Explore the vast range of titles available.

Determination of prognosis in patients with status epilepticus (SE)—a life-threatening state of ongoing or repetitive seizures—is difficult, and current outcome prediction scales do not take into account novel outcome markers, such as EEG and imaging findings. Here, Sutter et al . review the available data on major prognostic determinants of outcome in SE, and propose a novel paradigm for assessment of these predictive factors over the course of the seizure. In adult patients with status epilepticus (SE)—a life-threatening state of ongoing or repetitive seizures—the current evidence regarding outcome prediction is based on clinical, biochemical and EEG determinants. These predictors of outcome involve clinical features such as age, history of prior seizures or epilepsy, SE aetiology, level of consciousness, and seizure type at SE onset. The clinical risk–benefit calculation between the danger of undertreated persistent seizure activity and, conversely, the potential damage from unwarranted aggressive treatments remains a constant challenge. Improved knowledge of outcome determinants, as well as increased availability of reliable outcome prediction models early in the course of SE, is paramount for optimization of treatment of patients who develop this disorder. In this Review, we discuss the major prognostic determinants of outcome in SE. Through consideration of studies that provide measures of association between predictors of SE outcome and death, we propose a detailed—but as yet unvalidated—paradigm for assessment of these predictors during the course of SE. Such an algorithm could guide the organization of results from existing trials and provide direction with regard to the parameters that should be monitored in future studies of SE. Key Points The most reliable clinical determinants for early prediction of outcome in status epilepticus (SE) are age, prior seizures or epilepsy, SE aetiology, level of consciousness, and seizure type at onset These variables have been integrated and validated in a clinical scoring system (the Status Epilepticus Outcome Score) for rapid outcome prognostication at SE onset The current outcome score for SE does not encompass the totality of aetiological, biochemical and EEG characteristics—factors that interact in a complex manner and show promise for outcome prognostication On the basis of the available data, we propose a detailed—but as yet unvalidated—paradigm for the assessment of outcome predictors during the course of SE

Background Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. Methods In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. Results Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p  = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p  = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p  = 0.002). With longer SE duration (1 day vs. 0.5 days, p  = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p  = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p  = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p  < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p  = 0.004). Conclusions This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Background Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial cytopathy caused by mutations in mitochondrial DNA. Clinical manifestation is typically before the age of 40. Case presentation We present the case of a 63-year-old female in whom the symptoms of MELAS were initially misdiagnosed as episodes of recurrent ischemic strokes. Brain imaging including MRI, clinical and laboratory findings that lent cues to the diagnosis of MELAS are discussed. In addition, MRI findings in MELAS in comparison to imaging mimics of MELAS are presented. Conclusions This case underscores the importance of considering MELAS as a potential cause of recurrent stroke-like events if imaging findings are untypical for cerebral infarction, even among middle-aged patients with vascular risk factors.

Repeated MRIs, from days 5 to 12 after admission, showed progression of the multiple cortico-subcortical lesions ( figure); the EEG showed right-hemispheric temporo-parietal focal slowing independent of the worsening of the patient's condition. UFischer reports research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, Medtronic, Stryker, Penumbra, Rapid medical, Phenox, and Boehringer Ingelheim; consulting fees from Medtronic, Stryker, CSL Behring (fees paid to institution); has membership in a data safety monitoring board for the TITAN trial, IN EXTREMIS trial, LATE-MT trial, Rapid Puls Trial; has membership in the Clinical Event Committee of the COATING Trial (Phenox) and membership in the advisory board for CLS Behring, Acthera, Alexion/Portola, Boehringer Ingelheim (all fees paid to institution); is president of the Swiss Neurological Society. Acknowledgments We thank the patient for his consent and all health-care professionals who were involved in his treatment at the Department of Neurology; Department of Radiology; Department of Intensive Care; Department of Medicine; Department of Anaesthesiology; Institute of Pathology; Department of Neurosurgery; and the Emergency Department of the University Hospital Basel, Switzerland; the REHAB Clinic for Neurorehabilitation, Basel, Switzerland; and the Laboratory Krone, Bad Salzuflen, Germany.

Background Early prognostication in patients with acute consciousness impairment is a challenging but essential task. Current prognostic guidelines vary with the underlying etiology. In particular, electroencephalography (EEG) is the most important paraclinical examination tool in patients with hypoxic ischemic encephalopathy (HIE), whereas it is not routinely used for outcome prediction in patients with traumatic brain injury (TBI). Method Data from 364 critically ill patients with acute consciousness impairment (GCS ≤ 11 or FOUR ≤ 12) of various etiologies and without recent signs of seizures from a prospective randomized trial were retrospectively analyzed. Random forest classifiers were trained using 8 visual EEG features—first alone, then in combination with clinical features—to predict survival at 6 months or favorable functional outcome (defined as cerebral performance category 1–2). Results The area under the ROC curve was 0.812 for predicting survival and 0.790 for predicting favorable outcome using EEG features. Adding clinical features did not improve the overall performance of the classifier (for survival: AUC = 0.806, p  = 0.926; for favorable outcome: AUC = 0.777, p  = 0.844). Survival could be predicted in all etiology groups: the AUC was 0.958 for patients with HIE, 0.955 for patients with TBI and other neurosurgical diagnoses, 0.697 for patients with metabolic, inflammatory or infectious causes for consciousness impairment and 0.695 for patients with stroke. Training the classifier separately on subgroups of patients with a given etiology (and thus using less training data) leads to poorer classification performance. Conclusions While prognostication was best for patients with HIE and TBI, our study demonstrates that similar EEG criteria can be used in patients with various causes of consciousness impairment, and that the size of the training set is more important than homogeneity of ACI etiology.

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.

Objective The 2014 update of the Swiss law on research increases patients' protection; it adds specific requirements for emergency situations, implying an active search for patients' wishes regarding research participation; the possibility of consent waivers is not clearly stated. We explored its practical impact in a RCT on critically ill adults. Methods We considered prospectively collected consents of a multicenter trial addressing the impact of continuous EEG on survival. We assessed the proportions of consents obtained strictly according to the law, of specific waivers for this study obtained from the IRB (early death; relatives' unavailability despite repeated attempts), and the yield of retrieving statements on willingness to research participation. We compared the proportion of consent refusals with those of recent trials in similar environments, and estimated the potential impact on study results. Results Of 402 recruited patients, six had double inclusions, one died before intervention, and 27 (6.7%, alive on long‐term) were excluded following consent refusal or withdrawal, leaving 368 analyzable patients. Specific waivers allowed inclusion of 134 (36.4%) patients, while informed consents were obtained for all others. A statement of willingness to research participation was found in only 14.1%. In recent trials, consent refusal oscillated between 0%–23%, according to different waiver policies. Conclusions Consent waivers should be specifically foreseen to prevent losing a potentially relevant proportion of patients reaching endpoints, and ensure results generalizability. The yield of looking for willingness to research participation seems low; this questions its current usefulness and calls for a public awareness campaign. This study analyzes the informed consent flow in a multicenter RCT carried out in critically ill adults and shows that data from 7% of recruited subjects had to be discarded due to lack of consent; this modified the primary endpoint (mortality). Furthermore, 36% of recruited subjects could be analyzed only following a specific waiver accorded from the Ethics Commission. These results highlight critical issues regarding generalizability of results, namely the importance of providing specific waivers in this clinical context and to address drop‐out rates due to lack of consents.

Seizures and epilepsy can result from various aetiologies, yet the underlying cause of several epileptic syndromes remains unclear. In that regard, autoimmune-mediated pathophysiological mechanisms have been gaining attention in the past years and were included as one of the six aetiologies of seizures in the most recent classification of the International League Against Epilepsy. The increasing number of anti-neuronal antibodies identified in patients with encephalitic disorders has contributed to the establishment of an immune-mediated pathophysiology in many cases of unclear aetiology of epileptic syndromes. Yet only a small number of patients with autoimmune encephalitis develop epilepsy in the proper sense where the brain transforms into a state where it will acquire the enduring propensity to produce seizures if it is not hindered by interventions. Hence, the term autoimmune epilepsy is often wrongfully used in the context of autoimmune encephalitis since most of the seizures are acute encephalitis-associated and will abate as soon as the encephalitis is in remission. Given the overlapping clinical presentation of immune-mediated seizures originating from different aetiologies, a clear distinction among the aetiological entities is crucial when it comes to discussing pathophysiological mechanisms, therapeutic options, and long-term prognosis of patients. Moreover, a rapid and accurate identification of patients with immune-mediated epilepsy syndromes is required to ensure an early targeted treatment and, thereby, improve clinical outcome. In this article, we review our current understanding of pathogenesis and critically discuss current and potential novel treatment options for seizures and epilepsy syndromes of underlying or suspected immune-mediated origin. We further outline the challenges in proper terminology.

With advances in critical care and organ donation, diagnosis of brain death is gaining importance. We aimed to assess potential brain death confounders from the literature, elucidating clinical presentation and diagnostic approaches in these cases. PubMed and Embase were screened using 37 predefined search terms to identify suitable articles reporting cases, case series, or cohort studies in adults. Out of 4769 articles, 40 case reports or case series describing 45 patients with 19 critical conditions were identified. Mortality was 11% and full recovery 33%. Intoxications (42%; mainly anti-seizure drugs and baclofen) and polyneuritis (37%) were most frequent. Brainstem reflex tests were reported in 96%, apnoea test in 16% and ancillary tests in all but one patient. Full recovery mainly occurred with intoxications. Quality of evidence regarding frequency of confounders is very low and risk of bias high. Brain death confounders are infrequently reported and formal studies are lacking. Mainly younger patients with polyneuritis and intoxications are described. As outcome, especially in the latter, is often favourable, high awareness and strict adherence to guidelines is crucial. The importance of identifying pathologies compatible with extensive and irreversible brain damage before proceeding to diagnostic tests should be emphasized. •Brain death confounders are infrequently reported and formal studies are lacking, so the level of evidence is low.•Mainly younger patients with polyneuritis and intoxications are described.•Strict adherence to guidelines is crucial to prevent potentially harmful procedures, and unjustifiable care withdrawal.