Transferring Patients with Intracerebral Hemorrhage Does Not Increase In-Hospital Mortality.

INTRODUCTION: Comprehensive stroke centers (CSCs) accept transferred patients from referring hospitals in a given regional area. The transfer process itself has not been studied as a potential factor that may impact outcome. We compared in-hospital mortality and severe disability or death at CSCs between transferred and directly admitted intracerebral hemorrhage (ICH) patients of matched severity. MATERIALS AND METHODS: We retrospectively reviewed all primary ICH patients from a prospectively-collected stroke registry and electronic medical records, at two tertiary care sites. Patients meeting inclusion criteria were divided into two groups: patients transferred in for a higher level of care and direct presenters. We used propensity scores (PS) to match 175 transfer patients to 175 direct presenters. These patients were taken from a pool of 530 eligible patients, 291 (54.9%) of whom were transferred in for a higher level of care. Severe disability or death was defined as a modified Rankin Scale (mRS) sore of 4-6. Mortality and morbidity were compared between the 2 groups using Pearson chi-squared test and Student t test. We fit logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between transfer status and in-hospital mortality and severe disability or death in full and PS-matched patients. RESULTS: There were no significant differences in the PS-matched transfer and direct presentation groups. Patients transferred to a regional center were not at higher odds of in-hospital mortality (OR: 0.93, 95% CI: 0.50-1.71) and severe disability or death (OR: 0.77, 95% CI: 0.39-1.50), than direct presenters, even after adjustment for PS, age, baseline NIHSS score, and glucose on admission. CONCLUSION: Our observation suggests that transfer patients of similar disease burden are not at higher risk of in-hospital mortality than direct presenters.

Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke.

OBJECTIVE: It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) in patients with wake-up stroke (WUS). METHODS: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) ≤25, and selected only on the appearance of noncontrast computed tomography (ie, over one-third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score. RESULTS: Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2-24), and received thrombolysis at a mean time of 10.3 ± 2.6 LSN and 2.6 ± 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up). INTERPRETATION: Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211-218.

Acute splenic responses in patients with ischemic stroke and intracerebral hemorrhage.

Animal models provide evidence of spleen mediated post-stroke activation of the peripheral immune system. Translation of these findings to stroke patients requires estimation of pre-stroke spleen volume along with quantification of its day-to-day variation. We enrolled a cohort of 158 healthy volunteers and measured their spleen volume over the course of five consecutive days. We also enrolled a concurrent cohort of 158 stroke patients, measured initial spleen volume within 24 h of stroke symptom onset followed by daily assessments. Blood samples for cytokine analysis were collected from a subset of patients. Using data from healthy volunteers, we fit longitudinal quantile regression models to construct gender and body surface area based normograms of spleen volume. We quantified day-to-day variation and defined splenic contraction. Based on our criteria, approximately 40% of stroke patients experienced substantial post-stroke reduction in splenic volume. African Americans, older patients, and patients with past history of stroke have significantly higher odds of post-stroke splenic contraction. All measured cytokine levels were elevated in patients with splenic contraction, with significant differences for interferon gamma, interleukin 6, 10, 12, and 13. Our work provides reference standards for further work, validation of pre-clinical findings, and characterization of patients with post-stroke splenic contraction.

Resource Utilization for Patients with Intracerebral Hemorrhage Transferred to a Comprehensive Stroke Center.

BACKGROUND: As a comprehensive stroke center (CSC), we accept transfer patients with intracerebral hemorrhage (ICH) in our region. CSC guidelines mandate receipt of patients with ICH for higher level of care. We determined resource utilization of patients accepted from outside hospitals compared with patients directly arriving to our center. METHODS: From our stroke registry, we compared patients with primary ICH transferred to those directly arriving to our CSC from March 2011-March 2012. We compared the proportion of patients who utilized at least one of these resources: neurointensive care unit (NICU), neurosurgical intervention, or clinical trial enrollment. RESULTS: Among the 362 patients, 210 (58%) were transfers. Transferred patients were older, had higher median Glasgow Coma Scale scores, and lower National Institutes of Health Stroke Scale scores than directly admitted patients. Transfers had smaller median ICH volumes (20.5 cc versus 15.2 cc; P = .04) and lower ICH scores (2.1 ± 1.4 versus 1.6 ± 1.3; P < .01). A smaller proportion of transfers utilized CSC-specific resources compared with direct admits (P = .02). Fewer transferred patients required neurosurgical intervention or were enrolled in trials. No significant difference was found in the proportion of patients who used NICU resources, although transferred patients had a significantly lower length of stay in the NICU. Average hospital stay costs were less for transferred patients than for direct admits. CONCLUSIONS: Patients with ICH transferred to our CSC underwent fewer neurosurgical procedures and had a shorter stay in the NICU. These results were reflected in the lower per-patient costs in the transferred group. Our results raise the need to analyze cost-benefits and resource utilization of transferring patients with milder ICH.

Prehospital utility of rapid stroke evaluation using in-ambulance telemedicine: a pilot feasibility study.

BACKGROUND AND PURPOSE: Prehospital evaluation using telemedicine may accelerate acute stroke treatment with tissue-type plasminogen activator. We explored the feasibility and reliability of using telemedicine in the field and ambulance to help evaluate acute stroke patients. METHODS: Ten unique, scripted stroke scenarios, each conducted 4 times, were portrayed by trained actors retrieved and transported by Houston Fire Department emergency medical technicians to our stroke center. The vascular neurologists performed remote assessments in real time, obtaining clinical data points and National Institutes of Health (NIH) Stroke Scale, using the In-Touch RP-Xpress telemedicine device. Each scripted scenario was recorded for a subsequent evaluation by a second blinded vascular neurologist. Study feasibility was defined by the ability to conduct 80% of the sessions without major technological limitations. Reliability of video interpretation was defined by a 90% concordance between the data derived during the real-time sessions and those from the scripted scenarios. RESULTS: In 34 of 40 (85%) scenarios, the teleconsultation was conducted without major technical complication. The absolute agreement for intraclass correlation was 0.997 (95% confidence interval, 0.992-0.999) for the NIH Stroke Scale obtained during the real-time sessions and 0.993 (95% confidence interval, 0.975-0.999) for the recorded sessions. Inter-rater agreement using κ-statistics showed that for live-raters, 10 of 15 items on the NIH Stroke Scale showed excellent agreement and 5 of 15 showed moderate agreement. Matching of real-time assessments occurred for 88% (30/34) of NIH Stroke Scale scores by ±2 points and 96% of the clinical information. CONCLUSIONS: Mobile telemedicine is reliable and feasible in assessing actors simulating acute stroke in the prehospital setting.

Optimizing prediction scores for poor outcome after intra-arterial therapy in anterior circulation acute ischemic stroke.

BACKGROUND AND PURPOSE: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. METHODS: Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University. RESULTS: A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. CONCLUSIONS: The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Changes in spleen size in patients with acute ischemic stroke: a pilot observational study.

BACKGROUND: In animal models, the spleen contracts after acute ischemic stroke, followed by release of inflammatory cells leading to secondary brain injury. AIMS: We aim to characterize splenic responses in patients with acute ischemic stroke. METHODS: In this prospective observational study, we measured daily spleen sizes with abdominal ultrasound in 30 patients with suspected acute ischemic stroke. Splenic ultrasounds were also performed in 20 healthy individuals. RESULTS: A generalized estimating equation, longitudinal regression model for adjusted spleen measurements showed the difference between baseline spleen volume (within six-hours of stroke onset) and the volume at the last measured time point (up to seven-days) to be statistically significant (volume difference of 51·9 cm(3) , P = 0·04). Healthy controls had significantly smaller day-to-day variations; the maximum observed difference in mean spleen volume between any two time points was 9·5 cm(3) , with the average change over the period of observation being 1·24 cm(3) . A statistically significant negative association was also observed between the pattern of change of total white blood cell count and spleen volume (P = 0·01). An analysis of individual cases demonstrated possible associations between daily spleen volume changes and clinical course. CONCLUSIONS: We hypothesize that the spleen may initially contract after ischemic stroke followed by a re-expansion and that it contributes to ischemic brain injury mediated via cellular components. Characterization of the splenic response after stroke and its contribution to cerebral ischemic injury has the potential to provide new opportunities for the development of novel stroke therapies.

Hyperkyphotic posture and risk of injurious falls in older persons: the Rancho Bernardo Study.

OBJECTIVE: Falls among older adults can have serious physical and emotional consequences, ultimately leading to a loss of independence. Improved identification of those at risk for falls could lead to effective interventions. Because hyperkyphotic posture is associated with impaired physical functioning, we hypothesized that kyphosis may also be associated with falls. METHODS: Participants were 1883 older adults from the Rancho Bernardo Study. Between 1988 and 1991, kyphosis was measured using a system of 1.7-cm blocks placed under the participants' heads if they were unable to lie flat without neck hyperextension. Data on falls including injurious falls, demographics, health, and habits were obtained from a self-administered questionnaire completed at the same visit. RESULTS: Hyperkyphosis was defined as requiring the use of > or = 1 blocks (n = 595, 31.6%). In this cohort, men were more likely to be hyperkyphotic than were women (p <.0001). Of those who fell, 36.3% were hyperkyphotic, versus 30.2% among those who did not fall (p =.015). Those who fell were older, more likely to be women, had lower body mass index, did not exercise, did not drink alcohol, and had poor self-reported physical and emotional health. In age- and sex-adjusted models, those with hyperkyphosis were at 1.38-fold increased odds of experiencing an injurious fall (95% confidence interval [CI], 1.05-1.91; p =.02) that increased to 1.48 using a cutoff of > or = 2 blocks versus < or = 1 blocks (95% CI, 1.10-2.00; p =.01). Although women were more likely to fall, after adjustment for possible confounders, men with moderate hyperkyphosis were at greatest fall risk. CONCLUSIONS: Moderate hyperkyphotic posture may signify an easily identifiable independent risk factor for injurious falls in older men, with the association being less pronounced in older women.

Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses.

INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.