Onset Refractory Status Epilepticus Research Articles

Using magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy to lateralize a seizure focus for staged surgical approach

New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prompting a workup for epilepsy surgery. Because NORSE remains etiologically elusive in most cases, surgical evaluations are challenging, especially when the epileptogenic zone (EZ) is not easy to lateralize as can be seen in frontal lobe seizures. Lateralizing a frontal lobe EZ may be challenging due to bilateral synchrony from commissural connections through the corpus callosum and low spatiotemporal resolution of the scalp electroencephalography (EEG). We report a pediatric patient with NORSE presenting with focal impaired awareness seizures clustering into super refractory status epilepticus (SRSE). She required surgical intervention for the treatment of her seizures after failing therapeutic doses of antiseizure medications, anesthetic drips, immunomodulation with methylprednisolone, intravenous immunoglobulin and anakinra, and the ketogenic diet. Despite her semiology being focal, the seizures were not well lateralized on scalp EEG and during phase 2 stereo-EEG (sEEG). Anterior magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy (MRgLITT CC) was performed in a multistage surgical approach to successfully lateralize the EZ with a left-lateralized ictal pattern seen after reimplantation of sEEG electrodes. Our case suggests that minimally invasive MRgLITT CC can be successfully used to lateralize an EZ in frontal lobe epilepsy and that epilepsy surgery should be considered in patients with NORSE with SRSE. We also demonstrate that laser interstitial thermal therapy (LITT), while not always resulting in seizure freedom, can sufficiently disrupt a network to abort status epilepticus and lead to seizure improvements.

FADD gene pathogenic variants causing recurrent febrile infection-related epilepsy syndrome: Case report and literature review.

FIRES and NORSE are clinical presentations of disease processes that, to date, remain unexplained without an established etiology in many cases. Neuroinflammation is thought to have paramount importance in the genesis of these conditions. We hereby report the clinical, EEG, brain MRI, and genetic findings of a nuclear family with recurrent febrile-related encephalopathy with refractory de novo Status Epilepticus. Whole-exome sequencing (WES) revealed a homozygous p.C105W pathogenic variant of FADD gene (FAS-associated protein with death domain, FADD), known to cause ultrarare forms of autosomal recessive immunodeficiency that could be associated with variable degrees of lymphoproliferation, cerebral atrophy, and cardiac abnormalities. The FADD-related conditions disrupt FAS-mediated apoptosis and can cause a clinical picture with the characteristics of FIRES. This observation is important because, on one hand, it increases the number of reported patients with FADD deficiency, showing that this disorder may present variable expressivity, and on the other hand, it demonstrates a genetic cause of FIRES involving a cell-mediated inflammation regulatory pathway. This finding supports early treatment with immunomodulatory therapy and could represent a new avenue of research in the field of new onset refractory status epilepticus and related conditions.

NORSE seasonality may vary geographically in adults.

The mechanisms causing new onset refractory status epilepticus (NORSE) are often unknown. Recently, a seasonal variation with NORSE peaking during the summer was described in a mixed cohort of adults and children why we here studied the seasonal variation in a Danish status epilepticus (SE) cohort. This retrospective cohort study comprised SE patients aged ≥18 diagnosed and treated 2008-2017 at the Odense University Hospital. Clinical characteristics and seasonality of patients fulfilling the diagnostic criteria for NORSE were compared with patients with refractory SE (RSE) due to other reasons and with the seasonal variation of autoantibodies associated with autoimmune encephalitis in the Danish autoimmune encephalitis register. In this cohort, 26 patients met NORSE criteria. As compared to RSE patients not fulfilling NORSE criteria (n = 152), NORSE patients were more likely to have symptoms of systemic inflammation (C-reactive protein concentrations ≥10 mg/L or fever ≥38°C) at admission; nine fulfilled the criteria for febrile infection related epilepsy syndrome (FIRES). In contrast to the even seasonal distribution of patients with RSE not fulfilling the NORSE criteria, admissions due to NORSE peaked during the winter (46.1%, p = 0.04 as compared to non-NORSE RSE); six out of nine FIRES episodes occurred in the winter season. The seasonal variation was not explained by a seasonal variation of the detection rates of autoantibodies associated with autoimmune encephalitis (incl. NMDAR, LGI1, CASPR2, GABAR, GFAP) in a Danish nationwide register (n = 259). In conclusion, we confirm the seasonality of NORSE in a Danish cohort, however, with a peak during winter suggesting a geographical variation not solely explained by autoimmune encephalitis associated with known autoantibodies. PLAIN LANGUAGE SUMMARY: The study investigated the seasonal patterns of new-onset refractory status epilepticus (NORSE), i.e. severe seizures that occur without an obvious cause and require very intensive treatment. In contrast to the previously observed peak frequency in summer, this Danish study found that NORSE cases peak in winter. Furthermore, the seasonal variation in NORSE cases was not found to be associated with autoimmune encephalitis caused by known autoantibodies. Together with the high rate of patients showing symptoms of systemic inflammation compared to other status epilepticus patients, the data suggest a link between misdirected immune system responses and NORSE. The study can therefore help in the further search for the currently unknown causes of NORSE.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

TBC1D24 Mutation Presenting as Post-partum New Onset Refractory Status Epilepticus (P7-1.003)

TBC1D24 Mutation Presenting as Post-partum New Onset Refractory Status Epilepticus (P7-1.003)

Long-term outcome in new onset refractory status epilepticus: a retrospective study

BackgroundNew onset refractory status epilepticus (NORSE) is a neurologic emergency without an immediately identifiable cause. The complicated and long ICU stay of the patients can lead to perceiving a prolongation of therapies as futile. However, a recovery is possible even in severe cases. This retrospective study investigates ICU treatments, short- and long-term outcome and ethical decisions of a case series of patients with NORSE.MethodsOverall, 283 adults were admitted with status epilepticus (SE) to the Neurocritical Care Unit of the University Hospital Zurich, Switzerland, between 01.2010 and 12.2022. Of them, 25 had a NORSE. We collected demographic, clinical, therapeutic and outcome data. Descriptive statistics was performed.ResultsMost patients were female (68%), previously healthy (Charlson comorbidity index 1 [0–4]) and relatively young (54 ± 17 years). 96% presented with super-refractory SE. Despite extensive workup, the majority (68%) of cases remained cryptogenic. Most patients had a long and complicated ICU stay. The in-hospital mortality was 36% (n = 9). The mortality at last available follow-up was 56% (n = 14) on average 30 months after ICU admission. The cause of in-hospital death for 89% (n = 8) of the patients was the withholding/withdrawing of therapies. Medical staff except for one patient triggered the decision. The end of life (EOL) decision was taken 29 [12–51] days after the ICU admission. Death occurred on day 6 [1–8.5] after the decision was taken. The functional outcome improved over time for 13/16 (81%) hospital survivors (median mRS at hospital discharge 4 [3.75–5] vs. median mRS at last available follow-up 2 [1.75–3], p < 0.001).ConclusionsOur data suggest that the long-term outcome can still be favorable in NORSE survivors, despite a prolonged and complicated ICU stay. Clinicians should be careful in taking EOL decisions to avoid the risk of a self-fulfilling prophecy. Our results encourage clinicians to continue treatment even in initially refractory cases.

Second-line immunotherapy in new onset refractory status epilepticus.

Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES). Consensus-driven recommendations have been established to guide the initiation of first- and second-line immunotherapies in these patients. Here, we review the literature to date on second-line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long-term disability and drug-resistant post-NORSE epilepsy. Initiation of second-line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post-NORSE epilepsy or long-term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes.

New onset refractory status epilepticus: Summary of the NORSE Institute roundtable during the 2023 American Epilepsy Society meeting, Orlando, Florida.

New onset refractory status epilepticus: Summary of the NORSE Institute roundtable during the 2023 American Epilepsy Society meeting, Orlando, Florida.

Reply to the article entitled “International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): Summary and clinical tools”. Doi: 10.1111/epi.17391

Reply to the article entitled “International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): Summary and clinical tools”. Doi: 10.1111/epi.17391

A - 94 A Case of New Onset Refractory Status Epilepticus (NORSE) Associated with COVID-19.

New Onset Refractory Status Epilepticus (NORSE) is a rare condition of prolonged medication-refractory seizures potentially due to elevated inflammatory molecules in the brain. NORSE can be triggered by a viral infection and is a documented neurologic consequence of COVID-19. A 74-year-old, left-handed, Hispanic male was in his usual state of health until experiencing 1-2weeks of speech decline, which culminated in an episode of altered mental status (disorientation and mumbling speech). He presented to the Emergency Department with drowsiness and complaints of a "funny feeling" on the left side of his head. Upon arrival, he was found to be COVID-19 positive and hyperglycemic with normal CT, MRI, lumbar puncture, and bloodwork. An EEG showed "focal temporal activity" and he was diagnosed with non-convulsant status epilepticus. Hospitalization and medical sedation lasted 2months followed by 8months of inpatient rehabilitation. The patient was discharged shortly before presenting for neuropsychological evaluation. Neuropsychological evaluation showed weaknesses in learning and free recall, visuospatial skills (due to disorganization and poor attention to details), processing speed, and executive functioning. The patient reported elevated anxiety symptoms. Collateral report indicated severe declines in executive organizational abilities, as well as mild memory and divided attention declines. Results suggest frontal cortical and subcortical impairments affecting multiple areas of cognition and functional decline consistent with a diagnosis of major neurocognitive disorder. Similar to the literature, status epilepticus was attributed to inflammatory meningoencephalitis triggered by the prior COVID-19 infection. Interdisciplinary care was an integral factor in this case.

A case of new onset refractory status epilepticus in a U.S. traveler with Japanese encephalitis

New onset refractory status epilepticus (NORSE) is a rare but critical condition characterized by refractory status epilepticus (RSE) in an individual without prior history of epilepsy or known structural, toxic, or metabolic cause. Postinfectious immune activation is an important cause of NORSE. Early testing for autoimmune antibodies is strongly recommended (Wickstrom et al., 2022). We report a case of NORSE triggered by Japanese encephalitis (JE) in an unvaccinated US adult traveler. Her CSF later revealed positive anti-N-methyl-d-aspartate (NMDA)-receptor antibody. The patient responded well to first line immunotherapy with favorable functional outcome. This case highlights the diagnostic and treatment challenges in this rare presentation.

NEW ONSET REFRACTORY STATUS EPILEPTICUS (NORSE): A CASE REPORT

New-onset refractory status epilepticus (NORSE) is rare and potential life-threatening neurological state where one develops status epileptic us without apparent aetiology. In the following case report, we see the management of NORSE (new onset of refractory status epilepticus) through standard guidelines in a patient with a history of CAD (coronary artery disease) with the risk-benet ratio. The management had a major risk of respiratory depression and heart failure and/or heart block, been given the age factor and the medical history of the patient and no known aetiology. Initiation of benzodiazepines and antiepileptic medication had a major impact on the patient, where the risk of heart block was high. The recovery of the patient was thoroughly monitored for 7 complete days. upon no further complaints the patient was then discharged. But the patient was stabilized by rst managing the NORSE and then treating the cardiac conditions.

A practical approach to in-hospital management of new-onset refractory status epilepticus/febrile infection related epilepsy syndrome.

New-onset refractory status epilepticus (NORSE) is "a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic, or metabolic cause." Febrile infection related epilepsy syndrome (FIRES) is "a subcategory of NORSE that requires a prior febrile infection, with fever starting between 2 weeks and 24 h before the onset of refractory status epilepticus, with or without fever at the onset of status epilepticus." These apply to all ages. Extensive testing of blood and CSF for infectious, rheumatologic, and metabolic conditions, neuroimaging, EEG, autoimmune/paraneoplastic antibody evaluations, malignancy screen, genetic testing, and CSF metagenomics may reveal the etiology in some patients, while a significant proportion of patients' disease remains unexplained, known as NORSE of unknown etiology or cryptogenic NORSE. Seizures are refractory and usually super-refractory (i.e., persist despite 24 h of anesthesia), requiring a prolonged intensive care unit stay, often (but not always) with fair to poor outcomes. Management of seizures in the initial 24-48 h should be like any case of refractory status epilepticus. However, based on the published consensus recommendations, the first-line immunotherapy should begin within 72 h using steroids, intravenous immunoglobulins, or plasmapheresis. If there is no improvement, the ketogenic diet and second-line immunotherapy should start within seven days. Rituximab is recommended as the second-line treatment if there is a strong suggestion or proof of an antibody-mediated disease, while anakinra or tocilizumab are recommended for cryptogenic cases. Intensive motor and cognitive rehab are usually necessary after a prolonged hospital stay. Many patients will have pharmacoresistant epilepsy at discharge, and some may need continued immunologic treatments and an epilepsy surgery evaluation. Extensive research is in progress now via multinational consortia relating to the specific type(s) of inflammation involved, whether age and prior febrile illness affect this, and whether measuring and following serum and/or CSF cytokines can help determine the best treatment.

GABA-A Receptor Meningoencephalitis presenting with New Onset Refractory Status Epilepticus and Reversible Vasculopathy (P4-5.002)

<h3>Objective:</h3> Discuss current clinical and neuroimaging phenotypes associated with GABA-A receptor encephalitis as applied to the case of a 14-year old female with a two-month history of behavior change and subsequent development of new onset refractory status epilpeticus and reversible vasculopathy. <h3>Background:</h3> Anti-Gamma Amino Butyric Acid-A (GABA-A) Receptor Encephalitis is an antibody mediated encephalitis which manifests with neurocognitive dysfunction, pharmacoresistant seizures, movement disorders, dysautonomia, and multifocal T2 FLAIR lesions in the cortex and subcortex without mass effect or enhancement. Not all patients fulfill these characteristics, creating challenges in early identification and treatment. <h3>Design/Methods:</h3> n/a <h3>Results:</h3> In this case we will discuss the current clinical and neuroimaging phenotypes associated with GABA-A receptor encephalitis cited in the literature and challenge their application to the case of a 14-year old female with a two-month history of behavior change and weight loss who was found to have serum and CSF positive anti-GABA-A receptor α1 subunit encephalitis. MRI showed persistent multifocal cortical/subcortical T2 changes during evaluation. Clinical course progressed from her initial behavioral changes to development of dysautonomia, new onset refractory status epilepticus (NORSE), and reversible vasculopathy. NORSE did not resolve until immunotherapy was escalated to apharesis and rituximab. Patient clinically improved and started cyclophosphamide for maintenance immunotherapy. <h3>Conclusions:</h3> GABA-A Receptor Encephalitis clinical features demonstrate progressive behavioral changes, dysautonomia, and new onset refractory status epilepticus. Radiographic features include persistent multifocal cortical/subcortical T2 changes. This case reinforces the previously described clinical and radiographic phenotypes of GABA-A receptor encephalitis, as well as the role of timely escalation of immunotherapy treatment. Further investigation is needed to observe the impact of primary immunodeficiency disorders and antibody mediated encephalitis disease. <b>Disclosure:</b> Dr. Garcia has nothing to disclose. Dr. Crowson has nothing to disclose. Dr. Angappan has nothing to disclose. Dr. Chen has received research support from OHSU Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD-Serono . The institution of Dr. Yadav has received research support from Department of Veterans Affairs. Dr. Yadav has received research support from NIH. Dr. Yadav has received research support from PCORI. Dr. Yadav has received research support from NMSS. The institution of Dr. Yadav has received research support from Department of Veterans Affairs. The institution of Dr. Yadav has received research support from Tykeson Family Foundation Endowed Professorship.

Treatment of new onset refractory status epilepticus/febrile infection-related epilepsy syndrome with tocilizumab in a child and a young adult.

New onset refractory status epilepticus (NORSE) is a rare and devastating condition occurring in a previously healthy patient. It is called febrile infection-related epilepsy syndrome (FIRES) when preceded by a febrile infection. It often leads to intensive care treatment, including antiseizure drugs in combination with anesthetic agents, and sometimes ketogenic diet. The mortality rate is high, and severe epileptic and neuropsychiatric sequelae are usually observed. Based on the possible role of neuroinflammation, intravenous immunoglobulin, corticosteroids, and immunomodulatory treatment (anti-IL1, IL6) can be added. We describe here a child and a young adult with FIRES, both treated with tocilizumab. We observed a rapid positive response on the status epilepticus and good tolerance, but different neurological outcomes for our two patients. Further prospective studies may be necessary both to confirm the efficacy and the safety of this promising treatment and to optimize the immunomodulatory strategy in FIRES/NORSE.

Inflammation as Treatment Target for Status Epilepticus.

Status epilepticus (SE) is a serious neurological disease that manifests as prolonged seizures that last more than 5 minutes and between such episodes, patients do not regain consciousness. It can result in cognitive defects, brain damage, or even death. It is commonly known that one of the causes can be an inflammatory process, but here we will focus on inflammation as a result of new onset refractory status epilepticus and, related to this, new promising forms of SE treatment. Particular emphasis has been focused on new-onset refractory status epilepticus (NORSE). Based on public research databases, drugs with anti-inflammatory activity - commonly used in different spheres of medicine - have been reviewed as potentially treating status epilepticus. There is seizable clinical research suggesting that drugs that decrease inflammatory processes might be effective in terminating status epilepticus. There is growing evidence showing that adding anti-inflammatory drugs to basic antiepileptic treatment enhances the efficiency of the therapeutic process, with special potential in NORSE cases.

Seizure burden and neuropsychological outcomes of new-onset refractory status epilepticus: Systematic review.

Long-term sequelae of the new onset refractory status epilepticus (NORSE) include the development of epilepsy, cognitive deficits, and behavioral disturbances. The prevalence of these complications has been previously highlighted in case reports and case series: however, their full scope has not been comprehensively assessed. We conducted a systematic review of the literature (PROSPERO ID CRD42022361142) regarding neurological and functional outcomes of NORSE at 30 days or longer following discharge from the hospital. A systematic review protocol was developed using guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Of the 1,602 records for unique publications, 33 reports on adults and 52 reports on children met our inclusion criteria. They contained the description of 280 adults and 587 children of whom only 75.7 and 85% of patients, respectively had data on long-term follow-up. The mean age of adult and pediatric patients was 34.3 and 7.9 years, respectively; and the longest duration of follow up were 11 and 20 years, respectively. Seizure outcomes received major attention and were highlighted for 93.4 and 96.6% of the adult and pediatric NORSE patients, respectively. Seizures remained medically refractory in 41.1% of adults and 57.7% of children, while seizure freedom was achieved in only 26 and 23.3% of these patients, respectively. The long-term cognitive outcome data was provided for just 10.4% of the adult patients. In contrast, cognitive health data were supplied for 68.9% of the described children of whom 31.9% were moderately or severely disabled. Long-term functional outcomes assessed with various standardized scales were reported in 62.2 and 25.5% of the adults and children, respectively with majority of patients not being able to return to a pre-morbid level of functioning. New onset psychiatric disorders were reported in 3.3% of adults and 11.2% of children recovering from NORSE. These findings concur with previous observations that the majority of adult and pediatric patients continue to experience recurrent seizures and suffer from refractory epilepsy. Moderate to severe cognitive disability, loss of functional independence, and psychiatric disorders represent a hallmark of chronic NORSE signifying the major public health importance of this disorder.

Autoimmune Encephalitis With Ganglionic a3-AChR Antibodies

Objective To describe a case of autoimmune encephalitis presented as new onset refractory nonconvulsive status epilepticus and autonomic failure caused by alpha-3 ganglionic acetylcholine receptor autoantibodies (a3-AChR Ab). Background Autoimmune autonomic ganglionopathy (AAG) is rare acquired dysautonomia in adults due to a3-AChR Ab. A patient typically presents with subacute autonomic dysfunction, and encephalitis has not been reported yet. Design/Methods NA. Results A 60 years old female presented with progressive worsening of mental status for two weeks. Vital signs were normal. The patient was somnolent, nonverbal, with tonic non-reactive pupils on the exam. CT head showed multiple subcortical hypodensities. MRI brain demonstrated T2-FLAIR hyperintense lesions in bifrontal lobes sparing the U-fibers, with abnormal leptomeningeal/pial perivenular type enhancement. MRI C/T spine, CT chest/Abd/pelvis were negative. Although serum and CSF testing showed inflammatory markers, meningoencephalitis and autoimmune encephalitis panel were negative, except for the serum Paraneoplastic panel was positive with high titer a3-AChR Abs. EEG showed nonconvulsive status epilepticus, which required management with three antiseizure medications. Initially, the patient had little response to empirical pulse methylprednisolone therapy. Later showed good clinical response with plasmapheresis. Later on she presented with nonobstructive small bowel obstruction, resolved with another pulse steroid therapy, discharged on dexamethasone taper. On a three-month follow-up, the patient was in near clinical remission, supported with resolved lesions on a repeat MRI. She never relapsed after two years of follow-up. Conclusions Studies have shown that a3-AChR Abs can result in diverse neurological manifestations, mainly dysautonomia. Our patient presented with encephalitis, dysautonomia, and refractory nonconvulsive status epilepticus. Scans suggested diffuse leukoencephalopathy, patient was found to have high 3-ACHR antibody seropositivity. Initially, the patient was steroid-resistant but showed clinical improvement with plasmapheresis. We have described an interesting case of encephalitis likely associated with a3-AChR Ab that has not been previously described. More studies are required to confirm this association.

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

AbstractMultisystem 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.

International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) incl. Febrile Infection-Related Epilepsy Syndrome (FIRES): Statements and Supporting Evidence.

To develop consensus-based recommendations for the management of adult and paediatric patients with NORSE/FIRES based on best evidence and experience. The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater or equal to 7, and inappropriate if the median score was less than or equal to 3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey. Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article. This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.