Andrew Russman

The varicella zoster virus vasculopathies: Clinical, CSF, imaging, and virologic features

Background: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities. Methods: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both. Results: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. Conclusions: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers. GLOSSARY: EIA = enzyme immunoabsorbent assay; VZV = varicella zoster virus.

Outpatient cardiac telemetry detects a high rate of atrial fibrillation in cryptogenic stroke.

BACKGROUND The etiology of cerebral ischemia is undetermined in one-third of patients upon discharge. Occult paroxysmal atrial fibrillation (PAF) is considered a potential etiology. A high rate of PAF detection with 21-day mobile cardiac outpatient telemetry (MCOT) has been reported in two small studies. Optimal monitoring duration and factors predicting PAF have not been adequately defined. METHODS We performed a retrospective analysis on patients evaluated by MCOT monitoring within 6 months of a cryptogenic stroke or TIA. Multivariate analysis with survival regression methods was performed using baseline characteristics to determine predictive risk factors for detection of PAF. Kaplan-Meier estimates were computed for 21-day PAF rates. RESULTS We analyzed 156 records; PAF occurred in 27 of 156 (17.3%) patients during MCOT monitoring of up to 30 days. The rate of PAF detection significantly increased from 3.9% in the initial 48 h, to 9.2% at 7 days, 15.1% at 14 days, and 19.5% by 21 days (p<0.05). Female gender, premature atrial complex on ECG, increased left atrial diameter, reduced left ventricular ejection fraction and greater stroke severity were independent predictors of PAF detection on multivariate analysis with strongest correlation seen for premature atrial complex on ECG (HR 13.7, p=0.001). CONCLUSION MCOT frequently detects PAF in patients with cryptogenic stroke and TIA. Length of monitoring is strongly associated with detection of PAF, with an optimal monitoring period of at least 21 days. Of the predictors of PAF detection, the presence of premature atrial complexes on ECG held the strongest correlation with PAF.

Sildenafil Treatment of Subacute Ischemic Stroke: A Safety Study at 25-mg Daily for 2 Weeks

BACKGROUND In several animal studies of young and aged rats with ischemic stroke, treatment with sildenafil improved functional outcomes compared with placebo. We conducted a safety study of sildenafil (25 mg daily for 2 weeks) shortly after ischemic stroke onset. METHODS We recruited patients aged 18 to 80 years with ischemic stroke, National Institutes of Health stroke scale (NIHSS) score 2 to 21, between days 2 and 9 after symptom onset. Patients were treated with sildenafil for 2 weeks (25 mg daily). The primary outcome measure was the adverse occurrence of any of the following during the treatment period: stroke worsening, new stroke, myocardial infarction, vision loss, hearing loss, or death from any cause. Secondary outcome measures were NIHSS score, Barthel indices, and modified Rankin score at 90 days. RESULTS Twelve patients were recruited. Mean age was 57 years, 5 were female, and median NIHSS score at entry was 9.5 (range 2-20). The primary outcome measure occurred in one patient (sudden death). Another patient committed suicide 2 months after study entry (and 6 weeks after treatment with sildenafil had been completed). Among the 10 survivors, at 90 days, median NIHSS score was 2 (range 0-12), median Barthel index was 95 (range 15-100), and median modified Rankin score was 1.5 (range 0-5). CONCLUSIONS Sildenafil (25 mg daily for 2 weeks) appeared to be safe in this group of patients with mild to moderately severe stroke. Further studies of higher doses will be tested.

Development of a scoring system for atrial fibrillation in acute stroke and transient ischemic attack patients: The LADS scoring system☆

INTRODUCTION Detection of atrial fibrillation in patients presenting with ischemic stroke or transient ischemic attack (TIA) is important for the prevention of future events. We sought to develop a scoring system that would identify those patients most likely to have atrial fibrillation. METHODS Records from an inpatient stroke and TIA database and echocardiographic data were reviewed. Consecutive acute stroke and TIA patients over the age of 18 who were admitted during a two-year period were studied. Univariate and multivariable analyses were performed to identify variables associated with atrial fibrillation. Logistic regression analyses were used to develop a scoring system for atrial fibrillation. RESULTS 953 patient charts were reviewed; 145 patients (15%) had atrial fibrillation. In univariate and multivariate analyses, variables that were significantly associated with atrial fibrillation included left atrial diameter, age, and diagnosis of stroke. A history of smoking showed an inverse association. A 6-point scoring system based on these variables (with the acronym of LADS) was developed. A score of 4 or greater was associated with a sensitivity of 85.5% and a specificity of 53.1%. Approximately 47% of stroke and TIA patients would be excluded from further investigation using this score. CONCLUSIONS We describe a system of scoring that identifies acute stroke and TIA patients with a greater chance of having atrial fibrillation. An inverse relationship with smoking was found. Further prospective studies are required to determine the clinical utility and cost-effectiveness of this scoring system in clinical practice and to investigate the inverse relationship between smoking and atrial fibrillation in this population.

Brain Imaging Using Mobile CT: Current Status and Future Prospects

Computed tomography (CT) is an invaluable tool in the diagnosis of many clinical conditions. Several advancements in biomedical engineering have achieved increase in speed, improvements in low‐contrast detectability and image quality, and lower radiation. Portable or mobile CT constituted one such important advancement. It is especially useful in evaluating critically ill, intensive care unit patients by scanning them at bedside. A paradigm shift in utilization of mobile CT was its installation in ambulances for the management of acute stroke. Given the time sensitive nature of acute ischemic stroke, Mobile stroke units (MSU) were developed in Germany consisting of an ambulance equipped with a CT scanner, point of care laboratory system, along with teleradiological support. In a radical reconfiguration of stroke care, the MSU would bring the CT scanner to the stroke patient, without waiting for the patient at the emergency room. Two separate MSU projects in Saarland and Berlin demonstrated the safety and feasibility of this concept for prehospital stroke care, showing increased rate of intravenous thrombolysis and significant reduction in time to treatment compared to conventional care. MSU also improved the triage of patients to appropriate and specialized hospitals. Although multiple issues remain yet unanswered with the MSU concept including clinical outcome and cost‐effectiveness, the MSU venture is visionary and enables delivery of life‐saving and enhancing treatment for ischemic and hemorrhagic stroke. In this review, we discuss the development of mobile CT and its applications, with specific focus on its use in MSUs along with our institutions MSU experience.

Urine toxicology screening in an urban stroke and TIA population

Objective: We sought to determine the rate of urine toxicology screening, differences in testing, and outcomes among patients with stroke and TIA presenting to a tertiary care emergency department. Methods: In this retrospective cohort study, patients admitted with stroke or TIA to a single tertiary care stroke center between June 2005 and January 2007 were identified through a stroke database. Factors that predicted urine toxicology screening of patients and a positive test, and discharge outcomes of patients based on toxicology result were analyzed. Stroke severity, treatment with tissue plasminogen activator, discharge status, and stroke etiology were compared between toxicology positive and negative patients. Results: A total of 1,024 patients were identified: 704 with ischemic stroke, 133 with intracerebral hemorrhage, and 205 with TIA. Urine toxicology screening was performed in 420 patients (40%); 11% of these studies were positive for cocaine (19% younger than 50 years and 9% 50 years or older). Factors that significantly predicted the performance of a urine toxicology screen were younger age (<50 years) and black race (<0.001). Positive toxicology screens occurred in a broad range of patients. There were no significant differences in admission NIH Stroke Scale score, stroke etiology, and discharge status between toxicology-positive and -negative patients. Conclusions: In this study, patients with stroke and TIA who were young and black were more likely to have urine toxicology screening. Eleven percent of all tested patients (and 9% of patients 50 years or older) were positive for cocaine. To avoid disparities, we suggest that all stroke and TIA patients be tested.

A significant temporal and quantitative relationship exists between high-density lipoprotein levels and acute ischemic stroke presentation

BACKGROUND Reduced serum high-density lipoprotein (HDL-C) is an independent risk factor for ischemic stroke in elderly men. The temporal and quantitative relationships between HDL-C and acute ischemic stroke have not been defined. METHODS We identified patients with first ever acute ischemic stroke presenting to our hospital between 2003 and 2006. Patients with serum fasting lipid levels drawn within 24 h of admission and at least one follow-up visit with a neurologist in our hospital were included. Clinical and laboratory data before, immediately after, and several weeks after the index stroke were collected. RESULTS 191 patients were included (47% women, mean age 62 years). The mean time interval between pre-stroke lipid data and index stroke was 5.2 months; 50% of these patients were taking a statin medication. The mean time interval between index stroke and follow-up lipid testing was 2.6 months. Immediately after the index stroke, HDL-C levels decreased by 18% (p<0.001) relative to pre-stroke levels. This phenomenon was independent of stroke severity, and was blunted among patients with a prior history of myocardial infarction (p<0.01). HDL-C levels increased to pre-stroke levels within 3 months post-stroke. CONCLUSIONS HDL-C levels decrease significantly at the time of acute ischemic stroke. Prior history of myocardial infarction diminishes HDL-C depression at the time of stroke. HDL-C may be an acute phase reactant or nascent biomarker of acute stroke susceptibility. Further prospective studies are needed.

Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis

Objective: To compare the times to evaluation and thrombolytic treatment of patients treated with a telemedicine-enabled mobile stroke treatment unit (MSTU) vs those among patients brought to the emergency department (ED) via a traditional ambulance. Methods: We implemented a MSTU with telemedicine at our institution starting July 18, 2014. A vascular neurologist evaluated each patient via telemedicine and a neuroradiologist and vascular neurologist remotely assessed images obtained by the MSTU CT. Data were entered in a prospective registry. The evaluation and treatment of the first 100 MSTU patients (July 18, 2014–November 1, 2014) was compared to a control group of 53 patients brought to the ED via a traditional ambulance in 2014. Times were expressed as medians with their interquartile ranges. Results: Patient and stroke severity characteristics were similar between 100 MSTU and 53 ED control patients (initial NIH Stroke Scale score 6 vs 7, p = 0.679). There was a significant reduction of median alarm-to-CT scan completion times (33 minutes MSTU vs 56 minutes controls, p < 0.0001), median alarm-to-thrombolysis times (55.5 minutes MSTU vs 94 minutes controls, p < 0.0001), median door-to-thrombolysis times (31.5 minutes MSTU vs 58 minutes controls, p = 0.0012), and symptom-onset-to-thrombolysis times (97 minutes MSTU vs 122.5 minutes controls, p = 0.0485). Sixteen patients evaluated on MSTU received thrombolysis, 25% of whom received it within 60 minutes of symptom onset. Conclusion: Compared with the traditional ambulance model, telemedicine-enabled ambulance-based thrombolysis resulted in significantly decreased time to imaging and treatment.

Initial Experience With High-Risk Patients Excluded From Clinical Trials: Safety of Short-Term Anticoagulation After Left Atrial Appendage Closure Device.

Background—The implantation of left atrial appendage closure device (WATCHMAN, Boston Scientific, Natick, MA) is an alternative option to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation. Patients require short-term OAC after implantation to avoid device thrombosis. The 2 clinical trials that assessed this device excluded patients thought not to be candidates for OAC. As such, little is known about the safety of this strategy in patients with previous major bleeding events. Methods and Results—All 20 consecutive patients with history of spontaneous major bleeding while on OAC who had subsequently undergone WATCHMAN device implantation at our institution were included. A newly conceived multidisciplinary Atrial Fibrillation Stroke Prevention Center evaluated patients for candidacy for device implantation and subsequent antithrombotic therapy. The primary outcome was spontaneous major bleeding while receiving short-term postprocedural OAC. Median CHA2DS2-VASc and HAS-BLED scores were 5 (quartiles 5–6) and 5 (quartiles 4–5), respectively. Previous major bleeding events were major gastrointestinal bleeding, intracranial bleeding, spontaneous hemopericardium with cardiac tamponade, and hemarthrosis in 11, 7, 1, and 1 patients, respectively. None of the patients had spontaneous major bleeding during the course of OAC after device implantation. In 1 patient, OAC was discontinued after 40 days because of mechanical fall with head trauma resulting in subdural hematoma with no associated neurological deficits; this was managed conservatively. Conclusions—With careful multidisciplinary evaluation, a short course of OAC after WATCHMAN device implantation in patients with previous spontaneous major bleeding events is associated with low risk of recurrent spontaneous major bleeding.

Normative Performance on the Balance Error Scoring System by Youth, High School, and Collegiate Athletes

CONTEXT   Annually, more than 1 million youth athletes in the United States receive or are suspected of receiving a concussion. The Balance Error Scoring System (BESS) is the most commonly used clinical balance evaluation designed to provide a better understanding of the motor-control processes of individuals with concussion. Despite the widespread use of the BESS, a fundamental gap exists in applying this tool to young athletes, as normative values are lacking for this population. OBJECTIVE   To determine age- and sex-specific normative values for the BESS in youth, high school, and collegiate athletes. DESIGN   Cross-sectional study. SETTING   Local youth sport organizations, high schools, and colleges. PATIENTS OR OTHER PARTICIPANTS   Student-athletes (N = 6762) completed preseason baseline concussion testing as part of a comprehensive concussion-management program. Groups were youth males aged 5 to 13 years (n = 360), high school males aged 14 to 18 years (n = 3743), collegiate males aged 19 to 23 years (n = 497), youth females aged 5 to 13 years (n = 246), high school females aged 14 to 18 years (n = 1673), and collegiate females aged 19 to 23 years (n = 243). MAIN OUTCOME MEASURE(S)   Errors according to the BESS specifications. RESULTS   Performance on the BESS was worse ( P < .01) in youth athletes than in high school and collegiate athletes. In the youth and high school cohorts, females exhibited better scores than males ( P < .05). Sex was not a factor for collegiate athletes. Data from the youth cohort were further subdivided into 4-year bins to evaluate potential motor-development differences. The error count was highest for 5- to 9-year-old males and decreased with age. CONCLUSIONS   Performance on the BESS depended on sex and age, particularly in youth athletes. These sex- and age-specific normative values provide a reference to facilitate and unify clinical decision making across multiple providers caring for youth athletes with concussions.