Thrombolytic therapy for wake-up stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake-up stroke [WUS]), which renders patients ineligible for IV tPA administered via time-based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta-analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging-based treatment algorithms. METHODS: We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single-arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)- or computed tomography (CT)-based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects. RESULTS: We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI-based (five studies) or CT-based (10 studies) imaging selection, and one study used a combination of modalities. Sixty-one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%-70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01-1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%-4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85-5.61, seven studies). CONCLUSIONS: This systematic review and meta-analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.

A Blueprint for the Conduct of Large, Multisite Trials in Telemedicine.

Recent literature supports the efficacy and efficiency of telemedicine in improving various health outcomes despite the wide variability in results. Understanding site-specific issues in the implementation of telemedicine trials for broader replication and generalizability of results is needed. Lessons can be learned from existing trials, and a blueprint can guide researchers to conduct these challenging studies using telemedicine more efficiently and effectively. This viewpoint presents relevant challenges and solutions for conducting multisite telemedicine trials using 7 ongoing and completed studies funded by the Patient-Centered Outcomes Research Institute portfolio of large multisite trials to highlight the challenges in implementing telemedicine trials. Critical issues of ensuring leadership and buy-in, appropriate funding, and diverse and representative trials are identified and described, as well as challenges related to clinical, informatics, regulatory, legal, quality, and billing. The lessons learned from these studies were used to create a blueprint of key aspects to consider for the design and implementation of multisite telemedicine trials.

A Pilot Randomized Controlled Trial of the Feasibility of a Multicomponent Delirium Prevention Intervention Versus Usual Care in Acute Stroke.

BACKGROUND: Delirium after acute stroke is a serious complication. Numerous studies support a benefit of multicomponent interventions in minimizing delirium-related complications in at-risk patients, but this has not been reported in acute stroke patients. The purpose of this study was to explore the feasibility of conducting a randomized (delirium care) versus usual standardized stroke care (usual care) in reducing delirium in acute stroke. OBJECTIVE: This pilot study assessed the feasibility of (1) enrollment within the 48-hour window when delirium risk is greatest, (2) measuring cognitive function using the Montreal Cognitive Assessment, (3) delivering interventions 7 days per week, and (4) determining delirium incidence in stroke-related cognitive dysfunction. METHODS: A 2-group randomized controlled trial was conducted. Patients admitted with ischemic and hemorrhagic strokes and 50 years or older, English speaking, and without delirium on admit were recruited, consented, and randomized to usual care or delirium care groups. RESULTS: Data from 125 subjects (delirium care, n = 59; usual care, n = 66) were analyzed. All Montreal Cognitive Assessment subscales were completed by 86% of subjects (delirium care, mean [SD], 18.14 [6.03]; usual care, mean [SD], 17.61 [6.29]). Subjects in the delirium care group received a mean of 6.10 therapeutic activities (range, 2-23) and daily medication review by a clinical pharmacist using anticholinergic drug calculations. Delirium incidence was 8% (10/125), 3 in the delirium care group and 7 in the usual care group. CONCLUSION: Findings support the feasibility of delivering a multicomponent delirium prevention intervention in acute stroke and warrants testing intervention effects on delirium outcomes and anticholinergic medication administration.

A stroke/vascular neurology service increases the volume of urgent carotid endarterectomies performed in a tertiary referral center.

BACKGROUND: Increasing evidence supports that urgent carotid endarterectomy (CEA), defined as CEA during the index hospitalization, may be undertaken in select patients with acute carotid-related neurologic symptoms to prevent recurrent ischemic events. We aimed to determine the effect of a stroke/vascular neurology service on the volume of urgent CEAs performed and assess perioperative outcomes. METHODS: A retrospective review from a single tertiary referral center between June 2005 through December 2011 revealed 393 patients who underwent CEA. We identified the number of urgent CEAs before (June 2005-August 2008) and after (September 2008-December 2011) a stroke/vascular neurology service was implemented, as well as asymptomatic CEAs and symptomatic but electively performed CEAs. Demographic data as well as 30-day adverse outcomes (transient ischemic attack [TIA], stroke, myocardial infarction, and mortality) were analyzed for each group. In patients undergoing urgent CEA, TIA and stroke severity were assessed by a stroke neurologist using the ABCD2 TIA score and National Institutes of Health Stroke Scale (NIHSS), respectively. The χ2 test was used to compare differences between the urgent CEA volume before and after a stroke/vascular neurology service. Fisher's exact test was used to analyze perioperative outcomes. RESULTS: Demographics and comorbidities were similar between the 2 groups. The proportion of urgent CEAs performed increased significantly after initiation of a vascular neurology service (4.1% [7 of 172] vs. 22.2% [49 of 221], P<0.0001). Per annum, urgent CEAs increased from 5.3% (4/75) in 2005 to 39.6% (25/63) in 2011. A vascular neurology service did not increase the number of nonurgent referrals. Urgent CEA indications were ocular ischemic events 4% (2/49), cerebral ischemic/infarction events 35% (17/49), crescendo TIAs 6% (3/49), acute stroke 45% (22/49), and stroke-in-evolution 10% (5/49). Mean NIHSS was 3.5 (range 0-24); mean TIA score was 5 (range 1-8). Although there were no statistical differences in 30-day outcomes, there was a trend toward a higher combined complication rate (stroke, death, myocardial infarction) in the urgent compared with the symptomatic but electively performed CEA group (7.1 % [3/49] vs. 2% [1/49]; P=.36). However, patients undergoing urgent CEA with an NIHSS<10 had no perioperative complications. CONCLUSIONS: Collaboration with a vascular neurology team increased the volume of urgent CEAs over a 3-year period. In patients with mild-to-moderate strokes (NIHSS<10), urgent CEA perioperative outcomes approximate those for electively performed CEAs, suggesting improved care through a multidisciplinary approach.

Diagnostic accuracy of telestroke consultation: a Louisiana based tele-network experience.

Background and purpose: Telestroke has grown significantly since its implementation. Despite growing utilization, there is a paucity of data regarding the diagnostic accuracy of telestroke to distinguish between stroke and its mimics. We aimed to evaluate diagnostic accuracy of telestroke consultations and explore the characteristics of misdiagnosed patients with a focus on stroke mimics. Methods: We conducted a retrospective study of all the consultations in our Ochsner Health's TeleStroke program seen between April 2015 and April 2016. Consultations were classified into one of three diagnostic categories: stroke/transient ischemic attack, mimic, and uncertain. Initial telestroke diagnosis was compared with the final diagnosis post review of all emergency department and hospital data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for diagnosis of stroke/TIA versus mimic were calculated. Area under receiver-operating characteristic curve (AUC) analysis to predict true stroke was performed. Bivariate analysis based on the diagnostic categories examined association with sex, age, NIHSS, stroke risk factors, tPA given, bleeding after tPA, symptom onset to last known normal, symptom onset to consult, timing in the day, and consult duration. Logistic regression was performed as indicated by bivariate analysis. Results: Eight hundred and seventy-four telestroke evaluations were included in our analysis. Accurate diagnosis through teleneurological consultation was seen in 85% of which 532 were strokes (true positives) and 170 were mimics (true negatives). Sensitivity, specificity, PPV, NPV were 97.8, 82.5, 93.7 and 93.4%, respectively. LR+ and LR- were 5.6 and 0.03. AUC (95% CI) was 0.9016 (0.8749-0.9283). Stroke mimics were more common with younger age and female gender and in those with less vascular risk factors. LR revealed OR (95% CI) of misdiagnosis for female gender of 1.9 (1.3-2.9). Lower age and lower NIHSS score were other predictors of misdiagnosis. Conclusion: We report high diagnostic accuracy of the Ochsner Telestroke Program in discriminating stroke/TIA and stroke mimics, with slight tendency towards over diagnosis of stroke. Female gender, younger age and lower NIHSS score were associated with misdiagnosis.

Patient Perspectives With Telehealth Visits in Cardiology During COVID-19: Online Patient Survey Study.

BACKGROUND: The rise of COVID-19 and the issue of a mandatory stay-at-home order in March 2020 led to the use of a direct-to-consumer model for cardiology telehealth in Kentucky. Kentucky has poor health outcomes and limited broadband connectivity. Given these and other practice-specific constraints, the region serves as a unique context to explore the efficacy of telehealth in cardiology. OBJECTIVE: This study aims to determine the limitations of telehealth accessibility, patient satisfaction with telehealth relative to in-person visits, and the perceived advantages and disadvantages to telehealth. Our intent was two-fold. First, we wanted to conduct a rapid postassessment of the mandated overhaul of the health care delivery system, focusing on a representative specialty field, and how it was affecting patients. Second, we intend to use our findings to make suggestions about the future application of a telehealth model in specialty fields such as cardiology. METHODS: We constructed an online survey in Qualtrics following the Patient Assessment of Communication During Telemedicine, a patient self-report questionnaire that has been previously developed and validated. We invited all patients who had a visit scheduled during the COVID-19 telehealth-only time frame to participate. Questions included factors for declining telehealth, patient satisfaction ratings of telehealth and in-person visits, and perceived advantages and disadvantages associated with telehealth. We also used electronic medical records to collect no-show data for in-person versus telehealth visits to check for nonresponse bias. RESULTS: A total of 224 respondents began our survey (11% of our sample of 2019 patients). Our recruitment rate was 86% (n=193) and our completion rate was 62% (n=120). The no-show rate for telehealth visits (345/2019, 17%) was nearly identical to the typical no-show rate for in-person appointments. Among the 32 respondents who declined a telehealth visit, 20 (63%) cited not being aware of their appointment as a primary factor, and 15 (47%) respondents cited their opinion that a telehealth appointment was not medically necessary as at least somewhat of a factor in their decision. Both in-person and telehealth were viewed favorably, but in-person was rated higher across all domains of patient satisfaction. The only significantly lower mean score for telehealth (3.7 vs 4.2, P=.007) was in the clinical competence domain. Reduced travel time, lower visit wait time, and cost savings were seen as big advantages. Poor internet connectivity was rated as at least somewhat of a factor by 33.0% (35/106) of respondents. CONCLUSIONS: This study takes advantage of the natural experiment provided by the COVID-19 pandemic to assess the efficacy of telehealth in cardiology. Patterns of satisfaction are consistent across modalities and show that telehealth appears to be a viable alternative to in-person appointments. However, we found evidence that scheduling of telehealth visits may be problematic and needs additional attention. Additionally, we include a note of caution that patient satisfaction with telehealth may be artificially inflated during COVID-19 due to external health concerns connected with in-person visits.

Description of a novel telemedicine-enabled comprehensive system of care: drip and ship plus drip and keep within a system of stroke care delivery.

United States (US) and worldwide telestroke programs frequently focus only on emergency room hyper-acute stroke management. This article describes a comprehensive, telemedicine-enabled, stroke care delivery system that combines "drip and ship" and "drip and keep" models with a comprehensive stroke center primary hub at Ochsner Medical Center in New Orleans, advanced stroke-capable regional hubs, and geographically-aligned, "stroke-ready" spokes. The primary hub provides vascular neurology expertise via telemedicine and monitors care for patients remaining at regional hubs and spokes using a multidisciplinary team approach. By 2014, primary hub telestroke consults grew to ≈1000/year with 16 min average door to consult initiation and 20 min to completion, and 29% of ischemic stroke patients received recombinant tissue-type plasminogen activator (rtPA), increasing 275%. Most patients remained in hospitals close to home, but neurointensive care and interventional procedures were common reasons for primary hub transfer. Given the time sensitivity and expert consultation needed for complex acute stroke care delivery paradigms, telestroke programs are effective for fulfilling unmet care needs. Combining drip and ship and drip and keep management allows more patients to stay "local," limiting primary hub transfer unless more advanced services are required. Post admission telestroke management at spokes increases personnel efficiency and can positively impact stroke outcomes.

The Novel Methods for Analysis of Exosomes Released from Endothelial Cells and Endothelial Progenitor Cells.

Exosomes (EXs) are cell-derived vesicles that mediate cell-cell communication and could serve as biomarkers. Here we described novel methods for purification and phenotyping of EXs released from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads and fluorescence quantum dots (Q-dots®) techniques. EXs from the culture medium of ECs and EPCs were isolated and detected with cell-specific antibody conjugated microbeads and second antibody conjugated Q-dots by using nanoparticle tracking analysis (NTA) system. The sensitivities of the cell origin markers for ECs (CD105, CD144) and EPCs (CD34, KDR) were evaluated. The sensitivity and specificity were determined by using positive and negative markers for EXs (CD63), platelets (CD41), erythrocytes (CD235a), and microvesicles (Annexin V). Moreover, the methods were further validated in particle-free plasma and patient samples. Results showed that anti-CD105/anti-CD144 and anti-CD34/anti-KDR had the highest sensitivity and specificity for isolating and detecting EC-EXs and EPC-EXs, respectively. The methods had the overall recovery rate of over 70% and were able to detect the dynamical changes of circulating EC-EXs and EPC-EXs in acute ischemic stroke. In conclusion, we have developed sensitive and specific microbeads/Q-dots fluorescence NTA methods for EC-EX and EPC-EX isolation and detection, which will facilitate the functional study and biomarker discovery.

Analyses of Endothelial Cells and Endothelial Progenitor Cells Released Microvesicles by Using Microbead and Q-dot Based Nanoparticle Tracking Analysis.

Accurate analysis of specific microvesicles (MVs) from biofluids is critical and challenging. Here we described novel methods to purify and detect MVs shed from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads with fluorescence quantum dots (Q-dots) coupled nanoparticle tracking analysis (NTA). In the in vitro screening systems, we demonstrated that 1) anti-CD105 (EC marker) and anti-CD34 (EPC marker) conjugated-microbeads had the highest sensitivity and specificity for isolating respective MVs, which were confirmed with negative controls, CD41 and CD235a; 2) anti-CD144 (EC marker) and anti-KDR (EPC marker) conjugated-Q-dots exhibited the best sensitivity and specificity for their respective MV NTA detection, which were confirmed with positive control, anti-Annexin V (MV universal marker). The methods were further validated by their ability to efficiently recover the known amount of EC-MVs and EPC-MVs from particle-depleted plasma, and to detect the dynamical changes of plasma MVs in ischemic stroke patients, as compared with traditional flow cytometry. These novel methods provide ideal approaches for functional analysis and biomarker discovery of ECs- and EPCs- derived MVs.

Implementing telestroke to reduce the burden of stroke in Louisiana.

Cardiovascular diseases (heart diseases and stroke) are the leading cause of death in the United States. People living in rural areas have disproportionately high mortality rates due to stroke mainly due to lack of specialty services. Timely intervention is a critical factor in determining the prognosis for acute stroke and thousands of lives can be saved by recognizing/treating a stroke patient within an hour. This paper deals with telestroke, a unique intervention implemented in Louisiana that incorporated latest technology to integrate with advanced clinical protocols in treating acute stroke. People living in remote and rural areas of Louisiana were greatly benefited from this initiative and several lives saved as a result of timely intervention. Expanding these initiatives to larger populations and other states will greatly reduce the stroke mortality.

Topiramate-induced myoclonus and psychosis during migraine prophylaxis.

PURPOSE: A case of topiramate-induced myoclonus and acute psychosis in a patient taking the recommended dosage of topiramate for migraine prophylaxis is reported. SUMMARY: A 29-year-old Caucasian, wheelchair-bound woman with diplegic cerebral palsy and a history of migraines was admitted to the hospital after developing paranoid thoughts and episodes of myoclonus two weeks after an increase in her topiramate dosage (25 mg twice daily to 50 mg twice daily). Her physical examination upon admission was unremarkable, with the exception of a temperature of 38.2 degrees C. Diagnostic laboratory test values, including those of the cerebrospinal fluid, were within normal limits. During neurologic examination, arm jerking, lip smacking, and finger movements occurred spontaneously and unprovoked, and severe bilateral leg myoclonus with plantar stimulation was observed. The results of an ultrasound of her lower extremities and a computed tomography scan of the brain with and without contrast revealed no abnormalities. An electroencephalogram was taken and showed nothing unusual. After nonpharmacologic etiologies were ruled out, her topiramate dosage was decreased and discontinued over four days. Her mental status and myoclonus drastically improved. She was stable and discharged within 24 hours of topiramate discontinuation. Follow-up at six months revealed that her myoclonus had completely resolved. While she has experienced additional psychotic episodes, these were mild and appear to be related to her depression. Myoclonus has not returned. CONCLUSION: A patient with cerebral palsy experienced myoclonus and acute psychosis after receiving a standard dosage of topiramate for migraine prophylaxis.

Usefulness of electrodiagnostic techniques in the evaluation of suspected tarsal tunnel syndrome: an evidence-based review.

This evidence-based review was performed to evaluate the utility of nerve conduction studies (NCSs) and needle electromyography (EMG) in the diagnosis of tibial neuropathy at the ankle (tarsal tunnel syndrome, TTS). A total of 317 articles on TTS were identified that were published in English from 1965 through April 2002, from the National Library of Medicine MEDLINE database. All articles were reviewed on the basis of six selection criteria. The results of this search revealed that four articles met five or more criteria. All four articles examined the use of electrodiagnostic (EDX) techniques for the evaluation of patients with clinically suspected TTS, and were included in this practice parameter. Each of these four studies was considered to meet Class III level of evidence. NCSs were abnormal in some patients with suspected TTS. Sensory NCSs were more likely to be abnormal than motor NCSs but the actual sensitivity and specificity could not be determined. The sensitivity of needle EMG abnormalities could not be determined. NCSs may be useful for confirming the diagnosis of tibial neuropathy at the ankle, recommendation Level C. Well-designed studies are needed to evaluate more definitively EDX techniques in TTS.