Descriptive Analysis of Acute Ischemic Stroke in COVID-19 Patients Through The Course of COVID-19 Pandemic

Objective: To describe our initial institutional experience in the treatment of patients with COVID-19 presenting with acute ischemic stroke (AIS) during the initial and subsequent COVID-19 infection surges, including reporting long-term outcomes. Background: Acute stroke care has been negatively impacted and/or delayed during the initial outbreak of COVID-19 with subsequent improvement over time. We highlight challenges encountered in identification and investigative workup of these patients, treatment concerns, evolution of AIS characteristics and management from 2020 to 2021, effects of COVID-19 vaccination, and considerations for future investigations. Design/Methods: All consecutive patients with COVID-19 and AIS treated at our institution during the COVID-19 outbreak, between March 1, 2020 and August 31, 2021 were included. Due to consideration for differences in patient management early and later in the COVID-19, patients were categorized in two separate cohorts: 1) patients diagnosed with AIS during the initial peak of COVID-19 (March thru October 2020), and 2) subsequent surges in infection (November 2020 thru August 2021). Baseline demographics, clinical, imaging, and outcomes data were retrospectively determined. Results: Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). AIS mechanism was undetermined or due to multiple etiologies in most cases (n=20, 57%). Three patients from the second cohort each received one dose of an mRNA COVID-19 vaccine. Comparative analysis showed that patients in the later cohort had earlier AIS presentation, fewer stroke risk factors, more comprehensive workup, more defined stroke mechanisms, lower incidence of critical COVID-19 severity, and greater utilization of IV TPA. Despite these differences, AIS incidence, NIHSS, and overall outcomes were similar, with most patients experiencing worsening or static functional 3-month outcomes. Conclusions: Further studies should investigate outcomes beyond 3 months and their predictive factors, impact of completed vaccination course, and access to neurologic care.

Retrospective Multihospital Prevalence Study of COVID-19 Acute Neurological Manifestations

Objective: We aim to investigate the prevalence, characteristics and outcomes of COVID-19 patients with neurological manifestations Background: To date, SARS-CoV2 has infected 213 million population worldwide. It is a multisystem disease affecting primarily the respiratory system, but neurological manifestations have been increasingly described in the literature. Design/Methods: Consecutive patients diagnosed with SARS-CoV2 admitted to 5 hospitals in Detroit Medical Center from March 3rd, 2020-May 1st, 2020 were included. Basic demographics and clinical manifestations were included. Relevant laboratory findings and neuroimaging were reported. Results: 413 patients were included in the study. Patients' demographics were as follows: mean age-66 years, 212 (51%) male, 346 (87%) African-American. 219(53%) patients had neurological symptoms at presentation, 32 patients presented purely with neurological symptoms. Other symptoms at onset include-respiratory 312(76%), constitutional 250(61%) and gastrointestinal 104(25%). 121(29%) patients were admitted to ICU, mean days from admission to ICU was 3.14 days. Incidence of neurological presentations were as follows: Encephalopathy 191(46.25%), myalgia 51(12.35%), headache 27 (6.54%), vertigo 20 (4.84%), hypogeusia 14 (3.39%), anosmia 12 (2.9%), stroke 13(3.14%), seizure 11 (2.9%). For patients with encephalopathy, median GCS at the onset of encephalopathy was 13 with IQR4. 94 (49.21%) of these patients were admitted to ICU;53(27.75%) were without coexisting toxic, metabolic or hypoxic factors contributing to encephalopathy. For patients with stroke, 12 patients presented with acute ischemic stroke, 2 with hemorrhagic conversion and 1 patient had cerebral venous sinus thrombosis. Characteristics of stroke were as follows: 8-multiple vascular territory, 11-cryptogenic etiology, 3-concurrent thromboembolic event. Median D-dimer was 5.76mg/LFEU(IQR3.74) and fibrinogen 550mg/dl(IQR 2.1). 2 patients received thrombolysis and 1 underwent thrombectomy. Mortality was 77%, Modified Rankin Scale (MRS)at baseline was 0-2 and all except 1 patient had MRS of 4-6 on discharge. Conclusions: Neurological manifestation is common amongst patients with SARS-CoV-2. Presence of encephalopathy or stroke confers an increased risk of mortality and morbidity.

Meta-analysis of175 Patients with COVID-19 and Seizures, Status Epilepticus, or Cortical Myoclonus: An Individual Patient Data Analysis

Objective: To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature. Background: Seizure disorders in COVID-19 have been sparingly reported. Lack of large-scale studies create challenges in identifying clinically relevant associated factors. Design/Methods: Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus developing prior to or during hospitalization, with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases, based on severity of respiratory symptoms. Good outcome was defined as discharge without severe deficits, and/or return to near baseline. Results: A total of 105 studies reporting 175 patients (male 56.6%;mean age 47.9, SD 25.7) were included. Status epilepticus occurred in 44 patients (25.1%) and myoclonus in 38 (21.7%). Any seizure-like activity on electroencephalography (EEG) was noted in 53/102 patients (52.0%). Abnormal cerebrospinal fluid analysis was reported in 32/83 patients (38.6%). Most common underlying diagnosis was encephalitis (autoimmune or infectious) in 42/175 patients (24.0%), followed by infarct (15/175;8.6%) and intracerebral hemorrhage (ICH) (13/175;7.4%). The most common treatment was levetiracetam (92/130;70.8%). Overall, 106/160 patients (66.3%) had good outcomes while 24/156 died (15.4%). Encephalitis was associated with good outcomes (p=0.005). Severe COVID-19 was associated with more myoclonus, poor outcome, and mortality (all p<0.001), with a trend towards more EEG abnormalities (p=0.066). In multivariate regression, only severe COVID-19 was associated with reduced odds of good outcome (OR=0.095;p=0.006), and higher odds of mortality (OR=4.60, p=0.040). Conclusions: Encephalitis, infarct, and ICH are common underlying etiologies in COVID-19 patients with seizure disorders. Overall, most patients achieved good outcome, thus highlighting the necessity of aggressively treating seizures, and identifying any treatable underlying etiology. Future research should investigate long-term neurocognitive outcomes in COVID-19 patients with seizure disorders.

Spectrum of stroke manifestations in COVID-19 patients

Objective: The initial institutional experience in treatment of patients with COVID-19 and acute ischemic stroke (AIS) in Detroit, Michigan is presented. Background: Acute ischemic stroke (AIS) has been associated with COVID-19. Stroke care has been complicated due to delayed presentation and recognition. Design/Methods: Baseline demographic, clinical, and imaging data were retrospectively determined among patients with confirmed or suspected COVID-19 and AIS. Results: Eighteen patients with confirmed or suspected COVID-19 infection with AIS were identified from our cohort (mean age, 64.1 years;56% women). Stroke onset was frequently delayed after COVID-19 symptoms (mean, 31 days;50% presented >30 days). 94% had two or more vascular risk factors. Isolated encephalopathy was the lone presenting neurologic symptom in 33%. 50% were on anticoagulation (prophylactic and/or therapeutic) at the time of stroke onset, and CRP, D-dimer, and fibrinogen were consistently elevated. Infarcts involved multiple (56%), bilateral (44%), and/or large vascular territories (67%). Stroke mechanism was cardioembolic in 11%, other determined etiology in 6%, and cryptogenic or multiple in 83%. Outcomes were generally poor with few patients returning to independence and a 33% mortality (n=6). Conclusions: Most patients displayed abnormal coagulation laboratory measures and had multiple, bilateral and/or large vascular infarcts, despite anticoagulation, highlighting the potential intrinsic hypercoagulable and prothrombotic state of COVID-19. Although the rate of stroke in encephalopathic patients is undetermined, stroke should be strongly considered as a cause of encephalopathy in COVID-19 patients. Patients with a history of stroke may be at heightened risk for recurrent and increased severity of strokes. Sedation breaks for neurological exams, completion of stroke work, defining the timing and duration of anticoagulation and long term follow up should be strongly considered to improve patient outcome in the COVID-19 pandemic.

Acute Encephalopathy in COVID-19 patients Early Experience from an Inner-City Hospital

Objective: We aim to investigate the prevalence, characteristics and outcomes of COVID-19 patients with encephalopathy. Other neurological manifestations of COVID-19 were described. Background: SARS-CoV-2 has rapidly spread worldwide and has now affected more than 30 million people. Although respiratory symptoms are the primary clinical manifestations of COVID-19, neurological manifestations of COVID-19 are increasingly recognized. Encephalopathy is reported as a common neurological presentation of COVID-19. The characteristics of patients with COVID-19 associated encephalopathy, including potential confounding toxic/metabolic/hypoxic factors has not been explored. Design/Methods: We retrospectively reviewed all patients consulted to the neurology service at the Detroit Medical Centre, from March 3 , 2020 to May 1 2020 who were tested positive for SARS-COV2. Clinical and laboratory data were recorded. Characteristics of encephalopathic COVID-19 patients with or without confounders were compared. Statistical analysis was performed using SPSS. Results: 49 patients were included, 40 patients (81.6%) had encephalopathy, of whom 21 patients (52.5%) had no confounders. Most common confounders were hypoxia and uremia. Patients with confounders were more likely to have dementia at baseline (p=0.049), significantly elevated inflammatory markers-C-reactive protein (P=0.02), white blood cell count(p=0.019), Ddimer(p=0.015). They were also less likely to be discharged home (p=0.009). Overall mortality is high in patient with encephalopathy (65%). 5 patients had embolic strokes, 5 had new onset seizures and 2 patients had pleocytosis on cerebrospinal fluid examination. Conclusions: We found a high prevalence of COVID-19 associated encephalopathy, independent of confounders. COVID-19 associated encephalopathy can be attributed to stroke, seizure, meningoencephalitis or idiopathic. This early report is part of an ongoing study with a larger cohort of all COVID-19 patients that continue to be admitted to our center to investigate underlying etiological mechanisms of encephalopathy, including long-term follow up of these patients.