the 3,269 revisits, 934 (26%) had an infection-related primary diagnosis code. When evaluating all available revisit diagnosis codes, infection was associated with 1,945 (54%) of readmissions. Other common primary causes for readmission included stroke-related codes (n=894, 24.6%) and complications of medical/surgical care (n=92, 2.5%). The most common infection-related primary diagnosis codes were septicemia (n=422, 11.6%), respiratory infections/aspiration (n=292, 8.0%), urinary tract infection (n=141, 3.9%), and gastrointestinal infection (n=90, 2.5%). Patients with primary infection-related readmissions had higher in-hospital mortality compared to other types of readmission (15.7% vs. 7.7%, p< 0.001). After controlling for other predictors of mortality, primary infection-related readmissions remained associated with in-hospital mortality (RR=1.5, 95% CI 1.2-1.8). Conclusions Readmission for infection after ICH is common and associated with in-hospital death. Efforts should be made to identify ways to reduce infection-related complications in ICH patients after hospital discharge

RATIONALE: Stroke and vascular risk factors disproportionately affect minority populations, with Blacks and Hispanics experiencing a 2.5- and 2.0-fold greater risk compared with whites, respectively. Patients with transient ischemic attacks and mild, nondisabling strokes tend to have short hospital stays, rapid discharges, and inaccurate perceptions of vascular risk. AIM: The primary aim of the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial is to evaluate the efficacy of a novel community health worker-based multilevel discharge intervention vs. standard discharge care on vascular risk reduction among racially/ethnically diverse transient ischemic attack/mild stroke patients at one-year postdischarge. We hypothesize that those randomized to the discharge intervention will have reduced modifiable vascular risk factors as determined by systolic blood pressure compared with those receiving usual care. SAMPLE SIZE ESTIMATES: Given 300 subjects per group and alpha of 0.05, the power to detect a 6 mmHg reduction in systolic blood pressure is 89%. DESIGN: DESERVE trial is a prospective, randomized, multicenter clinical trial of a novel discharge behavioral intervention. Patients with transient ischemic attack/mild stroke are randomized during hospitalization or emergency room visit to intervention or usual care. Intervention begins prior to discharge and continues postdischarge. STUDY OUTCOMES: The primary outcome is difference in systolic blood pressure reduction between groups at 12 months. Secondary outcomes include between-group differences in change in glycated hemoglobin, smoking rates, medication adherence, and recurrent stroke/transient ischemic attack at 12 months. DISCUSSION: DESERVE will evaluate whether a novel discharge education strategy leads to improved risk factor control in a racially diverse population.

OPINION STATEMENT: Neurologic injury is a common complication of major cardiovascular procedures including coronary artery bypass graft (CABG) surgery, coronary valve replacement, and aortic aneurysm surgery. However, despite ongoing research in the field of neuroprotection, there are currently few pharmacologic and interventional options to effectively protect the brain and spinal cord in the postoperative period. CSF drainage after aortic surgery currently stands as the only neuroprotective intervention that has been consistently shown to protect the spinal cord from ischemic injury, leading to significantly fewer patients with paraplegia and paraparesis. There is promising but conflicting evidence about the potential benefits of agents such as dexmedetomidine, lidocaine, magnesium, and erythropoietin in preventing postoperative stroke and cognitive dysfunction. Postoperative hypothermia has also been studied in preventing neurologic injury after cardiopulmonary bypass. With the rate of cardiovascular surgeries increasing yearly, further investigations are needed to validate many of these therapies and discover new ways to protect the brain and spinal cord from intraoperative and postoperative injuries in this high-risk population.