Utility of tPA Administration in Acute Treatment of Internal Carotid Artery Occlusions.

Background: Intravenous tissue plasminogen activator (IV-tPA) remains part of the guidelines for acute ischemic stroke treatment, yet internal carotid artery occlusions (ICAO) are known to be poorly responsive to IV-tPA. It is unknown whether bridging thrombolysis (BT) is beneficial in such cases. Purpose: We sought to evaluate whether the use of IV-tPA improved overall clinical outcomes in patients undergoing endovascular thrombectomy (EVT) for ICA occlusions. Methods: Data from 1367 consecutive stroke cases treated with EVT from 2012-2019 were prospectively collected from a single center. Univariate and multivariate logistic regression were used to assess the relationship between IV-tPA administration and clinical outcome. Results: 153 patients were found to have carotid terminus and tandem ICAO who received EVT and presented within 4.5h of last seen well. 50% (n = 82) received IV tPA. There were no differences between the groups with respect to age, NIHSS, time to EVT and ASPECTS score. 53% had tandem ICA-MCA occlusions. Rate of recanalization (≥ TICI 2B) and sICH did not significantly differ between the two groups. Regression analysis demonstrated no effect of IV-tPA on modified Rankin Score (mRS) at 90 days and overall mortality. Factors significantly associated with reduced mortality included lower age, lower NIHSS, and better rate of recanalization. Conclusions: There was no significant difference in clinical outcomes in those receiving BT vs. direct EVT for ICAO. For centers with optimal door-to-puncture times, bypassing IV-tPA may expedite recanalization times and potentially yield more favorable outcomes. Patients with higher NIHSS and tandem lesions may have better outcomes with BT.

Expedited Management of Low-Risk Transient Ischemic Attack Patients: The "Fast-Track" TIA Protocol.

OBJECTIVES: Transient ischemic attack (TIA) serves a precursor for an acute ischemic stroke (AIS); however, not all TIA patients harbor the same risk for subsequent AIS. We aimed to investigate expediting outpatient management of low-risk TIA patients (ABCD: Giles and Rothwell, 2007 score ≤ 3) via our "Fast-Track" TIA Protocol (FTTP). MATERIALS AND METHODS: A retrospective analysis was performed on patients who presented to our academic network 04/2020 - 2/2021. Patients who presented with ABCD: Giles and Rothwell, 2007 scores ≤ 3 without large vessel occlusion or flow limiting stenosis were eligible for the FTTP. These patients were discharged on dual antiplatelet therapy and statin and received prescriptions for transthoracic echo, holter monitor, LDL, and A1c along with a scheduled follow-up appointment 30 days from presentation. RESULTS: 182 consecutive patients were evaluated during this period, 21 (11%) were excluded from analysis due to NIHSS > 0 and/or infarct present on MRI. 35 (22%) patients qualified for FTTP and were directly discharged from the ED. Median ABCD2 score was 2 for the discharge group and 4 for the admitted group. There was a significant difference with respect to age and hypertension. Additionally, the FTTP patient population were more likely to be smokers than the admitted patient population. 3 FTTP patients re-presented to the ED, but none of them suffered a symptomatic stroke. CONCLUSIONS: A FTTP demonstrated feasibility and safety with low rates of re-presentation and ischemic stroke. Further research is warranted to determine an optimal patient population that can be safely managed in an outpatient setting.

Transcirculation Embolization to New Territory During Mechanical Thrombectomy for Acute Ischemic Stroke.

Embolization in new territories (ENT) is a known complication of mechanical thrombectomy with incidence dependent upon a variety of procedural factors. We present 2 cases of anterior circulation to posterior circulation ENT. These cases were managed with manual aspiration thrombectomy with excellent radiographic and clinical outcome. We present the available literature involving ENT along with our experience in management.

Causes, Predictors, and Timing of Early Neurological Deterioration and Symptomatic Intracranial Hemorrhage After Administration of IV tPA.

BACKGROUND: Acute ischemic stroke (AIS) is a major contributor toward healthcare-associated costs and services. Symptomatic intracranial hemorrhage (sICH) and early neurologic decline (END), defined as a National Health Institute Stroke Scale score decline of ≥ 4 within 24 h (with or without sICH), remain major concerns when administering intravenous tissue plasminogen activator (IV tPA) despite improved functional neurologic outcomes with its use. Given these risks, current guidelines recommend comprehensive stroke care (most often in an intensive care unit setting) for 24 h posttreatment. However, a number of patients may remain stable after IV tPA and thus not require such intensive resources. We sought to determine causes of END, along with timing and predictors of both sICH and END, to identify patients at lower risk of neurological deterioration and those suitable for earlier transition to a lower level of care. METHODS: This present study analyzed patients with AIS that presented within 4.5 h of being last seen well and received IV tPA. Baseline demographic, clinical, and radiographic findings were collected. Outcomes included END from any cause, parenchymal hemorrhage (PH1 or PH2), sICH, and mortality at 90 days. RESULTS: A total of 1238 patients with AIS without acute treatment of large vessel occlusion received IV tPA. 9.4% (116) had presence of any degree of ICH on noncontrast computed tomography head and 7.4% (91) experienced associated END. 2.7% (33) of patients experienced sICH, while 6.7% (83) experienced asymptomatic ICH. Of the patients with END, 63.7% did not have ICH. Predictive factors at presentation for END included an older age (72.6 ± 16.1 vs. 69.1 ± 14.8, p = 0.03), history of tobacco use (odds ratio [OR] 2.1 [1.1-4.3], p = 0.04), and hyperlipidemia (OR 1.7 [1.1-2.8], p = 0.02), along with the presence of an untreated large vessel occlusion (OR 2.1 [1.4-3.1], p = 0.02). Most END occurred within a mean time of 242 ± 251 min (4 ± 4 h). Because of the small proportion of patients suffering from sICH (33), predictors could not be determined; however, for patients with any ICH, predictive factors included an older age (74.6 ± 12.4 vs. 68.8 ± 15.1, p = 0.001), higher baseline National Health Institute Stroke Scale score (14.6 ± 7.3 vs. 10.8 ± 7.9, p = 0.002), and higher baseline glucose levels (155.1 ± 87.5 vs. 140.4 ± 70.5, p = 0.04). CONCLUSIONS: In this study, only a small proportion suffered from either sICH and/or END, typically within 12 h of tPA administration. These findings may support earlier deescalation of higher acuity monitoring in clinically stable post-IV tPA patients without large vessel occlusion.

Intravenous tPA Delays Door-To-Puncture Time in Acute Ischemic Stroke with Large Vessel Occlusion.

OBJECTIVE: Although intravenous thrombolysis (IVT) is recommended among acute ischemic stroke (AIS) patients secondary to large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT), time delays with bridging therapy (IVT prior to MT) and its potential benefit remains unclear. We compared the time delays and clinical outcomes among AIS SECONDARY TO LVO patients treated with bridging therapy or direct MT (dMT) at a comprehensive stroke center (CSC). METHODS: We performed a retrospective analysis of prospectively collected data of AIS secondary to LVO patients admitted between 2012 and 2017 at a large volume CSC. AIS secondary to LVO patients arriving directly from field to CSC within 4.5 h were included. Demographic characteristics, clinical and radiological data, treatment and procedural information were extracted and analyzed. RESULTS: Among 777 AIS secondary to LVO patients treated with MT, 237 patients (156 dMT, 81 bridging therapy) were included. Mean age was 70.3 year-old, median NIHSS score was 18, and door-to-needle time was 40 min (IQR 31-56 min). The median door-to-puncture (DTP) time was 22 min longer in bridging therapy group in comparison to dMT group, 74 vs 52 min (p<0.001). Additionally, no difference was observed between the groups for successful recanalization or functional independence. CONCLUSION: At a large volume CSC, bridging therapy (vs. dMT) was observed to have a longer DTP time without any difference in successful recanalization or clinical outcomes.

Capitated pricing model for stroke thrombectomies: a single center experience across three companies.

BACKGROUND: With a continued rise in healthcare expenditures, there is a demonstrable focus on curbing expenses. Mechanical thrombectomy (MT) is the standard of treatment for large vessel occlusions (LVOs); however, considerable costs are associated with devices utilized in each procedure. We report our institution's experience with capitation pricing models negotiated with three different companies. METHODS: We retrospectively reviewed a prospectively maintained database from February 2018 to August 2019 identifying cases performed under capitation models. We calculated the cost of equipment for each thrombectomy using the cost for individual devices utilized (virtual) and compared this sum to the total derived from cost-negotiated bundled equipment packages. This was compared with real-world cases that did not meet capitation criteria during this study period. RESULTS: 107 cases met the criteria for capitation; 39 cases used company A's models (28 with stentrievers), 44 cases used company B's models (3 with stentrievers), and 24 cases used company C's models (14 with stentrievers). Overall, there was a net savings of $202 370.50 utilizing the capitated model ($689 435 vs $891 805.50), amounting to $1891.31 savings per case. Mean capitation was lower ($6972±2774) compared with virtual ($8794±4614) and real-world non-capitation costs ($7176±3672). CONCLUSION: The negotiated capitated pricing model yielded total cost savings associated with equipment from each company. Overall mean capitation costs were lower than virtual and real-world cases. This may serve as a model for other centers in controlling costs for patients undergoing MT for LVO.

Ballast and NeuronMax in stroke thrombectomy.

BACKGROUND: Comparative evaluation of long sheath performance in stroke thrombectomy has not been performed. OBJECTIVE: To review an initial experience with the new Ballast 6F long sheath compared with the NeuronMax, to evaluate comparative benchmarks in trackability, navigability, and procedural outcomes. METHODS: A prospectively maintained thrombectomy database was evaluated over a 6-month period to compare procedural and angiographic results between a cohort of patients treated with the historical institutional standard long sheath (NeuronMax) and another with the new Ballast long sheath via a transfemoral approach. RESULTS: Of 156 stroke thrombectomy cases, 69 were performed using NeuronMax and 40 using Ballast via a transfemoral approach; the remainder of cases employed alternative long sheaths or were performed via initial radial access. There was no significant difference in patient age, medical history, baseline National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, arch type, tissue plasminogen activator use, and clot location between the two groups. Single-pass case frequency (41% for NeuronMax vs 44% for Ballast, p=0.84), and final successful revascularization (TICI 2b or greater) were similar between the two cohorts (91% vs 98%, p=0.42). Good 90-day outcome (modified Rankin Scale score 0-2) was also similar (33% for NeuronMax, 43% for Ballast, p=0.41). Excluding tandem occlusions, mean procedural time was 31 min for NeuronMax and 25 min for Ballast (p=0.09). Puncture to long sheath access and angiography in the base target vessel was faster for Ballast than NeuronMax (6.5 min vs 9.2 min, p=0.04). CONCLUSION: Among a cohort of practitioners with historical, preferential experience with NeuronMax for stroke thrombectomy, faster procedural times were achieved with Ballast with similar final angiographic results.

Cost of hospitalization for aneurysmal subarachnoid hemorrhage in the United States.

OBJECTIVE: Recent large-scale studies describing hospitalization cost trends secondary to aneurysmal subarachnoid hemorrhage (aSAH) in the United States are lacking. We sought to discover the impact of aSAH-related factors upon its hospitalization cost. PATIENTS AND METHODS: Patients with a primary diagnosis of aSAH were selected utilizing the National Inpatient Sample. Regression analyses were used to evaluate the impact of aSAH-related factors on hospitalization costs. RESULTS: From 2002-2014, 22,831 cases of aSAH were identified. The inflation-adjusted mean cost of hospitalization was $82,514 (standard deviation ± $54,983). The proportion of males was lower (31%), but a higher cost of $3385 (± $685; p < .001) remained compared to females. Median length of hospitalization was 16 days (interquartile range 11-23) and each day increase in hospitalization was associated with a cost increase of $3228 (± $19; p < .001). There was no difference in cost between patients undergoing aneurysmal coiling or clipping. When compared to patients < 40 years old, the increase in cost for patients 40-59 years old was $3829 (± $914; p < .001), and $4573 (± $1033; p < .001) for patients 60-79 years old; however, for patients ≥ 80 years old, there was a decrease in cost of $8124 (± $1722; p < .001). Several central nervous system complications were also associated with increased cost. CONCLUSION: aSAH is a significant financial burden on the United States healthcare system. We were able to identify many important factors associated with higher costs, and these results may help us understand resource utilization and develop future cost-reduction strategies.

Education Research: Electronic patient portal enrollment and no-show rates within a neurology resident clinic.

OBJECTIVE: To identify factors that affect appointment adherence and investigate the association of electronic patient portal (ePP) enrollment and patient adherence rates to appointments in the Neurology Resident Clinic (NRC). METHODS: Patients scheduled for an appointment during the months of October 2015, February 2016, and June 2016 in the NRC were included. ePP enrollment, date of clinic appointment, method of referral to the clinic, and key demographic criteria were collected. χ2 tests were performed to assess the association of appointment status (i.e., no-show, showed, and canceled) with demographic, comorbidity, and visit information. RESULTS: Patients with ePP enrollment had significantly lower rates of no-show (19% vs 27%) and higher rates of showed (59% vs 48%) compared to patients without ePP enrollment. Younger patients (18-49) had the highest rates of no-show (28%), while older patients (65+) had the lowest rates of no-show (17%). Caucasian patients had significantly lower rates of no-show compared to non-Caucasian patients (14% vs 24%). Non-English-speaking patients had high rates of no-show (34%). Patients with a physician referral had significantly lower rates of no-show (20% vs 28%) and higher rates of showed (61% vs 44%) compared to patients with a self-referral. CONCLUSIONS: Our study indicates that ePP enrollment, age, race, and physician referral might be associated with reduced no-show rates in the NRC.

Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood.

The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT-qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 log-linear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resource-limited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats.

The Evolution and Application of Cardiac Monitoring for Occult Atrial Fibrillation in Cryptogenic Stroke and TIA.

OPINION STATEMENT: The evaluation of the stroke and transient ischemic attack (TIA) patient has been historically predominated by the initial evaluation in the hospital setting. As the etiology of stroke has eluded us in approximately one third of all acute events, the medical community has been eager to seek the answer to this mystery. In recent years, we have seen an explosion of innovations and trends allowing for a more detailed post stroke assessment strategy aimed at the identification of occult atrial fibrillation as the etiologic cause for the cryptogenic event. This has been achieved through the evolution and aggressive application and study of prolonged and advanced cardiac monitoring. This review is aimed to clarify and elucidate the standard and novel cardiac monitoring methods that have become available for use by the medical community and expected in the higher level care of cryptogenic stroke and TIA patients. These cardiac monitoring methods and devices are as heterogeneous as our patient population and have their own advantages and disadvantages. Many factors may be taken into consideration in choosing the appropriate cardiac monitoring method and are highlighted for consideration in this review. With a judicious approach to investigating the cryptogenic stroke population, and applying a wealth of novel treatment options, we may move forward into a new era of stroke prevention.

Predictors of Outcomes in Traumatic Brain Injury.

INTRODUCTION: The purpose of this study was to retrospectively evaluate patients treated for traumatic brain injuries (TBI) to determine how multiple organ trauma (MOT) and lung injuries sustained at the time of initial injury affect outcome. METHODS: A single institution retrospective review of all patients diagnosed with TBI at a level I trauma center from 2000 to 2014 was conducted. Clinical outcome was based on Glasgow Outcome Scale at hospital discharge. Lung injury was defined as the presence of pulmonary contusions, pneumothorax, hemothorax, rib fractures, or diaphragmatic rupture proven by x-ray or computed tomography scan. MOT was defined as trauma to one body region with an Abbreviated Injury Scale (AIS) score ≥3 plus trauma to 2 additional body regions with AIS scores ≥1. Regression analysis was conducted with SPSS 21. RESULTS: There were 409 patients reviewed. The majority of patients were male (73%), average age was 46 years (range, 16-94 years), average Glasgow Coma Scale (GCS) score was 7, and 71% had a severe TBI (GCS ≤8). Thirty percent of patients had poor outcome (Glasgow Outcome Scale = 1-2) Regression analysis indicated age (odds ratio [OR] 1.03, P < 0.001), initial GCS (OR 0.88, P < 0.001), Injury Severity Score (OR 1.03, P = 0.021), and head AIS ≥5 (OR 0.55, P = 0.019) were significant independent predictors of poor outcome. Sex, MOT, lung injury, and lung injury severity were not significant predictors of outcome. CONCLUSIONS: Age, GCS, Injury Severity Score, and critical head injuries (AIS ≥5) were significant tools in predicting outcome in this patient cohort. MOT and traumatic lung injury may cause significant damage to a patient suffering from a severe TBI, but these injuries do not predict mortality in this patient population.

Adverse childhood experiences are associated with migraine and vascular biomarkers.

OBJECTIVES: Migraine is a risk factor for stroke in young women. Biomarker studies implicate endothelial activation as a possible mechanism. Emerging relationships of childhood adversity with migraine, and with inflammation, a component of endothelial activation, suggest that it may play a role in the migraine-stroke association. Our objective is to evaluate the relationship between adverse childhood experiences (ACEs), migraine, and vascular biomarker levels in premenopausal women. METHODS: Vascular and metabolic biomarkers from women 18-50 years, including 125 with migraine (interictal) and 50 without migraine, were evaluated. An ACE questionnaire was later collected by mail (response rate 80.6%, 100 migraineurs, 41 controls). RESULTS: Migraineurs and controls were demographically similar. Migraineurs reported adversity more commonly than controls (71% vs 46%, odds ratio [OR] = 1.53, 95% confidence interval 1.07-2.17). Average ACE scores were elevated in migraineurs as compared with controls (2.4 vs 0.76, P < .001). ACE scores correlated with headache frequency (0.37, P = .001) and younger age of headache onset (-0.22, P = .04). It also correlated with body mass index (r = 0.43, P = .0001), von Willebrand factor activity (r = 0.21, P = .009), tissue plasminogen activator antigen (r = 0.28, P = .004), prothrombin activation fragment (r = 0.36, P = .001), high-sensitivity C-reactive protein (r = 0.98, P = .0001), transforming growth factor-beta1 (r = 0.28, P = .003), tissue necrosis factor-alpha (r = 0.20, P = .03), interleukin-6 (r = 0.22, P = .03), adiponectin (r = -0.29, P = .003), and nitrate/nitrite concentration (r = -314, P = .001). Logistic regression analyses (adjusted for vascular risk factors and migraine) demonstrated an association of childhood adversity with inflammatory factors (high-sensitivity C-reactive protein, interleukin-6, and tissue necrosis factor-alpha). CONCLUSIONS: In young women, adverse childhood events are associated with migraine, particularly chronic and transformed migraine, and with vascular biomarkers, especially inflammatory biomarkers. These findings implicate early life stress as a link between migraine and endothelial activation.