Mimics account for almost half of hospital admissions for suspected stroke. Stroke mimics may present as a functional (conversion) disorder or may be part of the symptomatology of a neurological or ...medical disorder. While many underlying conditions can be recognized rapidly by careful assessment, a significant proportion of patients unfortunately still receive thrombolysis and admission to a high-intensity stroke unit with inherent risks and unnecessary costs. Accurate diagnosis is important as recurrent presentations may be common in many disorders. A non-contrast CT is not sufficient to make a diagnosis of acute stroke as the test may be normal very early following an acute stroke. Multi-modal CT or magnetic resonance imaging (MRI) may be helpful to confirm an acute ischaemic stroke and are necessary if stroke mimics are suspected. Treatment in neurological and medical mimics results in prompt resolution of the symptoms. Treatment of functional disorders can be challenging and is often incomplete and requires early psychiatric intervention.
This review aims to summarize the therapeutic advances and evidence in the medical management of acute ischemic stroke (AIS). Recent evidence comparing the efficacy and safety of tenecteplase (TNK) ...with alteplase for intravenous thrombolysis (IVT) in AIS will be highlighted. Recent advances and evidence on improving micro-circulation following endovascular procedures and neuroprotection will be reviewed.
A significant number of randomized control studies now support the use of tenecteplase for IVT in AIS. TNK 0.25 mg/kg single bolus is as effective and well tolerated as alteplase 0.9 mg/kg infusion for IVT in AIS. Evidence from randomized control trials (RCTs) has shown effective and well tolerated expansion of the therapeutic window of IVT in the wake-up stroke and up to 9 h after last seen well, using advanced neuroimaging with computed tomography perfusion/MRI. Early evidence suggests that intra-arterial alteplase may help improve microcirculation in patients with large vessel occlusion following successful thrombectomy. However, more trials are required to confirm the results. Similarly, early evidence from a recent RCT showed that remote ischemic conditioning confers potential neuroprotection and improves outcomes in AIS.
Converging evidence has demonstrated that for patients with ischemic stroke presenting at under 4.5 h from the onset, TNK is comparable to alteplase. These data along with the practical advantages of TNK have resulted in a shift to replace intravenous TNK as the standard for thrombolysis. Ongoing studies of IVT with TNK are focussed on defining the optimal dose, expanding the time window with multimodal imaging and defining the role of thrombolysis for bridging patients with stroke due to large vessel occlusion.
IMPORTANCE: The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or ...implantable loop recorder after an ischemic stroke are unknown. OBJECTIVE: To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018. INTERVENTIONS: Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months. RESULTS: Among the 300 patients who were randomized (median age, 64.1 years interquartile range, 56.1 to 73.7 years; 121 were women 40.3%; and 66.3% had a stroke of undetermined etiology with a median CHA2DS2-VASc congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category score of 4 interquartile range, 3 to 5), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% 95% CI, 4.0% to 17.3%; risk ratio, 3.29 95% CI, 1.45 to 7.42; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, −2.0% 95% CI, −6.6% to 2.6%), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% 95% CI, −1.8% to 1.8%), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% 95% CI, −3.2% to 3.2%), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events. CONCLUSIONS AND RELEVANCE: Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 days, resulted in a significantly greater proportion of patients with AF detected over 12 months. Further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02428140
The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians ...across a wide range of settings. The goal is to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations include those related to diagnostic testing, diet and lifestyle, smoking, hypertension, hyperlipidemia, diabetes, antiplatelet and anticoagulant therapies, carotid artery disease, atrial fibrillation, and other cardiac conditions. Notable changes in this sixth edition include the development of core elements for delivering secondary stroke prevention services, the addition of a section on cervical artery dissection, new recommendations regarding the management of patent foramen ovale, and the removal of the recommendations on management of sleep apnea. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographic barriers to ensure equity in access within a universal health care system.
Durable HIV-1 remission has been reported in a person who received allogeneic stem cell transplants (SCTs) involving CCR5 Δ32/Δ32 donor cells. Much of the reduction in HIV-1 burden following ...allogeneic SCT with or without donor cells inherently resistant to HIV-1 infection is likely due to cytotoxic graft-versus-host effects on residual recipient immune cells. Nonetheless, there has been growing momentum to develop and implement stem cell therapies that lead to durable long-term antiretroviral therapy (ART)-free remission without the need for SCT.
Most current research leverages gene editing techniques to modify hematopoietic stem cells which differentiate into immune cells capable of harboring HIV-1. Approaches include targeting genes that encode HIV-1 co-receptors using Zinc Finger Nucleases (ZFN) or CRISPR-Cas-9 to render a pool of adult or progenitor cells resistant to de-novo infection. Other strategies involve harnessing multipotent mesenchymal stromal cells to foster immune environments that can more efficiently recognize and target HIV-1 while promoting tissue homeostasis.
Many of these strategies are currently in a state of infancy or adolescence; nonetheless, promising preclinical and first-in-human studies have been performed, providing further rationale to focus resources on stem cell therapies.
In this study, we demonstrated the use of low-cost portable electroencephalography (EEG) as a method for prehospital stroke diagnosis. We used a portable EEG system to record data from 25 ...participants, 16 had acute ischemic stroke events, and compared the results to age-matched controls that included stroke mimics. Delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DBATR) and pairwise-derived Brain Symmetry Index (pdBSI) were investigated, as well as head movement using the on-board accelerometer and gyroscope. We then used machine learning to distinguish between different subgroups. DAR and DBATR increased in ischemic stroke patients with increasing stroke severity (p = 0.0021, partial η
= 0.293; p = 0.01, partial η
= 0.234). Also, pdBSI decreased in low frequencies and increased in high frequencies in patients who had a stroke (p = 0.036, partial η
= 0.177). Using classification trees, we were able to distinguish moderate to severe stroke patients and from minor stroke and controls, with a 63% sensitivity, 86% specificity and accuracy of 76%. There are significant differences in DAR, DBATR, and pdBSI between patients with ischemic stroke when compared to controls, and these effects scale with severity. We have shown the utility of a low-cost portable EEG system to aid in patient triage and diagnosis as an early detection tool.
Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or ...repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.
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