The Clinical Characteristics and Prognosis of Children Presenting with New Onset Refractory Status Epilepticus in COVID-19 Related Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory process leading to multiorgan failure and shock, occurring during the acute or post-infectious stage of severe acute respiratory syndrome coronavirus (SARS-CoV-2), and has two subtypes: para-infectious and post-infectious varieties. The new onset of refractory status epilepticus has rarely been described as the presenting feature of MIS-C. This retrospective study, conducted at Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, included children hospitalized between August 1, 2020 and July 31, 2021, with new-onset refractory status epilepticus (NORSE) and subsequently diagnosed to have MIS-C. Their clinico-demographic variables, treatment courses during hospital stays, laboratory reports, radiological and electrophysiological findings, and outcomes at discharge and follow-up over 1 year were recorded. At their 12 month visits, their motor disabilities (primary) and continuation of anti-epileptic drugs, and persistence of magnetic resonance imaging (MRI) brain abnormalities (secondary) were the outcome measures. The characteristics of the patients in the para-infectious and post-infectious groups were compared using the Mann-Whitney U test for continuous variables and the Chi-square test for categorical variables. There were eight and 10 patients in groups A and B, respectively. Patients in group B had significantly higher age, more prolonged refractory status epilepticus (RSE), use of anesthetics and ventilation, and longer pediatric intensive care unit (PICU) stay, while other clinical and laboratory parameters and short and long-term outcomes were not significantly different between the two groups. Eight patients developed hemiparesis, while two had quadriparesis in the acute stage, but 15 (83%) patients had complete recovery from their motor deficits by 1 year. At 1-year follow-up, 33 and 39% of patients, respectively, had abnormal MRI and electroencephalogram (EEG). Acute disseminated encephalitis and acute leukoencephalopathy were the most commonly observed MRI abnormalities in the acute phase, with prolonged persistence of cerebritis in patients in the post-infectious group, warranting long-term immunomodulation. Combined immunotherapy with intravenous immunoglobulin and steroids was effective in the acute phase. However, long-term anti-epileptic therapy was needed in both groups.

New-onset refractory status epilepticus after first dose of tozinameran

As the worldwide vaccination effort against COVID-19 gains traction, complications attributed to the vaccines are increasingly reported in medical literature. Herein, we describe the first two cases of new-onset refractory status epilepticus after receiving their first doses of tozinameran. These were attributed to underlying autoimmune responses against the vaccine given the temporal proximity to them receiving tozinameran, the absence of alternative diagnoses, the refractoriness of their seizures, and their clinical improvement only after administration of immunotherapies. Importantly, their cases supplement existing reports on the rare neurologic complications of the COVID-19 vaccines and encourage continued vigilance amongst the physicians amidst the pandemic. [ FROM AUTHOR] Copyright of Neurology Asia is the property of Association of South East Asian Nations, Neurological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

New-onset refractory status epilepticus due to autoimmune encephalitis after vaccination against SARS-CoV-2: First case report.

Background: Vaccination against SARS-CoV-2 has been conducted frequently to limit the pandemic but may rarely be associated with postvaccinal autoimmune reactions or disorders. Case presentation: We present a 35-year-old woman who developed fever, skin rash, and headache 2 days after the second SARS-CoV-2 vaccination with BNT162b2 (Pfizer/Biontech). Eight days later, she developed behavioral changes and severe recurrent seizures that led to sedation and intubation. Cerebral magnetic resonance imaging showed swelling in the (para-) hippocampal region predominantly on the left hemisphere and bilateral subcortical subinsular FLAIR hyperintensities. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis of 7 cells/µl and normal protein and immunoglobulin parameters. Common causes of encephalitis or encephalopathy such as viral infections, autoimmune encephalitis with well-characterized autoantibodies, paraneoplastic diseases, and intoxications were ruled out. We made a diagnosis of new-onset refractory status epilepticus (NORSE) due to seronegative autoimmune encephalitis. The neurological deficits improved after combined antiepileptic therapy and immunomodulatory treatment including high-dose methylprednisolone and plasma exchange. Conclusions: Although a causal relationship cannot be established, the onset of symptoms shortly after receiving the SARS-CoV-2 vaccine suggests a potential association between the vaccination and NORSE due to antibody-negative autoimmune encephalitis. After ruling out other etiologies, early immunomodulatory treatment may be considered in such cases.

New-Onset Refractory Status Epilepticus Secondary to COVID-19 Infection in Adults: A Systematic Review.

Background: New-onset refractory status epilepticus (NORSE) has been reported in the scientific literature as a phenomenon associated with the COVID-19 infection. Given the resurgence of the newer variants of COVID-19 added with its multi-system manifestations, this project was conducted to study the clinical picture of NORSE secondary to COVID-19 infection. Methods: Three electronic databases were searched using an extensive search strategy from November 2019 to December 2021. Patients reporting NORSE secondary to COVID-19 were included in this review. The status epilepticus severity score (STESS) was calculated by the study authors for individual patients. Statistical analysis was performed using SPSS version 26 with a p-value <0.05 as statistically significant. Results: After screening, 12 patients were included in this study with a mean age of 61.6 ± 19.0-year olds. The most common type of status epilepticus reported in our study population was non-convulsive status epilepticus (NCSE) (7 out of 12 patients, 58.3%). The linear regression model revealed that STESS scores were significantly influenced by patients' age (p = 0.004) and intra-hospital occurrence (IHO) of status epilepticus (p = 0.026). Overall, 8 patients (66.7%) were discharged without complications. Conclusion: Given the observed association of STESS with the aging population and IHO of status epilepticus, special attention is due to the caretakers of this population, while further studies are needed to further build upon this review.

Rapidly evolving Creutzfeldt-Jakob disease in COVID-19: from early status epilepticus to fatal outcome.

We report the case of a 70-year-old man coming to our attention for new onset refractory status epilepticus (NORSE) in a rapidly evolving CJD during SARS-CoV-2 co-infection. Our case report describes a fulminant CJD evolution associated with SARS-CoV-2 infection, which led to patient death after 15 days from admission. First EEG presented continuous diffuse spikes, sharp waves and sharp-and-slow wave complexes, pattern consistent with a non-convulsive status epilepticus (NORSE). Our case supports how CJD with SARS-CoV-2 co-infection could be characterized by an accelerated evolution, as already hypothesize for others microorganism infections, and how the diagnosis might be more challenging due to its uncommon presentations, such as NORSE.

New-onset refractory status epilepticus as an early manifestation of multisystem inflammatory syndrome in adults after COVID-19.

Multisystem inflammatory syndrome in adults (MIS-A) is a rare hyperinflammatory complication with multi-organ involvement that manifests a few weeks after recovering from a typically mild coronavirus disease 2019 (COVID-19) infection. Although encephalopathy and seizures can occur in the acute phase of COVID-19, the nervous system is infrequently involved in patients with MIS-A. Herein, we describe the case of a young woman who presented with new-onset refractory status epilepticus (NORSE) following a mild COVID-19 infection associated with symptoms, signs, and laboratory findings that satisfy the updated Centers for Disease Control and Prevention (CDC) definition of MIS-A. Magnetic resonance imaging of the brain revealed symmetric T2-signal increase involving both orbitofrontal lobes, insulae, and hippocampi. One of the notable findings in our patient was the quick response and significant clinical recovery that occurred following initiation of treatment with intravenous methylprednisolone and intravenous immunoglobulin. Our case expands the clinical spectrum of MIS-A and documents the occurrence of NORSE as one of its early clinical manifestations. A routine comprehensive clinical and laboratory assessment is needed to screen for this underdiagnosed condition, especially in patients with post-COVID-19 inflammatory complications.

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies.

BACKGROUND AND PURPOSE: New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions. METHODS: A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome. RESULTS: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called 'cryptogenic NORSE'. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described. CONCLUSIONS: Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE.

Intravenous immunoglobulin response in new-onset refractory status epilepticus (NORSE) COVID-19 adult patients.

Neurological manifestations may be common in COVID-19 patients. They may include several syndromes, such as a suggested autoimmune abnormal response, which may result in encephalitis and new-onset refractory status epilepticus (NORSE). Quickly recognizing such cases and starting the most appropriate therapy is mandatory due to the related rapid worsening and bad outcomes. This case series describes two adult patients admitted to the university hospital and positive to novel coronavirus 2019 (SARS-CoV-2) infection who developed drug-resistant status epilepticus. Both patients underwent early electroencephalography (EEG) assessment, which showed a pathological EEG pattern characterized by general slowing, rhythmic activity and continuous epileptic paroxysmal activity. A suspected autoimmune etiology, potentially triggered by SARS-CoV-2 infection, encouraged a rapid work-up for a possible autoimmune encephalitis diagnosis. Therapeutic approach included the administration of 0.4 g/kg intravenous immunoglobulin, which resulted in a complete resolution of seizures after 5 and after 10 days, respectively, without adverse effects and followed by a normalization of the EEG patterns.