Seronegative acute encephalitis following COVID-19 vaccines: a case series of an overlooked diagnosis with literature review.

PURPOSE: Autoimmune encephalitis is a neurological emergency of new-onset altered mental status, caused by an exaggerated immune-mediated response that targets the central nervous system. Autoimmune encephalitis has become an emerging differential diagnosis, when a classical infection cannot explain neurological symptoms. Displaying overlapping clinical presentations, ranging from the insidious onset of cognitive deficiency to more severe forms of encephalopathy with refractory seizures, autoimmune encephalitis can be challenging for clinicians. When evidence of malignancy is absent and pathogenic autoantibodies are undetected, with typical clinical and imaging features of autoimmune encephalitis, seronegative autoimmune encephalitis may be considered. Recently, vaccination-related autoimmune encephalitis and acute encephalitis after COVID-19 vaccination have attracted attention. METHODS AND RESULTS: We report a case series consisting of three patients with autoimmune encephalitis occurring shortly after COVID-19 vaccination and a current review of all previous reported autoimmune encephalitis related to COVID-19 vaccines. CONCLUSION: We emphasise on the prompt diagnosis of autoimmune encephalitis induced by Covid-19 vaccines and its timely treatment to improve the clinical outcome of this severe neurological condition. Post-licencing vaccine safety surveillance for potential adverse events is essential for vaccine safety and public confidence.

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Encephalitis Associated With SARS-CoV-2 Infection in a Child With Chiari Malformation Type I.

BACKGROUND/AIM: There is increasing evidence that patients infected with SARS-CoV-2 develop neurological manifestations such as encephalitis. The purpose of this article was to present a case of viral encephalitis associated with SARS-CoV-2 in a 14-year-old child with Chiari malformation type I. CASE REPORT: The patient manifested frontal headache, nausea, vomiting, skin pallor, right side Babinski sign and was diagnosed with Chiari malformation type I. He was admitted with generalized seizures and suspected encephalitis. Brain inflammation and viral RNA in the cerebrospinal fluid suggested SARS-CoV-2 encephalitis. These findings indicate that the SARS-CoV-2 test in CSF of patients with neurological manifestations, confusion, and fever during the COVID-19 pandemic should be carried out even when there is no evidence of respiratory infection. To our knowledge, this presentation of encephalitis associated with COVID-19 has not yet been reported in a patient with a congenital syndrome such as Chiari malformation type I. CONCLUSION: Further clinical data are needed to determine the complications of encephalitis due to SARS-CoV-2 in patients with Chiari malformation type I to standardize diagnosis and treatment.

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Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since the end of 2019. There is an increasing number of reports on nervous system symptoms, among which encephalitis is considered a serious neurological complication of COVID-19, but there are few reports of this complication in China. Acute encephalitis has severe symptoms. If it is not identified early and treated in time, the mortality is high and the prognosis is poor. During the current global epidemic, it is necessary to pay attention to the severe nervous system symptoms of COVID-19. Therefore, this article summarizes the clinical features of COVID-19 complicated by acute encephalitis through literature review and a detailed analysis of medical records, so as to provide a reference for clinicians to deal with the cases of COVID-19 complicated by acute encephalitis.

Brain stem encephalitis is a rare complication of COVID-19.

Here, we describe the clinical phenotype of SARS-CoV-2-related CNS disease and evaluate the SARS-CoV-2 antibody index as a tool to differentiate between a direct (viral) and indirect etiology. Out of >4000 hospitalized patients with COVID-19, we included 13 patients with neurological symptoms with suspicion of neuroinflammation. On clinical grounds, eight were classified as having a possible/probable relationship between neurological symptoms and COVID-19. A clinically distinctive phenotype of brainstem and cerebellar symptoms was seen in 6/8 patients. As we found a positive SARS-CoV-2 antibody index in 3/5 patients, indicating specific intrathecal SARS-CoV-2 IgG production, a direct link with SARS-CoV-2 is likely.

Autoimmune encephalitis after BBIBP-CorV (Sinopharm) COVID-19 vaccination: a case report.

BACKGROUND: Vaccination is an important public health strategy; however, many neurological adverse effects are associated with COVID-19 vaccination, being encephalitis a rare manifestation. CASE PRESENTATION: We present the case of a 33-year-old woman who received the first dose of the BBIBP-CorV vaccine against COVID-19 on April 4 and the second dose on April 28, 2021. Three days after receiving the second dose, she experienced a subacute episode of headache, fever, insomnia, and transient episodes of environment disconnection. We obtained negative results for infectious, systemic, and oncological causes. Brain magnetic resonance imaging showed lesions in the bilateral caudate nucleus and nonspecific demyelinating lesions at the supratentorial and infratentorial compartments. The results of the neuronal autoantibodies panel were negative. She had an adequate response to immunoglobulin and methylprednisolone; however, she experienced an early clinical relapse and received a new cycle of immunosuppressive treatment followed by a satisfactory clinical evolution. CONCLUSIONS: We report the first case of severe encephalitis associated with BBIBP-CorV (Sinopharm) vaccination in Latin America. The patient had atypical imaging patterns, with early clinical relapse and a favorable response to corticosteroid therapy.

[Neurological Manifestations of COVID-19: Meningoencephalitis and Encephalopathy].

Coronavirus disease (COVID-19) causes neurological symptoms in a high percentage of patients and is associated with various types of encephalitides and encephalopathies, which are etiologically classified into (a)direct infection of the central nervous system with severe acute respiratory syndrome coronavirus 2 and resultant meningoencephalitis (this is a rare presentation), (b)COVID-19-induced cytokine storms, which trigger endothelial cell injury, blood-brain barrier disruption, and microangiopathy and consequent encephalopathy and, (c)autoimmune encephalitis secondary to para- or post-infectious mechanisms that play a key role during the acute or post-COVID-19 phase. Notably, some patients present with neurological symptoms as the first manifestation. Radiologically characteristic encephalitides and encephalopathies, such as acute necrotizing encephalopathy, acute disseminated encephalomyelitis, posterior reversible encephalopathy syndrome, and clinically mild encephalitis/encephalopathy with a reversible splenial lesion are also complicated by COVID-19. Further investigations and appropriate treatments are warranted in patients with COVID-19, who develop new neurological symptoms.

Diagnosis and analysis of unexplained cases of childhood encephalitis in Australia using metatranscriptomic sequencing.

Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing ('metatranscriptomics') to determine the presence and abundance of potential pathogens, and to describe the possible aetiologies of unexplained encephalitis. Using this protocol, we identified five RNA and two DNA viruses associated with human infection from both non-sterile and sterile sites, which were confirmed by PCR. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases. Immune-mediated encephalitis was considered likely in six cases and metatranscriptomics did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasizes the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that non-central-nervous-system sampling in encephalitis clinical guidelines and protocols could improve the diagnostic yield.

Clinical symptoms, diagnosis, treatment, and outcome of COVID-19-associated encephalitis: A systematic review of case reports and case series.

INTRODUCTION: Since COVID-19 outbreak, various studies mentioned the occurrence of neurological disorders. Of these, encephalitis is known as a critical neurological complication in COVID-19 patients. Numerous case reports and case series have found encephalitis in relation to COVID-19, which have not been systematically reviewed. This study aims to evaluate the clinical symptoms, diagnosis, treatment, and outcome of COVID-19-associated encephalitis. METHODS: We used the Pubmed/Medline, Embase, and Web of Science databases to search for reports on COVID-19-associated encephalitis from January 1, 2019, to March 7, 2021. The irrelevant studies were excluded based on screening and further evaluation. Then, the information relating diagnosis, treatment, clinical manifestations, comorbidities, and outcome was extracted and evaluated. RESULTS: From 4455 initial studies, 45 articles met our criteria and were selected for further evaluation. Included publications reported an overall number of 53 COVID-19-related encephalitis cases. MRI showed hyperintensity of brain regions including white matter (44.68%), temporal lobe (17.02%), and thalamus (12.76%). Also, brain CT scan revealed the hypodensity of the white matter (17.14%) and cerebral hemorrhages/hemorrhagic foci (11.42%) as the most frequent findings. The IV methylprednisolone/oral prednisone (36.11%), IV immunoglobulin (27.77%), and acyclovir (16.66%) were more preferred for COVID-19 patients with encephalitis. From the 46 patients, 13 (28.26%) patients were died in the hospital. CONCLUSION: In this systematic review, characteristics of COVID-19-associated encephalitis including clinical symptoms, diagnosis, treatment, and outcome were described. COVID-19-associated encephalitis can accompany with other neurological symptoms and involve different brain. Although majority of encephalitis condition are reversible, but it can lead to life-threatening status. Therefore, further investigation of COVID-19-associated encephalitis is required.

Central nervous system adverse events after ChAdOx1 vaccination.

INTRODUCTION: Post-ChAdOx1 vaccine (AZD1222) adverse events following immunization (AEFI) are uncommon. Recently described neurological events include thrombocytopenia with thrombosis syndrome (TTS) with cerebral venous thrombosis and Guillain-Barré syndrome. There are very few AEFI reports following COVID vaccination from India, because of underreporting or other factors. A few cases of acute transverse myelitis (ATM) and post-vaccinal encephalitis have also been reported. MATERIALS AND METHODS: Over 11 months, in 2 districts of Kerala, India, 8.19 million people were vaccinated with the ChAdOx1 vaccine. RESULTS: During this period, we encountered five cases of autoimmune central nervous system (CNS) AEFI following ChAdOX1 (Oxford/AstraZeneca, Covishield™) vaccination. These included three cases of acute disseminated encephalomyelitis (ADEM), one case of opsoclonus myoclonus ataxia syndrome (OMAS), and one case of limbic encephalitis. The calculated crude incidence of post-ChAdOX1 autoimmune CNS AEFI was approximately 0.24 cases per million for encephalitis and 0.36 per million for ADEM. This was compared to the crude annual incidence of community-acquired ADEM worldwide (3.2-4 per million) and the crude annual incidence of community-acquired encephalitis in India (8.35-10 per million). CONCLUSION: There was no increase in the incidence of post-vaccination CNS AEFI (ADEM or encephalitis) as compared to the community incidence of ADEM or encephalitis. While this emphasizes the safety of ChAdOX1 nCoV-19 vaccination for COVID-19, it is important to recognize these post-vaccination autoimmune syndromes early to initiate immunosuppressive therapy.

Nervous system involvement after infection with COVID-19 and other coronaviruses.

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

A case of encephalitis following COVID-19 vaccine.

We describe the first case of encephalitis following coronavirus disease 2019 (COVID-19) vaccination. Our patient was a 46-year-old Japanese woman who presented with acute onset diplopia. Subsequent magnetic resonance imaging revealed brain stem encephalitis that was rapidly responsive to high dosage steroid therapy and completely improved. Although the occurrence of encephalitis after vaccination could have just been a casual temporal association, her symptoms were temporally correlated with two vaccinations. Our case suggests caution and indicates treatment and prognosis, despite no evidence of a causal relationship. Nonetheless, this report emphasizes the enormous benefits of vaccination, which should not be undermined.

Encephalitis as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes, and predictors.

BACKGROUND AND PURPOSE: Although COVID-19 predominantly affects the respiratory system, recent studies have reported the occurrence of neurological disorders such as stroke in relation to COVID-19 infection. Encephalitis is an inflammatory condition of the brain that has been described as a severe neurological complication of COVID-19. Despite a growing number of reported cases, encephalitis related to COVID-19 infection has not been adequately characterised. To address this gap, this systematic review and meta-analysis aims to describe the incidence, clinical course, and outcomes of patients who suffer from encephalitis as a complication of COVID-19. METHODS: All studies published between 1 November 2019 and 24 October 2020 that reported on patients who developed encephalitis as a complication of COVID-19 were included. Only cases with radiological and/or biochemical evidence of encephalitis were included. RESULTS: In this study, 610 studies were screened and 23 studies reporting findings from 129,008 patients, including 138 with encephalitis, were included. The average time from diagnosis of COVID-19 to onset of encephalitis was 14.5 days (range = 10.8-18.2 days). The average incidence of encephalitis as a complication of COVID-19 was 0.215% (95% confidence interval [CI] = 0.056%-0.441%). The average mortality rate of encephalitis in COVID-19 patients was 13.4% (95% CI = 3.8%-25.9%). These patients also had deranged clinical parameters, including raised serum inflammatory markers and cerebrospinal fluid pleocytosis. CONCLUSIONS: Although encephalitis is an uncommon complication of COVID-19, when present, it results in significant morbidity and mortality. Severely ill COVID-19 patients are at higher risk of suffering from encephalitis as a complication of the infection.

COVID-19-associated immune-mediated encephalitis mimicking acute-onset Creutzfeldt-Jakob disease.

We report a subtype of immune-mediated encephalitis associated with COVID-19, which closely mimics acute-onset sporadic Creutzfeldt-Jakob disease. A 64-year-old man presented with confusion, aphasia, myoclonus, and a silent interstitial pneumonia. He tested positive for SARS-CoV-2. Cognition and myoclonus rapidly deteriorated, EEG evolved to generalized periodic discharges and brain MRI showed multiple cortical DWI hyperintensities. CSF analysis was normal, except for a positive 14-3-3 protein. RT-QuIC analysis was negative. High levels of pro-inflammatory cytokines were present in the CSF and serum. Treatment with steroids and intravenous immunoglobulins produced EEG and clinical improvement, with a good neurological outcome at a 6-month follow-up.