William Neil

Intravenous Thrombolysis in Ischemic Stroke Patients with Intracranial Neoplasms: Two Cases and a Literature Review

Based on exclusion criteria in the landmark NINDS-rtPA trial, current expert consensus guidelines preclude the use of intravenous recombinant tissue plasminogen activator (IV rtPA) in acute ischemic stroke (AIS) patients with intracranial neoplasm. There are only 3 published cases of administration of IV rtPA to AIS patients with intracranial neoplasms in the literature. Two of these published cases involved malignant brain parenchymal lesions discovered only after rtPA was inadvertently given, and one of these cases was associated with hemorrhage within the tumor. In this paper, we report two cases of administration of IV rtPA in AIS patients with intracranial neoplasms observed on neuroimaging prior to IV rtPA administration. In both cases, the tumor was outside of the brain parenchyma. The first case was an acoustic schwannoma and the second a falcine meningioma. Neither case was associated with intratumoral hemorrhage as of at least one week following IV rtPA treatment. More published cases are definitely warranted, but our experience with these two cases suggests that administration of IV rtPA to AIS patients in the presence of extraparenchymal brain tumors may not necessarily precipitate intra-tumoral bleeding and thereby worsen clinical outcomes.

Medico-legal aspects of using tissue plasminogen activator in acute ischemic stroke.

Opinion statementIntravenous alteplase or tissue plasminogen activator (tPA) has been the standard of care with proven efficacy for acute ischemic stroke for over a decade. Despite this, only a small fraction of potentially eligible stroke patients receive this medication. There seems to be a fear among practitioners of legal repercussions as a result of an increased risk of intracerebral hemorrhage due to tPA. This review of legal cases involving tPA will show that instead, physicians are often found liable as a result of not treating with tPA.

Neurologic Manifestations of Hypoglycemia

Unlike most other body tissues, the brain requires a continuous supply of glucose. It has very limited endogenous glycogen stores, and does not produce glucose intrinsically.1 Although it accounts for 2% of body weight, the brain utilizes 25% of the body’s glucose due to its high metabolic rate.2, 3 Evidence for the brains sole reliance on glucose came from obtaining a respiratory quotient of one after measuring differences between arterial and venous content of oxygen and carbon dioxide in blood traveling through the brain.4 In the past, neurons were thought to directly metabolize glucose, however, more recent studies suggest astrocytes may play an important role in glucose metabolism.5 Astrocytic foot processes surround brain capillaries, which deliver glucose to the brain. With this, they form the first cellular barrier for entering glucose.5 Astrocytes contain the non-insulin dependent GLUT1 transporter, as well as the insulin dependent GLUT4 transporter, suggesting a possible role for astrocytes in regulating and storing brain glucose in an insulin dependent and independent manner (see figure 1).6-8 In addition to glucose, the brain contains a very limited store of glycogen, (between 0.5 and 1.5 g, or about 0.1% of total brain weight). Unlike peripheral tissue, where glycogen is readily mobilized during hypoglycemia, the brain can only function normally for a limited duration. Glycogen content seems to fall in areas of highest brain metabolic rate, suggesting at least some, albeit limited role as fuel during hypoglycemia.7 Although the brain relies primarily on glucose during normal conditions, it can use ketone bodies during starvation. These ketone bodies cannot however meet all of the metabolic demands of the brain.9

Mail order pharmacy use and adherence to secondary prevention drugs among stroke patients

BACKGROUND AND PURPOSE Mail order pharmacies (MOP) are increasingly being used to deliver medications for chronic disease management. Their use is linked to similar or even greater medication adherence than local pharmacy (LP) use. We are unaware of any studies that have evaluated the association of mail order pharmacy use with drug adherence among stroke patients. METHODS We conducted cross-sectional analyses of patients discharged with ischemic stroke from 24 hospitals in a managed care network, who received a new anticoagulant, antiplatelet, anti-glycemic, antihypertensive, and/or lipid-lowering medication between January 1, 2007 and June 30, 2015. We defined good adherence as medication availability ≥80% of the time, and compared adherence between mail-order users (≥66% of refills by mail) and local pharmacy users (all refills in person). Relationship between delivery method and adherence was evaluated using multivariate regression models. RESULTS A total of 44,658 eligible patients refilled an index medication. Of these, 13,295 in the LP and 6801 in MOP groups met inclusion criteria. Patients in the MOP group were more likely to be white, and less likely to have hypertension, diabetes, and smoke tobacco. Continuous Medication Gap (CMG) adherence was 0.28 in the LP group and 0.11 in the MOP group (p < 0.001). At 90-days there were 893 hospital readmissions for the LP group and 375 for the MOP group for a rate of 0.07 vs 0.06 (p < 0.001). In the multivariable analysis, adherence was associated with MOP use, (OR 0.12, 95% CI 0.11-0.14) and decreased readmission at 90 days (OR 0.62, 95% CI 0.55-0.71). CONCLUSIONS Stroke patients who use MOP vs. LP are more likely to have good medication adherence. Future studies should examine the impact of mail-order pharmacy use on vascular risk marker control and events after stroke.

Emergency Care of Patients with Acute Ischemic Stroke in the Kaiser Permanente Southern California Integrated Health System.

CONTEXT Tissue plasminogen activator (tPA) is underutilized for treatment of acute ischemic stroke. OBJECTIVE To determine whether the probability of tPA administration for patients with ischemic stroke in an integrated health care system improved from 2009 to 2013, and to identify predictors of tPA administration. DESIGN Retrospective analysis of all ischemic stroke presentations to 14 Emergency Departments between 2009 and 2013. A generalized linear mixed-effects model identified patient and hospital predictors of tPA. MAIN OUTCOME MEASURES Primary outcome was tPA administration; secondary outcomes were door-to-imaging and door-to-needle times and tPA-related bleeding complications. RESULTS Of the 11,630 patients, 3.9% received tPA. The likelihood of tPA administration increased with presentation in 2012 and 2013 (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.26-2.43; and OR = 2.58; 95% CI = 1.90-3.51), female sex (OR = 1.27; 95% CI = 1.04-1.54), and ambulance arrival (OR = 2.17; 95% CI = 1.76-2.67), and decreased with prior stroke (OR = 0.47; 95% CI = 0.25-0.89) and increased age (OR = 0.98; 95% CI = 0.97-0.99). Likelihood varied by Medical Center (pseudo-intraclass correlation coefficient 13.5%). Among tPA-treated patients, median door-to-imaging time was 15 minutes (interquartile range, 9-23 minutes), and door-to-needle time was 73 minutes (interquartile range, 55-103 minutes). The rate of intracranial hemorrhage was 4.2% and 0.9% among tPA- and non-tPA treated patients (p < 0.001). CONCLUSION Acute ischemic stroke care improved over time in this integrated health system. Better understanding of differences in hospital performance will have important quality-improvement and policy implications.