New-onset Refractory Status Epilepticus Research Articles

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.

The etiology and mortality of new-onset refractory status epilepticus (NORSE) in adults: A systematic review and meta-analysis.

New-onset refractory status epilepticus (NORSE) is a devastating neurological presentation. There is a paucity of large studies on NORSE as it is a relatively new clinical syndrome. The aim of this review was to summarize the etiologies and establish a mortality rate for NORSE. Two independent authors systematically searched the following electronic databases from January 1, 2005 April 20, 2021: PubMed, Embase, OVID, Scopus, Web of Science, "Clinicaltrials.gov," and the International Standard Randomised Controlled Trial Number (ISRCTN) registry. We included all primary research studies of NORSE in adults and excluded commentaries, reviews, pre-clinical studies, and pediatric populations. Etiology was extracted from all studies meeting eligibility criteria, whereas data relating to treatments, hospital stay, functional outcomes, and mortality were extracted from studies with sample size ≥5. We conducted a random-effects meta-analysis of mortality rate with meta-regression testing for significant covariates. Of 1482 studies, 109 case reports and case series met our criteria, comprising 395 cases of NORSE. The most common etiology was cryptogenic in 197 cases (49.9%), followed by autoimmune in 143 cases (36.2%). The pooled mortality rate was 22% (95% confidence interval 17%-27%; =15), with low heterogeneity ( =0%). Meta-regression revealed that year of study, treatment with ketogenic diet or immunotherapy, percentage of cryptogenic cases, and length of intensive care unit stay were not significant covariates for mortality. Common treatments included antiseizure medications (median 5), general anesthesia, and immunotherapy such as corticosteroids, intravenous immunoglobulin, and plasma exchange. Mean length of intensive care admission was 33.4 days, with 52% of cases diagnosed with epilepsy on discharge. Neurocognitive impairment was a common sequela of NORSE. NORSE is associated with a high mortality. Half of cases remain cryptogenic, which presents a diagnostic challenge. Future focus should be on elucidating the underlying neurobiology and determining the most effective therapeutic interventions.

Blood-brain barrier damage and new-onset refractory status epilepticus: an exploratory study using dynamic contrast-enhanced MRI.

To characterize the blood-brain barrier (BBB) dysfunction in patients with new-onset refractory status epilepticus (NORSE) using dynamic contrast-enhanced MRI (DCE-MRI). This study included three groups of adult participants: patients with NORSE, encephalitis patients without status epilepticus (SE), and healthy subjects. These participants were retrospectively included from a prospective DCE-MRI database of neurocritically ill patients and healthy subjects. The BBB permeability (Ktrans) in the hippocampus, basal ganglia, thalamus, claustrum, periventricular white matter, and cerebellum were measured and compared between these three groups. A total of 7 patients with NORSE, 14 encephalitis patients without SE, and 9 healthy subjects were included in this study. Among 7 patients with NORSE, only one had a definite etiology (autoimmune encephalitis), and the rest were cryptogenic. Etiology of encephalitis patients without SE included viral (n = 2), bacterial (n=8), tuberculous (n = 1), cryptococcal (n = 1), and cryptic (n = 2) encephalitis. Of these 14 encephalitis patients without SE, 3 patients had seizures. Compared to healthy controls, NORSE patients had significantly increased Ktrans values in the hippocampus (0.73 vs 0.02 × 10-3 /min, p = 0.001) and basal ganglia (0.61 vs 0.003 × 10-3 /min, p = 0.007) and a trend in the thalamus (0.24 vs 0.08 × 10-3 /min, p = 0.017). Compared to encephalitis patients without SE, NORSE patients had significantly increased Ktrans values in the thalamus (0.24 vs 0.01 × 10-3 /min, p = 0.002) and basal ganglia (0.61 vs 0.004 × 10-3 /min, p = 0.013). This exploratory study demonstrates that BBBs of NORSE patients were impaired diffusely, and BBB dysfunction in the basal ganglia and thalamus plays an important role in the pathophysiology of NORSE.

Cytokines in New-Onset Refractory Status Epilepticus Predict Outcomes.

The objective of this study was to investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with new-onset refractory status epilepticus (NORSE) to better understand the pathophysiology of NORSE and its consequences. Patients with NORSE (n=61, including n=51 cryptogenic), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES), were compared with patients with other refractory status epilepticus (RSE; n=37), and control patients without SE (n=52). We measured 12 cytokines/chemokines in serum or CSF samples using multiplexed fluorescent bead-based immunoassay detection. Cytokine levels were compared between patients with and without SE, and between the 51 patients with cryptogenic NORSE (cNORSE) and the 47 patients with a known-etiology RSE (NORSE n=10, other RSE n=37), and correlated with outcomes. A significant increase of IL-6, TNF-α, CXCL8/IL-8, CCL2, MIP-1α, and IL-12p70 pro-inflammatory cytokines/chemokines was observed in patients with SE compared with patients without SE, in serum and CSF. Serum innate immunity pro-inflammatory cytokines/chemokines (CXCL8, CCL2, and MIP-1α) were significantly higher in patients with cNORSE compared to non-cryptogenic RSE. Patients with NORSE with elevated innate immunity serum and CSF cytokine/chemokine levels had worse outcomes at discharge and at several months after the SE ended. We identified significant differences in innate immunity serum and CSF cytokine/chemokine profiles between patients with cNORSE and non-cryptogenic RSE. The elevation of innate immunity pro-inflammatory cytokines in patients with NORSE correlated with worse short- and long-term outcomes. These findings highlight the involvement of innate immunity-related inflammation, including peripherally, and possibly of neutrophil-related immunity in cNORSE pathogenesis and suggest the importance of utilizing specific anti-inflammatory interventions. ANN NEUROL 2023;94:75-90.

New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?

The gene MT-TF encodes the mitochondrial tRNA of phenylalanine (tRNAphe). Its variations have been described as extremely rare etiologies of a variety of mitochondrial phenotypes. By means of whole-exome sequencing (WES), we detected a novel likely causative MT-TF variant (m.610T>C) in a family presenting with a combined movement disorder and epilepsy phenotype. The variant was present at 97% heteroplasmy in the peripheral blood and in a homoplasmic state in skin fibroblast-derived DNA. The inaugural manifestation in the index patient was new-onset refractory myoclonic status epilepticus (NORSE) at the age of 29 years. Her son presented later with developmental regression and myoclonic epilepsy. On the beginning of valproate because of ongoing myoclonic seizures, the index patient developed a generalized brain edema requiring bilateral craniotomy. In the course of the disease, epileptic manifestations abated, and both patients developed a severe movement disorder phenotype with prominent spastic-dystonic features. Both patients did not display any further sign of mitochondrial disease. Our report expands the clinicogenetic background of tRNAphe disease spectrum and highlights pitfalls in the diagnostics and management of mitochondrial epilepsy. The present findings advocate the introduction of rapid genetic testing in the diagnostic flow chart of NORSE in adults.

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.

A case of cryptogenic new-onset refractory status epilepticus (NORSE) in which cerebrospinal fluid IL-6 was elevated with increased seizure frequency early in the disease: a case report

A 25-year-old male presented with clonic seizures three days following a fever. The patient developed status epilepticus and required mechanical ventilation and intravenous anesthesia. The patient's epileptic seizures persisted despite administering intravenous anesthesia and multiple anti-epileptic drugs. The clinical presentation in this case, without pre-existing relevant neurological disorder and an active structural, toxic, or metabolic cause in the acute phase, was compatible with new-onset refractory status epilepticus (NORSE). After immunotherapy, including intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin therapy, the epileptic discharge on electroencephalogram (EEG) decreased gradually, and mechanical ventilation was discontinued. Neversless the final outcome was poor. The patient's condition was finally diagnosed as cryptogenic NORSE. The IL-6 levels in the cerebrospinal fluid showed a significant increase between day 6 and 11 after onset, during which time there was a rapid escalation in seizure frequency on EEG. Considering this, IL-6 may be involved in the process of seizure exacerbation.

Anti-N-methyl D-aspartate receptor encephalitis presenting with the new-onset refractory status epilepticus

Anti-N-methyl D-aspartate receptor encephalitis presenting with the new-onset refractory status epilepticus

The Increased Interleukin-6 Levels Can Be an Early Diagnostic Marker for New-Onset Refractory Status Epilepticus

New-onset refractory status epilepticus (NORSE) is a condition defined as the occurrence of refractory status epilepticus in patients without active epilepsy and no other acute causes of seizure. Although there is evidence that immune-mediated pathogenesis has a pivotal role in the epileptogenesis of NORSE, the diagnosis of NORSE is usually made on the clinical observation because there is no established biological marker suggesting the diagnosis of NORSE. We recently encountered a NORSE patient who was successfully treated with immunotherapy including tocilizumab, an anti-interleukin-6 (IL-6) receptor monoclonal antibody, and the markedly increased levels of serum and cerebrospinal fluid IL-6 were the only laboratory abnormality during the early treatment of the patient.

Pearls & Oy-sters: Status Epilepticus and Cerebral Edema From Hyperammonemia Due to Disseminated Ureaplasma and Mycoplasma Species.

Nonhepatic hyperammonemia syndrome is a rare cause of neurologic dysfunction and cerebral edema and has most commonly been reported in posttransplant patients. Only recently has opportunistic infection with Ureaplasma species and Mycoplasma hominis been found to be key to the pathogenesis. We describe the cases of 3 immunosuppressed patients who developed hyperammonemia syndrome with new-onset refractory status epilepticus and diffuse cerebral edema. PCR was positive for M hominis in 1 patient and Ureaplasma parvum in the other 2. Despite early diagnostic suspicion and aggressive management with empirical antibiotics, seizure control, hypertonic saline, and ammonia elimination, none of our patients survived this life-threatening infection. Nonhepatic hyperammonemia and new-onset seizures can be presenting features of disseminated Ureaplasma species and M hominis infections in posttransplant patients. Immunosuppression in the absence of organ transplantation is likely sufficient to trigger this entity, as was the case in our third patient. When suspected, empiric combination antibiotics should be used due to high likelihood of resistance. The diagnostic test of choice is PCR. Patients with hyperammonemia syndrome associated with these infections typically have a poor prognosis. Early recognition and aggressive multimodal interventions may be key to ameliorating the high mortality and severe neurologic sequelae from this entity.

Early clinical features of new-onset refractory status epilepticus (NORSE) in adults

BackgroundThe aim of this study was to identify early clinical features of patients with new-onset refractory status epilepticus (NORSE) that could direct the treatment in the first days of hospitalisation.MethodsA retrospective cohort study of adult NORSE patients treated in the intensive care units of Helsinki University Hospital 2007-2018.ResultsWe found 19 adult NORSE patients who divided into three subgroups on the basis of their clinical features: viral encephalitis (n = 5, 26%), febrile infection-related epilepsy syndrome (FIRES) (n = 6, 32%) and afebrile NORSE (n = 8, 42%). FIRES and afebrile NORSE patients remained without confirmed etiology, but retrospectively two paraneoplastic and two neurodegenerative causes were suspected in the afebrile NORSE group.Viral encephalitis patients were median 64 years old (IQR 55-64), and four (80%) had prodromal fever and abnormal findings in the first brain imaging. FIRES patients were median 21 years old (IQR 19-24), all febrile and had normal brain imaging at onset. In the afebrile NORSE group, median age was 67 (IQR 59-71) and 50% had prodromal cognitive or psychiatric symptoms. FIRES patients differed from other NORSE patients by younger age (p = 0.001), respiratory prodromal symptoms (p = 0.004), normal brain MRI (p = 0.044) and lack of comorbidities (p = 0.011). They needed more antiseizure medications (p = 0.001) and anesthetics (p = 0.002), had a longer hospital stay (p = 0.017) and more complications (p < 0.001).ConclusionsAmong febrile NORSE patients, FIRES group was distinctive due to patients’ young age, prodromal respiratory symptoms and normal first brain imaging. These features should be confirmed by subsequent studies as basis for selecting patients for early intensive immunotherapy.

Surviving status epilepticus: The patient and family perspective

Awareness of the long-term outcomes of status epilepticus is key to understanding the condition overall. Maintaining ties with patients' families is vital to both obtaining better long-term patient outcomes and obtaining that elusive data on long-term conditions. Common language and linked infrastructure support these ties. This position is posed within the context of NORSE (new-onset refractory status epilepticus) and FIRES (febrile infection-related epilepsy syndrome). This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Autoimmune Encephalitis Misdiagnosis: A Review of Reported Cases

Objective To identify autoimmune encephalitis (AE) mimics and clinical features reported in the literature. Background Recent evidence suggesting that AE is as frequent as infectious encephalitis has increased awareness and testing for immune-mediated causes of neurological impairment. Consistent with this theme, several publications have focused on patients in whom a diagnosis of AE was initially overlooked. On the contrary, AE remains a rare diagnosis in clinical practice, opening up the possibility for symptoms, signs, and test findings associated with other etiologies to be misattributed to AE. Design/Methods Case reports published in PubMed in English language before 04/2022 were reviewed. Cases in whom AE was clearly suspected during the diagnostic work-up or misdiagnosed were included. Results A total of forty-five patients with a final diagnosis different from AE were included from 40 reports. Median age was 52 (range 5-86) years; 30/45 (67%) were male. Twenty-eight patients fulfilled the criteria for possible AE (62%), five for definite AE (11%), and twelve neither (27%). Features suggestive of AE were acute/subacute altered mental status (ranging from abnormal behavior to coma), (82%); new-onset refractory status epilepticus, (7%); CSF pleocytosis (42%) or oligoclonal bands (9%), and apparent response to immunotherapy (38%). In 26 cases, imaging corresponded to the anatomical classification of limbic encephalitis, 15 had one or more cortical/subcortical T2-abnormalities, one meningeal involvement, one brainstem involvement, and two had normal MRI. In 12 patients, clinically not relevant neural autoantibodies were detected in serum and/or CSF, including GAD, Anti-Zic4, CASPR2, VGKC, anti-N-type calcium channel antibody, anti-LGI1, and GQ1B. We identified four common AE mimic categories: neoplasms (15 patients), infectious diseases (9 patients), genetic diseases (9 patients), and neurodegenerative diseases (7 patients). Five patients had other etiologies. Conclusions Despite well-defined clinical diagnostic criteria, the misdiagnosis of AE encompasses atypical presentation of common disorders and less likely rare diagnoses.

GABABR IgG Associated Encephalitis: Clinical Presentations and Measures to Improve Diagnostic Assay Specificity

Objective To review the clinical/oncological presentations of gamma aminobutyric acid-B receptor (GABABR)-IgG and evaluate the clinical specificity of antibody testing methodologies. Background GABABR-IgG is an intermediate-risk paraneoplastic autoantibody commonly associated with encephalitis and/or seizures. Design/Methods GABABR-IgG positive patients tested at Mayo Clinic Neuroimmunology Laboratory were identified. Available archived sera were retested by cell-based assay (CBA) at 1:10 and 1:100 dilutions. Results 105 GABABR-IgG seropositive patients with clinical details were identified (females, n = 56; median age 63 [range 8-82]). Most patients had one of three anti-GABABR encephalitis/seizure presentations: focal-onset seizures with altered mental status (n = 39), new-onset refractory status epilepticus (NORSE [n = 23]) or rapidly progressive dementia (n = 14). Fifty-three of 72 patients (74%) with available data had associated malignancy, primarily small cell lung cancer (SCLC). Two P/Q type VGCC-IgG positive patients had isolated Lambert-Eaton Myasthenic Syndrome. Additionally, 27 patients presented with non-specific symptoms or alternate diagnoses (atypical presentation); none had underlying SCLC (13 with malignancy data). Most patients with anti-GABABR encephalitis/seizure presentations had GABABR-IgG detected in CSF (95%, 52/55; of 3 who were negative, 1 had NMDA-IgG and another AMPA-IgG and CRMP5-IgG) and/or GABABR-IgG detected by CBA in serum at a dilution of 1:100 (76%, 31/41). Five encephalitis/seizure patients with GABABR-IgG detected in CSF were CBA positive only at 1:10 dilution in serum. Forty-eight of 76 patients had samples positive on tissue IFA (serum = 17/42, CSF = 40/49). Among 27 patients with atypical presentations, most did not have GABABR-IgG CSF CBA positivity (91%, 21/23) and/or GABABR-IgG 1:100 serum titer by CBA (0/17). None of 27 cases were tissue IFA positive (serum = 0/27, CSF = 0/21). Conclusions GABABR-IgG is associated with autoimmune encephalitis/seizure presentations. Our study highlights the importance of evaluating CSF and testing serum at both 1:10 and 1:100 dilutions, as seropositivity at only the 1:10 dilution by CBA without CSF GABABR-IgG positivity has poor clinical specificity.

New-onset refractory status epilepticus (NORSE) in paediatric patients: causes, characteristics and outcomes

BackgroundNew-onset refractory status epilepticus (NORSE) refers to patients without a previous history of seizures who have refractory status epilepticus for at least 72 hours without an identified aetiology. Despite the...

Multi-proteomic Analysis Revealed Distinct Protein Profiles in Cerebrospinal Fluid of Patients Between Anti-NMDAR Encephalitis NORSE and Cryptogenic NORSE.

New-onset refractory status epilepticus (NORSE) is rare but intractable. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and cryptogenic etiologies are the two major causes of NORSE with distinct clinical features. To elucidate the underlying mechanisms, 6 patients with anti-NMDAR encephalitis NORSE and 5 with cryptogenic NORSE (C-NORSE) were enrolled. Five patients of cerebrovascular disorders were used as controls. Quantitative proteomic analysis of the cerebrospinal fluid (CSF) samples of the patients revealed 101 and 56 proteins were changed, respectively. The average fold-change of the upregulated proteins, namely up-proteomic score in this study, was positively correlated with the severity and prognosis of the diseases, including ICU stay (r = 0.9308, P = 0.0035 in NMDAR group; r = 0.8977, P = 0.0193 in C-NORSE group), mRS score at discharge (r = 0.9710, P = 0.0111 in NMDAR group; r = 0.7071, P = 0.2000 in C-NORSE group), and time taken for patients awaking from a coma (r = 0.8823, P = 0.0100 in NMDAR group; r = 0.7906, P = 0.2000 in C-NORSE group). Pathways involved in humoral immune response, wound healing, and epigenetic regulation of transcription were upregulated in anti-NMDAR encephalitis NORSE. Pathways of innate and lymphocyte mediated immune response, synaptic functions, ubiquitination, and cell apoptosis were up-regulated in C-NORSE, which was consistent with a mouse model of status epilepticus. Fc receptor and B cell mediated immunity signaling pathways were downregulated in C-NORSE. Immunome microarray analysis demonstrated high autoantibody targeting 48 proteins in CSF samples of anti-NMDAR encephalitis NORSE. While the reaction was kept at a very low level in C-NORSE. There is no significant difference in inflammatory cytokine level between each group. The level of IL-4 (r = 0.7435, P = 0.0451), IL-13 (r = 0.7643, P = 0.0384), IFN-γ (r = 0.7973, P = 0.0287) and TNF-α (r = 0.8598, P = 0.0141) in NMDAR group, and IL-6 (r = 0.8479, P = 0.0348), IL-8 (r = 0.9076, P = 0.0166) in C-NORSE group were positively correlated with the up-proteomic score. The present study suggests that the up-proteomic score of CSF could be a promising indicator for assessment of the severity of anti-NMDAR encephalitis NORSE and C-NORSE. The distinct CSF proteomes imply different pathogenic mechanisms of the two diseases, and immunotherapy strategies as well.

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.

Long-term outcomes after NORSE: Treatment with vagus nerve stimulation.

New-onset refractory status epilepticus (NORSE) is associated with high mortality, therapy-resistant epilepsy (TRE), and poor cognitive and functional outcomes. Some patients develop multifocal TRE, for whom surgery with a curative intention, is not an option. In these patients, vagus nerve stimulation (VNS) is performed as a palliative treatment. We report the long-term outcomes regarding seizure frequency, functional and cognitive outcome, and effectiveness of VNS in two patients with TRE as a consequence of NORSE. In the first patient with cryptogenic NORSE, VNS implantation occurred during the acute stage, probably contributing to the cessation of her status epilepticus. However, in the long-term follow-up, the patient persisted with daily multifocal seizures. In the second patient, VNS implantation was delayed to manage his epilepsy when the NORSE, ultimately due to autoimmune encephalitis, had resolved. During long-term follow-up, no reduction in seizure frequency was achieved. This evidence supporting the use of VNS in patients with TRE after NORSE warrants further investigation.

Parallel roles of neuroinflammation in feline and human epilepsies

Autoimmune encephalitis refers to a group of disorders characterised by a non-infectious encephalitis, often with prominent seizures and surface neuronal autoantibodies. AE is an important cause of new-onset refractory status epilepticus in humans and is frequently responsive to immunotherapies including corticosteroids, plasma exchange, intravenous immunoglobulin G and rituximab. Recent research suggests that parallel autoantibodies can be detected in non-human mammalian species. The best documented example is leucine-rich glioma-inactivated 1 (LGI1)-antibodies in domestic cats with limbic encephalitis (LE). In this review, we discuss the role of neuroinflammation and autoantibodies in human and feline epilepsy and LE.