Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients.

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.

BACKGROUND: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine. OBJECTIVE: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine. METHODS: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination. RESULTS: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome. CONCLUSION: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination.

Characterization and Analysis of Neurologic Adverse Events Associated with COVID-19 Vaccination

Objective: To characterize the incidence and spectrum of neurological adverse events (AE) after COVID-19 vaccination. Background: The devastating COVID-19 pandemic has led to 230 million people diagnosed and greater than 4.8 million deaths worldwide. Widespread vaccination efforts have resulted in administration of over 6 million vaccine doses to curb the significant health and socioeconomic impacts of the disease. While there are numerous reports of adverse events following COVID-19 vaccine, there is limited characterization of the spectrum of neurological AEs post-vaccination. Design/Methods: Data was gathered from the publicly available Vaccine Adverse Event Reporting System (VAERS), a passive reporting system not implying causality. Among individuals who received the J&J, Moderna, and Pfizer vaccines from 1/1/2021-6/14/2021, 314,610 adverse events were reported and these were reviewed by Neurology trained clinicians to determine the presence of various neurological AEs (40 conditions coded). Results: 306,473,169 COVID vaccine dose were administered in the USA during the study period with 314,610 total AEs (0.10%) and 105,930 neurological AEs (0.03%) reported. J&J vaccine was associated with the most AEs (17,670, 0.15%), followed by Moderna (42656, 0.03%) and Pfizer (42267, 0.03%). On average more events were reported in women (71%) and a majority occurred after the first dose (54%). < 1 events were reported per million vaccine doses for serious neurological conditions such as Bell's palsy (0.0007%), Guillain-Barre syndrome (0.00009%), cerebral venous thrombosis (0.00005%), transverse myelitis (0.00003%), and acute disseminated encephalomyelitis (0.00006%). Overall neurological complications following vaccine were drastically lower than complications post-COVID infection (14-80%). Conclusions: Adverse neurological events following COVID-19 vaccination are extremely rare and significantly less common than adverse neurological effects following SARS-CoV-2 infection. Current evidence suggests that along with being up to 100,000 times more likely to experience a major complication from COVID infection vs. vaccine, the risk of neurological complication is up to 5000 times more likely from infection itself.

The Spectrum of Neuro-COVID: A Study of a Comprehensively Investigated Large Cohort from India.

Background: Though reports of neurological manifestations of COVID-19 have emerged from various parts of the world, the cohorts reported are from the West and mostly derived from electronic databases. Much remains unknown regarding neuro-COVID in developing countries. India is the second-worst affected country, and this study reports the neurological manifestations of COVID-19 in a comprehensively evaluated cohort. Objective: The aim of this study was to describe the range of neurological manifestations of COVID-19 in India with an emphasis on the risk factors, laboratory and imaging findings and short-term outcome. Methods: Retrospective review of hospital records of all confirmed COVID-19 patients with neurological manifestations, receiving inpatient care in two neurology referral hospitals were done. All demographic, clinical details, investigations, and treatment were analysed. Results: A total of 120 confirmed COVID-19 cases presenting with neurological symptoms were included. The mean age of illness and duration of illness was 48.03 ± 17.3 years and 10.9 ± 17.3 days respectively. New onset of neurological symptoms occurred in 100 cases while 20 patients had worsening of pre-existing neurological illness. Stroke was the commonest neurological disorder (43%), followed by encephalopathy (23%) and Guillain-Barre syndrome (10%). Other unusual neurological manifestations included new-onset headache (7%), seizures including denovo status epilepticus (5%) and meningo-encephalitis (5%). Nearly half of the patients had preceding COVID-19 symptoms. Poor outcome at discharge was seen in 40% and mortality occurred in 15%. Conclusion: Stroke and encephalopathy constitute the most common neurological manifestations. The absence of preceding COVID-19 symptoms in nearly half the cases is striking. Poor outcome was seen in nearly 50% despite early recognition and management.