Patients with Low National Institutes of Health Stroke Scale Scores Have Longer Door-to-Needle Times: Analysis of a Telestroke Network.

BACKGROUND: The benefits of intravenous tissue-type plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) are time dependent. Because emergency rooms quickly initiate a stroke alert with more severe symptoms, we hypothesized that patients with lower National Institutes of Health Stroke Scale (NIHSS) scores, indicating a less severe stroke, would have longer door-to-needle (DTN) times compared to patients with higher NIHSS scores. METHODS: Data obtained from the 19-hospital Providence Stroke Registry were used to identify AIS patients who received IV-tPA within 4.5 hours of last-known-well. NIHSS scores were obtained prior to tPA administration at the time of emergency department presentation and categorized as low-NIHSS (score = 0-5) or high-NIHSS (score = 6-42) strokes. Median DTN times were collected for both groups as the primary outcome variable. Linear mixed-effects regression models were used to assess the effect of NIHSS scores on DTN and its 2 components: door-to-CT (DCT) and CT-to-needle (CTN) times. RESULTS: We identified 692 AIS patients who received IV-tPA within 4.5 hours of last-known-well, with 198 patients presenting with low-NIHSS strokes and 494 patients with high-NIHSS strokes. In multivariable analysis, median DTN time was estimated to be 18% higher for low-NIHSS strokes than high-NIHSS strokes after adjusting for covariates (P < .001). Median DCT times were also higher for low-NIHSS (19 minutes) compared to high-NIHSS (11 minutes) strokes after adjusting for covariates (P < .001), whereas CTN times were unchanged (P = .055). CONCLUSION: In AIS patients receiving IV-tPA in a telestroke network, lower NIHSS scores were associated with longer DTN and DCT times.

The cost-effectiveness of telestroke in the Pacific Northwest region of the USA.

INTRODUCTION: Using real-world data from the Providence Oregon Telestroke Network, we examined the cost-effectiveness of telestroke from both the spoke and hub perspectives by level of financial responsibility for these costs and by patient stroke severity. METHODS: We constructed a decision analytic model using patient-level clinical and financial data from before and after telestroke implementation. Effectiveness was measured as quality-adjusted life years (QALYs) and was combined with cost per patient outcomes to calculate incremental cost effectiveness ratios (ICERs). Outcomes were generated (a) overall; (b) by stroke severity, via the National Institute of Health Stroke Scale (NIHSS) at time of arrival, defined as low (<5), medium (5-14) and high (>15); and (c) by percentage of implementation costs paid by spokes (0%, 50%, 100%). RESULTS: Data for 864 patients, 98 pre- and 766 post-implementation, were used to parameterize our model. From the spoke perspective, telestroke had ICERs of US$1322/QALY, US$25,991/QALY and US$50,687/QALY when responsible for 0%, 50%, and 100% of these costs, respectively. Overall, the ICER ranged from US$22,363/QALY to US$71,703/QALY from the hub perspective. CONCLUSIONS: Our results support previous models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective for the spokes if spokes paid for more than half of implementation costs.

An uncommon cause of transient neurological dysfunction.

Transient neurological dysfunction may be associated with uncommon disorders and should prompt consideration of a broad differential diagnosis when assessing patients with episodic symptoms. The most common causes of transient neurological dysfunction include transient ischemic attack (TIA), seizure disorder, and migraine and its variants. However, underlying unusual pathophysiological processes such as brain tumors can also cause transient neurological dysfunction. Here we present a case of a 68-year-old male with oligodendroglial gliomatosis cerebri (OGC) who presented with TIA-like symptoms. Brain magnetic resonance imaging revealed multiple diffuse T2 hyperintensities within the white and gray matter. Magnetic resonance spectroscopy was suggestive of gliomatosis cerebri and was particularly helpful in this case. The diagnosis of OGC was confirmed by histopathology and molecular genetic studies on brain biopsy tissue. In this report, we discuss the clinical and radiological characteristics of OGC and highlight the unusual presentation of this case.

Incorporating diffusion-weighted magnetic resonance imaging into an observation unit transient ischemic attack pathway: a prospective study.

BACKGROUND AND PURPOSE: National guidelines advocate for early, aggressive transient ischemic attack (TIA) evaluations and recommend diffusion-weighted magnetic resonance imaging (MRI) for brain imaging. The purpose of this study is to examine clinician compliance, the yield of MRI, and patient-centered clinical outcomes following implementation of an emergency department observation unit (EDOU) clinical pathway incorporating routine MRI into the acute evaluation of patients with TIA. METHODS: This is a prospective observational study of patients with TIA admitted from the ED. Patients with low-risk TIA were transferred to an EDOU for diagnostic testing including MRI; high-risk patients were directed to hospital admission. Clinical variables, diagnostic tests, and treatment were recorded for all patients. The primary clinical outcome was the rate of stroke or recurrent TIA, determined through telephone follow-up and medical record review at 7 and 30 days. RESULTS: A total of 116 patients with TIA were enrolled. In all, 92 (79.3%) patients were transferred to the EDOU, of whom 69 (59.5%) were discharged without hospitalization. Compliance with the EDOU pathway was 83 (91.2%) of 92. Magnetic resonance imaging demonstrated acute infarct in 16 (15.7%) of 102 patients. Stroke (n = 2) or TIA (n = 3) occurred in 5 patients with TIA (4.3%, 95% confidence interval: 1.6%-10.0%) within 30 days; no strokes occurred after discharge. CONCLUSIONS: Implementation of a TIA clinical pathway incorporating MRI effectively encouraged guideline-compliant diagnostic testing; however, patient-important outcomes appear similar to diagnostic protocols without routine MRI. Further study is needed to assess the benefits and costs associated with routinely incorporating MRI into TIA evaluation.

Medicolegal considerations with intravenous tissue plasminogen activator in stroke: a systematic review.

Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA. Methods. An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically. Results. We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion. Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.

Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke.

BACKGROUND AND PURPOSE: An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. METHODS: Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. RESULTS: Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. CONCLUSIONS: In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Anesthesia for endovascular treatment of acute ischemic stroke.

The initial treatment of patients with acute ischemic stroke (AIS) focuses on rapid recanalization, which often includes the use of endovascular therapies. Endovascular treatment depends upon micronavigation of catheters and devices into the cerebral vasculature, which is easier and safer with a motionless patient. Unfortunately, many stroke patients are unable to communicate and sufficiently cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal intubation provides an attractive means of keeping the patient comfortable and motionless during a procedure that could otherwise be lengthy and uncomfortable. However, several recent retrospective studies have shown an association between GA and poorer outcomes in comparison with conscious sedation for endovascular treatment of AIS, though prospective studies are lacking. The underlying reasons why GA might produce a worse outcome are unknown but may include hemodynamic instability and hypotension, delays in treatment, prolonged intubation with or without neuromuscular blockade, or even neurotoxicity of the anesthetic agent itself. Currently, the choice between GA and conscious sedation should be tailored to the individual patient, on the basis of neurologic deficits, airway and hemodynamic status, and treatment plan. The use of institutional treatment protocols may best support efficient and effective care for AIS patients undergoing endovascular therapy. Important components of such protocols would include parameters to choose anesthetic modality, timeliness of induction, blood pressure goals, minimization of neuromuscular blockade, and planned extubation at the end of the procedure.

Cerebral venous and sinus thrombosis associated with subcutaneous immunoglobulin injection and oral contraceptive use.

Although patients of cerebral sinus thrombosis after intravenous immunoglobulin (IVIG) has been previously reported; reports of cerebral venous thrombosis secondary to subcutaneous injection of immunoglobulin (SIG) in conjunction with oral contraceptives are nonexistent in the current literature. We describe here a patient of cerebral venous and sinus thrombosis occurring after the combination of SIG and oral contraceptive use. Furthermore, we shall explore proper clinical precautions for someone who receives IG therapy, especially in conjunction with the use of oral contraceptives.

ABCD2 Score and Large-Artery Atherosclerosis.

BACKGROUND AND PURPOSE: Extracranial stenosis (ECS) or intracranial stenosis (ICS) are independent risk factors for stroke after transient ischemic attack (TIA). We examined the association of the age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score, a validated risk prediction model for stroke after TIA, and the presence of ICS or ECS. METHODS: Vascular imaging and ABCD2 scores were obtained in a retrospective cohort of 77 consecutive patients diagnosed with TIA in a single center emergency department. The association between vascular stenosis and ABCD2 scores and how each related to clinical outcome was examined. RESULTS: In all, 30 (39.2%) TIA patients had 37 stenotic lesions; 15 (40.5%) stenotic lesions were ICS and 22 (59.5%) stenotic lesions were ECS. A total of 7 patients (9.5%) had both ECS and ICS lesions. Patients with ABCD2 > 3 were more likely to have ICS (odds ratio [OR] = 6.25, confidence interval [CI] 1.39-32.44, P = .009) and ECS (OR = 5.25, CI = 1.56-17.66, P = .005). Of the 37 stenotic lesions, 21 (56.7%) were symptomatic; 4 (19.2%) of these had an ABCD2 ≤ 3. At 7 days, there were 4 ischemic strokes, 3 had previously demonstrated symptomatic stenotic lesions, and all had ABCD2 scores > 3. CONCLUSIONS: Compared to patients in the low-risk ABCD2 scores, the patients with medium- to high-risk ABCD2 scores are more likely to have symptomatic and asymptomatic vascular stenotic lesions. However, 1 in 5 patients with low-risk ABCD2 score has symptomatic stenotic lesions, indicating ABCD2 score does not identify all patients with symptomatic stenotic lesions.

Neurohospitalists Improve Door-to-Needle Times for Patients With Ischemic Stroke Receiving Intravenous tPA.

PURPOSE: It is unknown whether neurohospitalist evaluation improves door-to-needle times (DNT) in patients with acute ischemic stroke.The purpose of this study is to determine the impact of neurohospitalist evaluation on DNT for patients with ischemic stroke receiving intravenous tissue plasminogen activator (tPA) presenting within 4.5 hours of symptom onset. METHODS: We retrospectively identified consecutive patients with ischemic stroke who received tPA between 0 and 4.5 hours. We determined and compared DNT for nonneurohospitalists versus neurohospitalists for a 26-month period from 2009 to 2011. Our main outcome measure was percentage of patients receiving tPA within 60 minutes. RESULTS: Overall, out of the 107 consecutive ischemic stroke patients (mean age 67 years) who received intravenous tPA within 4.5 hours, 60 patients were evaluated by nonneurohospitalists (community and locums neurologists) and 47 patients were evaluated by neurohospitalists. Mean ± standard deviation (SD) DNT with patients treated by nonneurohospitalists (93 ± 24 minutes) were significantly longer than the DNT treated by neurohospitalists (68 ± 18 minutes). Twenty-four patients (51%) treated by neurohospitalists had DNT less than or equal to 60 minutes, while 9 patients (15%) treated by nonneurohospitalists had DNT less than or equal to 60 minutes. Multivariate analysis showed that neurohospitalist evaluation (odds ratio [OR] 5.4, confidence interval [CI] 2.2-13.6, P = .022) was the only independent factor associated with patients receiving tPA within 60 minutes. CONCLUSION: Neurohospitialist evaluation is associated with faster DNT in patients with ischemic stroke. Neurohospitalist evaluation could be a part of a multidimensional initiative to improve the timeliness of tPA administration.

Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia.

The present study sought to determine the neuroprotective effect of anthocyanin cyanidin-3-O-glucoside (CG), isolated and purified from tart cherries, against permanent middle cerebral artery occlusion (pMCAO) in mice and its potential mechanisms of neuroprotection. C57BL/6 mice subjected to pMCAO were treated with CG orally. Twenty-four hours after pMCAO, neurological scoring was used to evaluate functional outcome. The brains were then excised for measuring infarct volume and brain superoxide levels were determined. In a separate set of experiments, the influence of CG on cytochrome c (cyt c) and apoptosis-inducing factor (AIF) release from mitochondria under oxidative stress were assessed in isolated cortical neurons from adult mouse brains. Infarction volume was attenuated by 27% in mice pre-treated with 2mg/kg of CG compared to vehicle-treated mice. Delayed treatment with 2mg/kg of CG also showed 25% reduction in infarct size. Neurological functional outcome was significantly improved in mice pre- or post-treated with CG. Compared to vehicle treated mice CG treated mice had lower levels of brain superoxide. CG also blocked the release of AIF from mitochondria under oxidative stress, but did not inhibit the release of cyt c. Our data show that CG is neuroprotective against pMCAO in mice, and this beneficial effect may be mediated by attenuation of brain superoxide levels after ischemia. CG may also exert its neuroprotective effect by blocking AIF release in mitochondria.

Clinical significance of serum zinc levels in cerebral ischemia.

Background. Zinc mediates several vital physiological, enzymatic and cellular functions. The association between serum zinc and stroke outcome has not been previously evaluated. Methods. This single center retrospective study was conducted on consecutive stroke (n = 158) and TIA (n = 74) patients. We sought to determine whether serum zinc concentrations in patients with acute ischemic strokes were associated with stroke severity and poor functional status at discharge, respectively. Results. Overall, out of the 224 patients analyzed (mean age 67 years), 35.7% patients had low zinc levels (65 mcg/dL). Patients with stroke (n = 152) were more likely to have low zinc levels (OR = 2.62, CI 1.92-3.57, P < .003) compared to patients with TIA (n = 72). For patients with stroke (n = 152), multivariate analysis showed that low serum zinc levels (OR 2.82, CI 1.35-5.91, P = .035) and strokes with admission severe strokes (NIHSS > 8) (OR 2.68, CI 1.1-6.5, P = .03) were independently associated with poor functional status (MRS > 3) at discharge from the hospital. Conclusion. Low serum zinc concentrations are associated with more severe strokes on admission and poor functional status at discharge.

Predictors of occult paroxysmal atrial fibrillation in cryptogenic strokes detected by long-term noninvasive cardiac monitoring.

Background and Purpose. Paroxysmal Atrial fibrillation/Flutter (PAF) detection rates in cryptogenic strokes have been variable. We sought to determine the percentage of patients with cryptogenic stroke who had PAF on prolonged non-invasive cardiac monitoring. Methods and Results. Sixty-two consecutive patients with stroke and TIA in a single center with a mean age of 61 (+/- 14) years were analyzed. PAF was detected in 15 (24%) patients. Only one patient reported symptoms of shortness of breath during the episode of PAF while on monitoring, and 71 (97%) of these 73 episodes were asymptomatic. A regression analysis revealed that the presence of PVCs (ventricular premature beats) lasting more than 2 minutes (OR 6.3, 95% CI, 1.11-18.92; P = .042) and strokes (high signal on Diffusion Weighted Imaging) (OR 4.3, 95% CI, 5-36.3; P = .041) predicted PAF. Patients with multiple DWI signals were more likely than solitary signals to have PAF (OR 11.1, 95% CI, 2.5-48.5, P < .01). Conclusion. Occult PAF is common in cryptogenic strokes, and is often asymptomatic. Our data suggests that up to one in five patients with suspected cryptogenic strokes and TIAs have PAF, especially if they have PVCs and multiple high DWI signals on MRI.

The ABCD and ABCD2 Scores and the Risk of Stroke following a TIA: A Narrative Review.

The California, ABCD, and ABCD2 risk scores (ABCD system) were developed to help stratify short-term stroke risk in patients with TIA (transient ischemic attack). Beyond this scope, the ABCD system has been extensively used to study other prognostic information such as DWI (diffusion-weighted imaging) abnormalities, large artery stenosis, atrial fibrillation and its diagnostic accuracy in TIA patients, which are independent predictors of subsequent stroke in TIA patients. Our comprehensive paper suggested that all scores have and equivalent prognostic value in predicting short-term risk of stroke; however, the ABCD2 score is being predominantly used at most centers. The majority of studies have shown that more than half of the strokes in the first 90 days, occur in the first 7 days. The majority of patients studied were predominantly classified to have a higher ABCD/ABCD2 > 3 scores and were particularly at a higher short-term risk of stroke or TIA and other vascular events. However, patients with low risk ABCD2 score < 4 may have high-risk prognostic indicators, such as diffusion weighted imaging (DWI) abnormalities, large artery atherosclerosis (LAA), and atrial fibrillation (AF). The prognostic value of these scores improved if used in conjunction with clinical information, vascular imaging data, and brain imaging data. Before more data become available, the diagnostic value of these scores, its applicability in triaging patients, and its use in evaluating long-term prognosis are rather secondary; thus, indicating that the primary significance of these scores is for short-term prognostic purposes.

Elevated levels of pre-procedural high-sensitivity C-reactive protein is associated with midterm restenosis after extra- and intracranial stenting.

BACKGROUND AND PURPOSE: High-sensitivity C-reactive protein (hsCRP) is an inflammatory marker associated with subsequent coronary events and neointimal hyperplasia after coronary artery stent placement. We sought to determine if elevated levels of hsCRP are associated with restenosis after placement of extra- and intracranial stents. METHODS: We retrospectively reviewed 73 consecutive patients at Michigan State University from July 2006 until June 2007 who underwent treatment with carotid artery stent placement or intracranial stent placement. Data were collected in regards to demographics, pre-procedural hsCRP, and LDL levels, and angiographic variables characterizing the lesion before and after treatment. A binary logistic regression model was constructed to determine independent predictors of restenosis. RESULTS: A total of 73 patients with a mean age of 69 +/- 11 years were studied. A total of 57 patients were treated with extracranial carotid stenting, 22 (38%) of whom were symptomatic, while 16 patients underwent intracranial stenting (all were symptomatic). There were 9 patients (4 intracranial stents [25%] and 5 carotid stents [8.8%]) who developed a restenosis of >50%. In binary logistic regression modeling, the following variables were found to be independently predictive of developing restenosis: smaller vessel diameter (OR .49, 95% CI .23-.98, P-value .046) and elevated hsCRP (OR 2.2, 95% CI 1.29-6.66, P-value .018). CONCLUSIONS: Elevated levels of pre-procedural hsCRP may be predictive of the development of neointimal hyperplasia in patients treated with extra- or intracranial stenting procedures. Future prospective multicenter studies will be required to confirm these findings.

Neurotoxic and cardiotoxic effects of cocaine and ethanol.

INTRODUCTION: Concurrent abuse of alcohol and cocaine results in the formation of cocaethylene, a powerful cocaine metabolite. Cocaethylene potentiates the direct cardiotoxic and indirect neurotoxic effects of cocaine or alcohol alone. CASE REPORT: A 44-year-old female with history of cocaine and alcohol abuse presented with massive stroke in the emergency department. CT scan revealed extensive left internal carotid artery dissection extending into the left middle and anterior cerebral arteries resulting in a massive left hemispheric infarct, requiring urgent decompressive craniectomy. The patient had a stormy hospital course with multiple episodes of torsades de pointes in the first 4 days requiring aggressive management. She survived all events and was discharged to a nursing home with residual right hemiplegia and aphasia. CONCLUSION: The combination of ethanol and cocaine has been associated with a significant increase in the incidence of neurological and cardiac emergencies including cerebral infarction, intracranial hemorrhage, myocardial infarction, cardiomyopathy, and cardiac arrhythmias. The alteration of cocaine pharmacokinetics and the formation of cocaethylene have been implicated, at least partially, in the increased toxicity of this drug combination.

Diffusion-weighted imaging: not all that glitters is gold.

Diffusion-weighted imaging (DWI) is a sophisticated magnetic resonance imaging (MRI) technique with rapid acquisition time and high sensitivity for depicting acute cerebral ischemia. It is currently part of the routine workup in most medical centers when ischemic stroke is in the differential diagnosis. DWI helps establish a diagnosis of acute ischemic infarct even in cases where the clinical presentation is not typical for ischemic stroke. However, contrary to popular belief, not every hyperintensity on DWI is an ischemic stroke. Consequently, DWI with high intensity signals, commonly called "positive" DWI, is sometimes misinterpreted and leads to incorrect medical management. In this report, we briefly discuss some of the essential, technical aspects of DWI and report various clinical scenarios, which may lead to "positive" DWI findings but are not ischemic strokes. Although the sensitivity of DWI for ischemic stroke is very high, the specificity is not as high, and a "positive" DWI does not exclude other diagnoses that should be considered based on each patient's clinical history and examination, and the appearance of other sequences of MRI scans.