Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.
Large vessel occlusion in patients on ECMO is challenging to appreciate clinically secondary to sedation or induced paralysis, thus placing more emphasis on neurovascular imaging. However, emergent CTA and CTP are both inaccurate and unreliable in ECMO patients due to altered circuitry and interference with normal physiologic hemodynamics. In this review, the utility of DSA is discussed in evaluating the altered hemodynamics of VA-ECMO circuits and patency of major vasculature. In addition, the potential use of TCD in ECMO patients is discussed.
The COVID-19 pandemic has reshaped the way healthcare systems operate around the world. The major hurdles faced have been availability of personal protective equipment, intensive care unit beds, ventilators, treatments and medical personnel. Detroit, Michigan has been an epidemic ‘hotspot’ in the USA with Wayne County among the hardest hit counties in the nation. The Department of Neurology at Henry Ford Hospital, in the heart of Detroit, has responded effectively to the pandemic by altering many aspects of its operations. The rapid engagement of the department and enhanced utilisation of teleneurology were two of the pivotal elements in the successful response to the pandemic. In this review, we describe the transformation our department has undergone, as it relates to its infrastructure redesigning, coverage restructuring, redeployment strategies, medical education adaptations and novel research initiatives.
68-year-old woman with a history of rheumatoid arthritis presented to the emergency department with 3 months of rapidly progressing cognitive decline. Examination revealed new short-term memory loss, poor attention, difficulty conceptualizing tasks and inability to complete multistep actions. Three days after admission, the patient developed limb rigidity, hyperreflexia, exaggerated startle response, and autonomic dysfunction with fluctuations in blood pressure and heart rate. Magnetic resonance imaging (MRI) of the patient's brain showed bilateral confluent hyperintense signal changes in the basal ganglia (Figure 1A). Autoimmune serology revealed positive antinuclear antibody at 1:640 (homogenous pattern; reference range < 1:80) and elevated cyclic citrullinated peptide antibody (> 340 IU/mL [reference range < 7 IU/mL]). Consistent with a diagnosis of seronegative autoimmune encephalitis, serology was negative for glutamic acid decarboxylase, N-methyl-D-aspartate receptor and glycine receptor antibodies. Cerebrospinal fluid analysis revealed only an elevated protein level of 203 mg/dL (normal range 15-55 mg/dL). Further long-chain fatty acid, toxic, infectious and neoplastic test results were negative (Appendix 1, available at www.cmaj.ca/lookup/ doi/10.1503/cmaj.200424/tab-related-content), and we diagnosed the patient with autoimmune encephalitis. The patient received a 1 g dose of methylprednisolone, after which gastrointestinal bleeding developed. Two weeks later, a repeat brain MRI showed interval worsening of findings (Figure 1B). She was treated with 5 rounds of plasmapheresis, after which a repeat brain MRI showed nearly complete resolution of basal ganglia hyperintensity (Figure 1C). She received rituximab, and 6 weeks later she had made a full neurologic recovery. Autoimmune encephalitis has an incidence of 5-10 per 100 000 person-years. 1 Diagnosis is based on the clinical presentation of progressive encephalomyelitis and neuroimaging findings suggestive of encephalitis. 1,2 Negative antibody test results do not exclude autoimmune encephalitis, and there is an
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