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Objective: New‐onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%–50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well‐phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers. Methods: Well‐characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005–2019. Treating epileptologists reported on post‐NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post‐discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome. Results: Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow‐up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes. Significance: Among survivors of cryptogenic NORSE, longer‐term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Differentiating status epilepticus (SE) from prolonged psychogenic nonepileptic seizures (pPNES) can be difficult clinically. We aimed to define the utility of peripheral cell counts, cell ratios, and lactate levels in distinguishing SE from pPNES. Methods: Retrospective two‐center study investigating the sensitivity and specificity of acute (≤12 h of event offset) peripheral cell counts, cell ratios (neutrophil–lymphocyte ratio, neutrophil–monocyte ratio, monocyte–lymphocyte ratio, platelet–lymphocyte ratio, systemic immune‐inflammatory index [SII], systemic inflammatory response index [SIRI]), and lactate levels in differentiating SE from pPNES. Patients were identified from two tertiary hospitals, with one forming the development cohort and the other the validation cohort. Using generalized additive models to generate biomarker vs time curves, optimal blood collection times were defined for set parameters. Three diagnostic scores combining neutrophil count, SII, or SIRI with lactate levels were developed and validated in separate cohorts. Results: For the development cohort, 1262 seizure‐like events were reviewed and 79 SE and 44 pPNES events were included. For the validation cohort, 241 events were reviewed and 20 SE and 11 pPNES events were included. Individually, the biomarkers generally had low sensitivity and reasonable specificity for differentiating SE from pPNES, with the neutrophil count, SIRI, and SII performing best with sensitivities of 0.65–0.84, specificities of 0.64–0.89, and ROC AUCs of 0.78–0.79. Lactate levels peaked at 60 min, while cell counts and ratios peaked after 240 min. Combining early peaking lactate levels and later peaking neutrophil count, SIRI or SII resulted in three scores that improved predictive potential with sensitivities of between 0.75 and 0.79, specificities between 0.93 and 1.00, and ROC AUCs of 0.89–0.91. Significance: Lactate levels peak early post‐SE, whereas cell counts and ratios do so later. The differing post‐event time profiles of lactate levels vs neutrophil count, SIRI, and SII allow incorporation into three separate scores which can assist in differentiating SE from pPNES. [ABSTRACT FROM AUTHOR]

Background and purpose: Despite the rapid increase in research examining outcomes in autoimmune encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. The current study aimed to characterise psychometric outcomes in this population, and explore variables that may predict psychometric outcomes. Methods: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolitan hospitals in Victoria, Australia between January 2008 and July 2019. Frequency and pattern analysis were employed to define and characterize psychometric outcomes. Univariable logistic regression was performed to examine predictors of intact and pathological psychometric outcomes. Results: Deficits in psychometric markers of executive dysfunction were the most common finding in this cohort, followed by deficits on tasks sensitive to memory. A total of 54.2% of patients were classified as having psychometric impairments across at least two cognitive domains. Twenty‐nine patterns were observed, suggesting outcomes in AE are complex. None of the demographic data, clinical features or auxiliary examination variables were predictors of psychometric outcome. Conclusions: Cognitive outcomes in AE are complex. Further detailed and standardized cognitive testing, in combination with magnetic resonance imaging volumetrics and serum/cerebrospinal fluid biomarkers, is required to provide rigorous assessments of disease outcomes. [ABSTRACT FROM AUTHOR]

Neurocognitive compromise, neuropsychiatric symptoms and psychopathology are all evident in the acute stages of autoimmune encephalitides. These factors considerably affect functional independence after discharge. Drawing on psychometric assessments and qualitative descriptions, this review explores the nature, extent and diagnosis of cognitive disorder in autoimmune encephalitides. Potential pathophysiological and neuroanatomical architecture related to neurocognitive compromise in the acute and chronic stages of this illness is examined. In regard to outcomes, the review highlights clinicodemographic factors currently known to be associated with poorer cognitive outcome. Finally, the review delves into neuropsychiatric symptomology and psychological concerns that should be considered at diagnosis and during follow up of these patients. [ABSTRACT FROM AUTHOR]

Epilepsy is seen historically as a disease of aberrant neuronal signaling manifesting as seizures. With the discovery of numerous auto‐antibodies and the subsequent growth in understanding of autoimmune encephalitis, there has been an increasing emphasis on the contribution of the innate and adaptive immune system to ictogenesis and epileptogenesis. Pathogenic antibodies, complement activation, CD8+ cytotoxic T cells, and microglial activation are seen, to various degrees, in different seizure‐associated neuroinflammatory and autoimmune conditions. These aberrant immune responses are thought to cause disruptions in neuronal signaling, generation of acute symptomatic seizures, and, in some cases, the development of long‐term autoimmune epilepsy. Although early treatment with immunomodulatory therapies improves outcomes in autoimmune encephalitides and autoimmune epilepsies, patient identification and treatment selection are not always clear‐cut. This review examines the role of the different components of the immune system in various forms of seizure disorders including autoimmune encephalitis, autoimmune epilepsy, Rasmussen encephalitis, febrile infection–related epilepsy syndrome (FIRES), and new‐onset refractory status epilepticus (NORSE). In particular, the pathophysiology and unique cytokine profiles seen in these disorders and their links with diagnosis, prognosis, and treatment decision‐making are discussed. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disorder that increases the risk of morbidity and mortality. Autoimmune epilepsy is a subset of epilepsy that occurs in the setting of autoimmunity, such as in autoimmune encephalitis (AIE). AIE is an autoimmune disorder characterized by immune‐mediated neuroinflammation resulting in a variety of neurological symptoms, including psychiatric disturbance, cognitive dysfunction, and seizures. Seizures in AIE are thought to be a result of antibodies directed against neuronal cell‐surface proteins involved in synaptic transmission. The role of blood‐brain barrier dysfunction, myeloid cell infiltration, and the initiation of proinflammatory cascades in epileptogenesis has been shown to be important in animal models and human patients with epilepsy. Epileptogenesis in AIE is likely to arise from the synergistic effect of both innately driven neuroinflammation and antibody‐induced hyperexcitability. Together, these processes produce persistent drug‐resistant seizures that contribute to the morbidity seen in AIE. Understanding the proinflammatory pathways involved in this process may improve diagnostics and provide alternative treatment targets in AIE. [ABSTRACT FROM AUTHOR]

Mal de Meleda is a rare autosomal recessive genodermatosis caused by mutations in the ARS B ( SLURP1) gene, with possible founder effects in the Mediterranean and Adriatic regions. We report an affected individual from Indonesia without known consanguinity in the family, suggesting that SLURP1 gene mutations are ubiquitous. Recognition of the phenotype can be confirmed by genetic testing, thus facilitating genetic counselling. [ABSTRACT FROM AUTHOR]

Given a single-dose vaccine is protective for life, yellow fever vaccination could be offered before DMT commencement, especially if DMT initiation is delayed for other vaccinations. A small study of patients not on highly effective DMTs observed a significant increase in relapse rate following exposure to the yellow fever vaccine,11 although this was not corroborated in a recent case series.32 When yellow fever vaccination is essential, DMT cessation with a washout period is required. Keywords: Multiple sclerosis; Demyelinating diseases; Central nervous system infections; Vaccination EN Multiple sclerosis Demyelinating diseases Central nervous system infections Vaccination 350 350 1 05/04/21 20210501 NES 210501 In a new MS diagnosis, immunisation status may be overlooked - careful planning from early in the treatment course is key Multiple sclerosis (MS) is an autoimmune disorder treated with immunomodulatory or immunosuppressive disease-modifying therapies (DMTs). General vaccination considerations in patients with MS The immunisation status of patients should be considered at the time of MS diagnosis. [Extracted from the article]