The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.

Quiz Ref ID Acute stroke thrombolytic treatment is time sensitive and is usually delivered with the coordination of prehospital care providers and neurologists, physicians, and nurses in the emergency department (ED). Based on data from a pooled analysis of major intravenous tissue plasminogen activator (IV-tPA) trials, benefit is greater with early IV-tPA administration.¹ Many patients are unable to obtain acute stroke treatment because of delays in presentation to the hospital. Studies^2-4 exploring prehospital delays in stroke care have revealed that only 15% to 60% of patients having a stroke are able to reach the hospital within 3 hours of symptom onset and demonstrated that this proportion has not decreased over the last 10 years. Recently, mobile stroke units have been shown to reduce the time to evaluation and thrombolysis in Germany.^5,6 These systems use an ambulance equipped with a computed tomography (CT) system and laboratory testing that brings personnel, including a neurologist, to the scene. Quiz Ref ID Unlike other mobile stroke treatment units (MSTUs), the Cleveland Clinic MSTU solely uses telemedicine for physician presence. Telemedicine allows the remote presence of medical expertise and has wide clinical applications, including the evaluation of patients with acute stroke, which has proven to be highly reliable compared with in-person assessment.^7-13 Two cost-effectiveness analyses of mobile stroke unit systems have suggested favorable economics, especially if the need for on-site expertise can be eliminated by relying on telemedicine.^14,15 We report our initial experience with and the feasibility of an MSTU in Cleveland, Ohio, including the use of telemedicine as a substitute for physician presence, and compare the time efficiency of stroke evaluation in EDs.

Optimal neurologic monitoring methods have not been characterized for patients on extracorporeal membrane oxygenation (ECMO). We assessed the feasibility of noninvasive multimodal neuromonitoring (NMN) to prognosticate outcome. In this prospective observational study, neurologic examinations, transcranial Doppler (TCD), electroencephalography (EEG), and somatosensory evoked potentials (SSEPs) were performed at prespecified intervals. Outcome at discharge was defined as favorable when modified Rankin Scale (mRS) 0–3; unfavorable when mRS >3. Of 20 patients (median age 60 years), 17 had TCDs, 13 had EEGs, and seven had SSEPs. With NMN, 17 (85%) were found to have neurologic complications. Fourteen (70%) had unfavorable outcomes. The unfavorable outcome was associated with absent EEG reactivity, coma, central cannulation, higher transfusion requirement, and higher Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Seven patients had both SSEPs and EEGs and exhibited intact N20 responses despite poor outcomes. Four of these seven showed absent EEG reactivity despite intact N20. Eighteen thromboembolic events were observed, 14 of which had positive microembolic signals (MESs) in TCD. All 10 patients with arterial-sided thrombotic events had positive MES. NMN caused no adverse effects. NMN during ECMO is feasible and found high neurologic complication rate. EEG and TCD showed potential for prognostication of neurologic outcome.

Objectives: Although acute brain injury is common in patients receiving extracorporeal membrane oxygenation, little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial extracorporeal membrane oxygenation support. Design: Retrospective analysis. Setting: Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017. Patients: Patients more than 18 years old supported with a single run of venoarterial extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Of 10,342 venoarterial extracorporeal membrane oxygenation patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke. Reported acute brain injury during venoarterial extracorporeal membrane oxygenation decreased from 10% to 6% in 5 years. Overall in-hospital mortality was 56%, but rates were higher when ischemic stroke and hemorrhagic stroke were present (76% and 86%, respectively). In multivariable analysis, lower pre-extracorporeal membrane oxygenation pH (adjusted odds ratio, 0.21; 95% CI, 0.09–0.49; p < 0.001), higher PO₂ on first day of extracorporeal membrane oxygenation (adjusted odds ratio, 1.01; 95% CI, 1.00–1.02; p = 0.009), higher rates of extracorporeal membrane oxygenation circuit mechanical failure (adjusted odds ratio, 1.33; 95% CI, 1.02–1.74; p = 0.03), and renal replacement therapy (adjusted odds ratio, 1.49; 95% CI, 1.14–1.94; p = 0.004) were independently associated with ischemic stroke. Female sex (adjusted odds ratio, 1.61; 95% CI, 1.16–2.22; p = 0.004), extracorporeal membrane oxygenation duration (adjusted odds ratio, 1.01; 95% CI, 1.00–1.03; p = 0.02), renal replacement therapy (adjusted odds ratio, 1.81; 95% CI, 1.30–2.52; p < 0.001), and hemolysis (adjusted odds ratio, 1.87; 95% CI, 1.11–3.16; p = 0.02) were independently associated with hemorrhagic stroke. Conclusions: Despite a decrease in the prevalence of acute brain injury in recent years, mortality rates remain high when ischemic and hemorrhagic strokes are present. Future research is necessary on understanding the timing of associated risk factors to promote prevention and management strategy.