Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Clinical Correlation of Altered Molecular Signatures in Epileptic Human Hippocampus and Amygdala.

Widespread alterations in the expression of various genes could contribute to the pathogenesis of epilepsy. The expression levels of various genes, including major inhibitory and excitatory receptors, ion channels, cell type-specific markers, and excitatory amino acid transporters, were assessed and compared between the human epileptic hippocampus and amygdala, and findings from autopsy controls. Moreover, the potential correlation between molecular alterations in epileptic brain tissues and the clinical characteristics of patients undergoing epilepsy surgery was evaluated. Our findings revealed significant and complex changes in the expression of several key regulatory genes in both the hippocampus and amygdala of patients with intractable epilepsy. The expression changes in various genes differed considerably between the epileptic hippocampus and amygdala. Different correlation patterns were observed between changes in gene expression and clinical characteristics, depending on whether the patients were considered as a whole or were subdivided. Altered molecular signatures in different groups of epileptic patients, defined within a given category, could be viewed as diagnostic biomarkers. Distinct patterns of molecular changes that distinguish these groups from each other appear to be associated with epilepsy-specific functional consequences.

Staged treatment response in status epilepticus: Lessons from the SENSE registry.

OBJECTIVES: Although in epilepsy patients the likelihood of becoming seizure-free decreases substantially with each unsuccessful treatment, to our knowledge this has been poorly investigated in status epilepticus (SE). We aimed to evaluate the proportion of SE cessation and functional outcome after successive treatment steps. METHODS: We conducted a post hoc analysis of a prospective, observational, multicenter cohort (Sustained Effort Network for treatment of Status Epilepticus [SENSE]), in which 1049 incident adult SE episodes were prospectively recorded at nine European centers. We analyzed 996 SE episodes without coma induction before the third treatment step. Rates of SE cessation, mortality (in ongoing SE or after SE control), and favorable functional outcome (assessed with modified Rankin scale) were evaluated after each step. RESULTS: SE was treated successfully in 838 patients (84.1%), 147 (14.8%) had a fatal outcome (36% of them died while still in SE), and 11 patients were transferred to palliative care while still in SE. Patients were treated with a median of three treatment steps (range 1-13), with 540 (54.2%) receiving more than two steps (refractory SE [RSE]) and 95 (9.5%) more than five steps. SE was controlled after the first two steps in 45%, with an additional 21% treated after the third, and 14% after the fourth step. Likelihood of SE cessation (p < 0.001), survival (p = 0.003), and reaching good functional outcome (p < 0.001) decreased significantly between the first two treatment lines and the third, especially in patients not experiencing generalized convulsive SE, but remained relatively stable afterwards. SIGNIFICANCE: The significant worsening of SE prognosis after the second step clinically supports the concept of RSE. However, and differing from findings in human epilepsy, RSE remains treatable in about one third of patients, even after several failed treatment steps. Clinical judgment remains essential to determine the aggressiveness and duration of SE treatment, and to avoid premature treatment cessation in patients with SE.

Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants in STXBP1.

BACKGROUND AND OBJECTIVES: Pathogenic variants in STXBP1 are among the major genetic causes of neurodevelopmental disorders. Despite the increasing number of individuals diagnosed without a history of epilepsy, little is known about the natural history and developmental trajectories in this subgroup and endpoints for future therapeutic studies are limited to seizure control. METHODS: We performed a cross-sectional retrospective study using standardized questionnaires for clinicians and caregivers of individuals with STXBP1-related disorders capturing medical histories, genetic findings, and developmental outcomes. Motor and language function were assessed using Gross Motor Function Classification System (GMFCS) scores and a speech impairment score and were compared within and across clinically defined subgroups. RESULTS: We collected data of 71 individuals with STXBP1-related disorders, including 44 previously unreported individuals. Median age at inclusion was 5.3 years (interquartile range 3.5-9.3) with the oldest individual aged 43.8 years. Epilepsy was absent in 18/71 (25%) of individuals. The range of developmental outcomes was broad, including 2 individuals presenting with close to age-appropriate motor development. Twenty-nine of 61 individuals (48%) were able to walk unassisted, and 24/69 (35%) were able to speak single words. Individuals without epilepsy presented with a similar onset and spectrum of phenotypic features but had lower GMFCS scores (median 3 vs 4, p < 0.01) than individuals with epilepsy. Individuals with epileptic spasms were less likely to walk unassisted than individuals with other seizure types (6% vs 58%, p < 0.01). Individuals with early epilepsy onset had higher speech impairment scores (p = 0.02) than individuals with later epilepsy onset. DISCUSSION: We expand the spectrum of STXBP1-related disorders and provide clinical features and developmental trajectories in individuals with and without a history of epilepsy. Individuals with epilepsy, in particular epileptic spasms, and neonatal or early-onset presented with less favorable motor and language functional outcomes compared with individuals without epilepsy. These findings identify children at risk for severe disease and can serve as comparator for future interventional studies in STXBP1-related disorders.

Concurrent recordings of slow DC-potentials and epileptiform discharges: Novel EEG amplifier and signal processing techniques.

Ionic currents within the brain generate voltage oscillations. These bioelectrical activities include ultra-low frequency electroencephalograms (DC-EEG, frequency less than 0.1 Hz) and conventional clinical electroencephalograms (AC-EEG, 0.5-70 Hz). Although AC-EEG is commonly used for diagnosing epilepsy, recent studies indicate that DC-EEG is an essential frequency component of EEG and can provide valuable information for analyzing epileptiform discharges. During conventional EEG recordings, DC-EEG is censored by applying high-pass filtering to i) obliterate slow-wave artifacts, ii) eliminate the bioelectrodes' half-cell potential asymmetrical changes in ultralow-low frequency, and iii) prevent instrument saturation. Spreading depression (SD), which is the most prolonged fluctuation in DC-EEG, may be associated with epileptiform discharges. However, recording of SD signals from the scalp's surface can be challenging due to the filtering effect and non-neuronal slow shift potentials. In this study, we describe a novel technique to extend the frequency bandwidth of surface EEG to record SD signals. The method includes novel instrumentation, appropriate bioelectrodes, and efficient signal-processing techniques. To evaluate the accuracy of our approach, we performed a simultaneous surface recording of DC- and AC-EEG from epileptic patients during long-term video EEG monitoring, which provide a promising tool for diagnosis of epilepsy. DATA AVAILABILITY STATEMENT: The data presented in this study are available on request.

Making SENSE of what we do - How to bring evidence to clinical practice.

Status epilepticus is a frequent neurological emergency. Several audits and registries have enhanced our knowledge regarding patient demography, etiology, treatment, and outcome. Several large registries have also contributed significantly to current treatment guidelines that emphasize the importance of instant and effective treatment onset. Large registries also document that deviation from these treatment guidelines is not the exception but the rule. Therefore, careful analysis of the treatment pathways as well as balanced intervention efforts are necessary to overcome the gap between knowledge and action. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

A genome-wide association study in autoimmune neurological syndromes with anti-GAD65 autoantibodies.

Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P < 5 × 10-8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10-16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187-0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci (>90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10-4, OR = 2.5, 95%CI = 1.499-4.157) and DRB1*04:01 allele (P = 8.3 × 10-5, OR = 2.4, 95%CI = 1.548-3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles.

Teaching distinguishing semiological features improves diagnostic accuracy of seizure-like events by emergency physicians.

BACKGROUND: Misdiagnosis of seizure-like events (SLE) in emergency situations is common. Here, we evaluate whether a single, video-based lesson highlighting distinguishing semiological features can improve the diagnostic accuracy of emergency physicians for epileptic seizures (ES), psychogenic non-epileptic seizures (PNES) and syncopes (SY). METHODS: 40 emergency physicians (24 anesthetists, nine surgeons and seven internal medicine specialists by primary specialty) participated in a prospective trial on the diagnostic accuracy of SLE. They assessed video-displayed SLE at two time points: before and after a lecture on distinguishing semiological features. In the lecture, semiological features were demonstrated using patient videos, some were acted by the instructor in addition. The increase in correct diagnoses and recognition of distinguishing semiological features were analyzed. RESULTS: Before the lesson, 45% of 200 SLE-ratings were correct: 15% of SY (n = 40), 30% of PNES (n = 40), 59% of ES (n = 120, focal to bilateral tonic-clonic seizures (FBTCS) 87.5% (n = 40), focal impaired aware seizures (FIAS) 45% (n = 80)). Semiology teaching increased both the rate of correct diagnoses of SLE to overall 79% (p < 0.001) (ES 91% (p < 0.001), FBCTS 98% (n.s.), FIAS 88% (p < 0.001), PNES 88% (p < 0.001), SY 35% (p < 0.001)), and the number of recognized distinguishing semiological features. We identified several semiological features with high entity specific positive predictive values (> 0.8). CONCLUSIONS: A single 45-min video-based lesson highlighting distinguishing semiological features improves the diagnostic accuracy of ES, PNES and SY by emergency physicians. We expect that including this aspect into the curriculum of emergency physicians will lead to better individual patient treatment in pre-hospital medicine and more appropriate subsequent use of clinical resources.

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD). METHODS: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis. RESULTS: Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with déjà-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients. DISCUSSION: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.

Successful treatment of adult Dravet syndrome patients with cenobamate.

Dravet syndrome (DS) is a rare, drug-resistant, severe developmental and epileptic encephalopathy caused by pathogenic variants in the α subunit of the voltage-gated sodium channel gene SCN1A. Hyperexcitability in DS results from loss of function in inhibitory interneurons. Thus sodium channel blockers are usually contraindicated in patients with DS as they may lead to disease aggravation. Cenobamate (CNB) is a novel antiseizure medication (ASM) with promising rates of seizure freedom in patients with focal-onset, drug-resistant epilepsy. CNB blocks persistent sodium currents by promoting the inactive states of sodium channels. In a multi-center study, we analyzed retrospectively the effect of an add-on therapy of CNB in adult patients with DS. We report four adult patients with DS in whom the use of CNB resulted in a significant seizure reduction of more than 80%, with a follow-up of up to 542 days. CNB was the first drug in these patients that resulted in a long-lasting and significant seizure reduction. No severe adverse events occurred. We highlight CNB as an ASM that may lead to a clinically meaningful reduction of seizure frequency in adult patients with DS. It is unclear, however, if all patients with DS benefit, requiring further investigation and functional experiments.

Refractory Status Epilepticus: Risk Factors and Analysis of Intubation in the Multicenter SENSE Registry.

BACKGROUND AND OBJECTIVES: Refractory status epilepticus (RSE) bears significant morbidity and mortality. Therapy escalation and in some cases intubation are recommended. Most existing studies are retrospective and focus on intensive care units. We aimed to describe routine-care management and analyze determinants of RSE development and outcomes in a large multicenter cohort. METHODS: We performed post hoc analysis of an observational, cohort study, which prospectively registered all consecutive adults with SE at 9 centers from 3 central European countries. Only incident episodes were included. Ongoing SE despite 2 antiseizure medications was defined as RSE. Patients intubated during first-line or second-line treatments were excluded. Variables investigated included demographics, severity (Status Epilepticus Severity Score), etiology, and guideline-compliant treatment (defined as fixed minimum doses). Outcome parameters included survival and mRS at baseline, and discharge (good: 0-2, or absence of worsening compared with prehospitalization). RESULTS: Among 1,179 SE episodes from 1,049 adults, 996 patients were eligible (median age: 70 years, 52% female), of which 545 (54.7%) developed RSE. RSE was associated with higher baseline mRS (p < 0.001) and treatment deviation from guidelines (p < 0.001, OR 0.09; 95% CI 0.06-0.1). Good outcomes were observed in 52.7% of refractory patients, correlating with lower status epilepticus severity (p < 0.001), absence of acute etiology (p < 0.001, OR 0.5; 95% CI 0.3-0.7), adequate first-line benzodiazepine dose (p < 0.001, OR 2.5; 95% CI 1.6-4.0), shorter durations of SE and hospitalization (both p < 0.001), and lack of intubation (p < 0.001, OR 0.4; 95% CI 0.3-0.6). Most (71.7%) refractory patients were not intubated. Intubation was associated with younger age (p = 0.006), more severe consciousness disturbances (p < 0.001, OR 3.2; 95% CI 2.1-4.8), more severe SE types (p < 0.001), higher severity score (p = 0.009), acute etiologies (p = 0.01, OR 1.6; 95% CI 1.1-2.4), more antiseizure medications (p < 0.001), initial treatment after shorter latency (p = 0.01), worse outcomes (p < 0.001, OR 0.4; 95% CI 0.4-0.6), and longer hospitalizations (p < 0.001). DISCUSSION: Variables associated with RSE were identified, some potentially preventable. More than 70% of RSE were treated without intubation, suggesting that focal RSE without deep impairment of consciousness, in older patients, may be successfully treated outside ICUs. TRIAL REGISTRATION INFORMATION: Original cohort study registered at the German Clinical Trials Register (DRKS00000725).

New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) of unknown aetiology: A comparison of the incomparable?

PURPOSE: The discussion is ongoing whether new-onset refractory status epilepticus (NORSE) in adults and febrile infection-related epilepsy syndrome (FIRES) in children are one syndrome if the aetiology is unknown. In this study we will compare an adult cohort with NORSE and a paediatric cohort with FIRES in order to determine if they are similar or different. METHODS: We retrospectively compared 18 adults with NORSE versus 48 children with FIRES, both cohorts without identifiable cause despite extensive investigations. We analyzed demographic and clinical data using Mann-Whitney-U and χ2- tests. RESULTS: NORSE affected more women (78% vs. 42%; P = 0.009) than in FIRES. Median acute hospital stay was longer in FIRES (35 days [interquartile range, IQR=36] vs. 20 days [IQR=19]; P<0.001). FIRES was treated more frequently with coma therapy (82% vs. 28%; P<0.001) and with a higher median number of antiseizure medicines (7 [IQR=5] vs. 4 [IQR=2]; P<0.001). Children with FIRES showed a higher cerebrospinal fluid (CSF) cell count (10 cells/µl; P = 0.002) but a lower CSF protein level than adults with NORSE (48 mg/dl; P = 0.028). Immunotherapy was administered more frequently in FIRES (73% vs. 22%; P<0.001) than in NORSE. Group differences in number of antiseizure medicines after hospital stay (P = 0.229) and in overall mortality (P = 0.327) were not significant. CONCLUSION: In our explorative comparison, differences prevailed. NORSE and FIRES should be compared prospectively in age-matched cohorts.

CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: CSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated protein 1 antibodies (LGI1-E) represent opposite ends of this spectrum: NMDAR-E with typically frequent/robust and LGI1-E with rare/mild CSF inflammation. For a more in-depth analysis, we characterized CSF findings in acute, therapy-naive NMDAR-E and LGI1-E in a multicentric, retrospective, cross-sectional setting. METHODS: Eighty-two patients with NMDAR-E and 36 patients with LGI1-E from the GErman NEtwork for Research of AuToimmune Encephalitis (GENERATE) with lumbar puncture within 90 days of onset and before immunotherapy were included. CSF parameters comprised leukocytes, oligoclonal bands (OCBs), and CSF/serum ratios for albumin, immunoglobulin G (IgG), A (IgA), and M (IgM), the latter 3 converted to Z scores according to Reiber formulas. The MRZ reaction was tested in 14 patients with NMDAR-E and 6 patients with LGI1-E, respectively. RESULTS: CSF was abnormal in 94% of NMDAR-E but only in 36% of LGI1-E patients. Robust quantitative intrathecal immunoglobulin synthesis (IIS, IgG > IgM >> IgA) was characteristic for NMDAR-E, but absent in LGI-E. In NMDAR-E, CSF leukocytes were higher when IIS was present or more pronounced. In addition, in NMDAR-E, CSF leukocytes were lower and IIS occurred less often and if so to a lesser degree at older age. Patients with NMDAR-E with severe functional impairment more often had positive OCBs. In CSF obtained later than 3 weeks of onset, leukocytes were lower. In parallel, the correlation of leukocytes with IIS disappeared as IIS was partially independent of disease duration. The MRZ reaction was positive in 5 (36%) patients with NMDAR-E. All these associations were completely absent in LGI1-E. Here, younger patients showed more blood-CSF barrier dysfunction. In LGI1-E, but not in NMDAR-E, the blood-CSF barrier was more dysfunctional when CSF leukocytes were higher. DISCUSSION: NMDAR-E and LGI-E differ in their typical extent of CSF inflammation. In addition, the patterns formed by the different inflammatory CSF parameters and their relationship with disease severity, age, and disease duration are subtype-characteristic. Moreover, signs for multiple sclerosis-like chronic inflammation are present in a subgroup of patients with NMDAR-E. These CSF patterns might be markers for the different immunopathogeneses of LGI1-E and NMDAR-E.

Satisfaction with and reliability of in-hospital video-EEG monitoring systems in epilepsy diagnosis - A German multicenter experience.

OBJECTIVE: To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics. METHODS: A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics. RESULTS: Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service. CONCLUSION: Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management. SIGNIFICANCE: This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement.

Occurrence of status epilepticus in persons with epilepsy is determined by sex, epilepsy classification, and etiology: a single center cohort study.

BACKGROUND: Status epilepticus (SE) can occur in persons with or without epilepsy and is associated with high morbidity and mortality. METHODS: This survey aimed to record self-reported frequency of SE in persons with epilepsy, its association with clinical characteristics and patient level of information on SE and rescue medication. 251 persons with epilepsy at a tertiary epilepsy center were included in the study. RESULTS: 87 (35%) had a history of SE defined as seizure duration of more than 5 min. These patients were less likely to be seizure-free, and had a higher number of present and past anti-seizure medication. Female sex, cognitive disability, younger age at epilepsy onset, defined epilepsy etiology, and focal epilepsy were associated with a history of SE. On Cox regression analysis, female sex, defined etiology and focal classification remained significant. 67% stated that they had information about prolonged seizures, and 75% knew about rescue medication. 85% found it desirable to receive information about SE at the time of initial diagnosis of epilepsy, but only 16% had been offered such information at the time. CONCLUSION: SE is frequent among persons with epilepsy and there remain unmet needs regarding patient education.

Association of cortical spreading depression and seizures in patients with medically intractable epilepsy.

OBJECTIVE: Monitoring of the ultra-low frequency potentials, particularly cortical spreading depression (CSD), is excluded in epilepsy monitoring due to technical barriers imposed by the scalp ultra-low frequency electroencephalogram (EEG). As a result, clinical studies of CSD have been limited to invasive EEG. Therefore, the occurrence of CSD and its interaction with epileptiform field potentials (EFP) require investigation in epilepsy monitoring. METHODS: Using a novel AC/DC-EEG approach, the occurrence of DC potentials in patients with intractable epilepsy presenting different symptoms of aura was investigated during long-term video-EEG monitoring. RESULTS: Various forms of slow potentials, including simultaneous negative direct current (DC) potentials and prolonged EFP, propagated negative DC potentials, and non-propagated single negative DC potentials were recorded from the scalp of the epileptic patients. The propagated and single negative DC potentials preceded the prolonged EFP with a time lag and seizure appeared at the final shoulder of some instances of the propagated negative DC potentials. The slow potential deflections had a high amplitude and prolonged duration and propagated slowly through the brain. The high-frequency EEG was suppressed in the vicinity of the negative DC potential propagations. CONCLUSIONS: The study is the first to report the recording of the propagated and single negative DC potentials with EFP at the scalp of patients with intractable epilepsy. The negative DC potentials preceded the prolonged EFP and may trigger seizures. The propagated and single negative DC potentials may be considered as CSD. SIGNIFICANCE: Recordings of CSD may serve as diagnostic and prognostic monitoring tools in epilepsy.

Sustained Effort Network for treatment of Status Epilepticus (SENSE) - A multicenter prospective observational registry.

Status epilepticus (SE) is an important neurological emergency lacking adequate evidence for efficacy and safety of treatment beyond the application of benzodiazepines as first treatment step. To bridge the gap between the few pivotal trials and retrospective uncontrolled case series, we established a prospective multicenter registry recruiting patients in experienced centers in German-speaking countries. We could document 1179 episodes of 1049 patients over a period of 5 years. First data analysis showed that in the majority of the episodes, established treatment guidelines were not followed. Latency between status onset and different treatment steps were longer, and bolus doses lower than recommended. Moreover, a relevant proportion of the patients did not receive a benzodiazepine but levetiracetam as first treatment step. Although SE could be controlled in more than 90% of the episodes, lower bolus dose and longer treatment latency were associated with refractoriness of the SE in multivariate analysis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

OBJECTIVE: To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. METHODS: Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. RESULTS: Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. INTERPRETATION: In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.