A Comprehensive Review and Practical Guide of the Applications of Evoked Potentials in Neuroprognostication After Cardiac Arrest.

Cardiorespiratory arrest is a very common cause of morbidity and mortality nowadays, and many therapeutic strategies, such as induced coma or targeted temperature management, are used to reduce patient sequelae. However, these procedures can alter a patient's neurological status, making it difficult to obtain useful clinical information for the reliable estimation of neurological prognosis. Therefore, complementary investigations are conducted in the early stages after a cardiac arrest to clarify functional prognosis in comatose cardiac arrest survivors in the first few hours or days. Current practice relies on a multimodal approach, which shows its greatest potential in predicting poor functional prognosis, whereas the data and tools to identify patients with good functional prognosis remain relatively limited in comparison. Therefore, there is considerable interest in investigating alternative biological parameters and advanced imaging technique studies. Among these, somatosensory evoked potentials (SSEPs) remain one of the simplest and most reliable tools. In this article, we discuss the technical principles, advantages, limitations, and prognostic implications of SSEPs in detail. We will also review other types of evoked potentials that can provide useful information but are less commonly used in clinical practice (e.g., visual evoked potentials; short-, medium-, and long-latency auditory evoked potentials; and event-related evoked potentials, such as mismatch negativity or P300).

Stroke Recovery-Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition.

BACKGROUND: Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke. METHODS: Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation. RESULTS: From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (Pcluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics. CONCLUSIONS: The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.

Ceftriaxone-induced encephalopathy in a patient with a normal renal function.

Ceftriaxone-induced encephalopathy is an exceptionally rare adverse effect of this commonly used cephalosporin and is generally observed in patients undergoing haemodialysis or suffering from severe renal failure. We present a case of a fit woman in her mid-80s with a normal renal function who developed severe fluctuating neurological symptoms (aphasia, loss of contact, chorea-like tongue movements) while being treated with ceftriaxone for a urinary tract infection with bacteraemia. The symptoms began on day 4 of treatment and an adverse drug reaction was suspected on day 7, after exhaustive investigations failed to reveal another cause. A complete recovery was observed 3 days after discontinuing ceftriaxone. Our case highlights the need to consider the diagnosis of ceftriaxone encephalopathy, even if the traditional risk factors are lacking. In this article, we also provide a brief overview of the pathophysiology as well as a literature review concerning the subject.

Isolated invasive fungal sphenoid sinusitis-induced extensive bone erosion and severe meningoencephalitis: diagnosis and multidisciplinary management.

Invasive fungal sinusitis (IFS) is more common in immunosuppressed patients but can also occur in immunocompetent hosts. While the non-invasive type of fungal sinusitis has usually a good prognosis, IFS is a potentially lethal condition.We report the case of a woman in her 60s presenting an isolated fungal infection by Aspergillus fumigatus of the right sphenoid sinus, causing extensive bone erosion of its walls and complicated by severe meningoencephalitis. She was healthy without any immunosuppressive conditions. Methods of diagnosis, multidisciplinary management, follow-up and outcomes are documented.Early-stage diagnosis of sphenoid sinus pathologies is often delayed because patients are usually asymptomatic. IFS of the sphenoid is more aggressive than other paranasal sinus and carries significant mortality. Early diagnosis and aggressive and multidisciplinary treatment are crucial to reduce sequels and improve patient's survival.

Differential Impact of Brain Network Efficiency on Poststroke Motor and Attentional Deficits.

BACKGROUND: Most studies on stroke have been designed to examine one deficit in isolation; yet, survivors often have multiple deficits in different domains. While the mechanisms underlying multiple-domain deficits remain poorly understood, network-theoretical methods may open new avenues of understanding. METHODS: Fifty subacute stroke patients (7±3days poststroke) underwent diffusion-weighted magnetic resonance imaging and a battery of clinical tests of motor and cognitive functions. We defined indices of impairment in strength, dexterity, and attention. We also computed imaging-based probabilistic tractography and whole-brain connectomes. To efficiently integrate inputs from different sources, brain networks rely on a rich-club of a few hub nodes. Lesions harm efficiency, particularly when they target the rich-club. Overlaying individual lesion masks onto the tractograms enabled us to split the connectomes into their affected and unaffected parts and associate them to impairment. RESULTS: We computed efficiency of the unaffected connectome and found it was more strongly correlated to impairment in strength, dexterity, and attention than efficiency of the total connectome. The magnitude of the correlation between efficiency and impairment followed the order attention>dexterity ≈ strength (strength: |r|=.03, P=0.02, dexterity: |r|=.30, P=0.05, attention: |r|=.55, P<0.001). Network weights associated with the rich-club were more strongly correlated to efficiency than non-rich-club weights. CONCLUSIONS: Attentional impairment is more sensitive to disruption of coordinated networks between brain regions than motor impairment, which is sensitive to disruption of localized networks. Providing more accurate reflections of actually functioning parts of the network enables the incorporation of information about the impact of brain lesions on connectomics contributing to a better understanding of underlying stroke mechanisms.

Toward individualized medicine in stroke-The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke.

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.

Management Strategy of Intracranial Complications of Sinusitis: Our Experience and Review of the Literature.

Objective: Sinusitis or rhinosinusitis is a very common disease worldwide, and in some cases, it leads to intracranial complications (ICS). These are more common in immunocompromised patients or with underlying comorbidities, but even healthy individuals, can be affected. Nowadays, ICS have become less common thanks to improved antibiotic therapies, radiological diagnostic methods, surgical techniques and skills. Nonetheless, they can still cause significant morbidity and mortality. For this reason, management of these complications requires a multidisciplinary approach to plan and customize treatment options. This paper presents our strategy in the management of a series of intracranial complications induced by acute sinusitis and compares our experience and outcomes with the literature. Study design: Single institute experience, retrospective analysis of cases series and literature review. Methods: Adult and child patients who were treated for ICS in the Department of Otorhinolaryngology at Sion Hospital, in Switzerland from 2016 to 2020 were included. Their symptoms, medical history, clinical and radiological findings, treatment, and outcome were documented. Results: Eight patients (6 males- 2 females) aged from 14 to 88 y.o., were enrolled. None had any previous history of chronic, or recurrent sinusitis. Moreover, very few presented specific rhinological symptoms, but with neurological or other symptoms. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) were used to confirm the diagnosis of all ICS. All types of known intracranial complications were observed in our cohort with a wide range of extension and severity of sinusitis. A multidisciplinary approach with individual treatments was tailored to each patient. Outcomes were favorable in almost all patients with neither recurrence, nor neurological sequels being observed in the follow-up. Only one patient was lost due to fatal complications of advanced lung cancer. Conclusion: ICS remain a challenging clinical problem due to substantial associated morbidity and mortality. The incidence of these complications is relatively low. Therapeutical management guidelines are lacking. Early detection and multidisciplinary approach are key to successful treatment.

Diagnostic and prognostic EEG analysis of critically ill patients: A deep learning study.

Visual interpretation of electroencephalography (EEG) is time consuming, may lack objectivity, and is restricted to features detectable by a human. Computer-based approaches, especially deep learning, could potentially overcome these limitations. However, most deep learning studies focus on a specific question or a single pathology. Here we explore the potential of deep learning for EEG-based diagnostic and prognostic assessment of patients with acute consciousness impairment (ACI) of various etiologies. EEGs from 358 adults from a randomized controlled trial (CERTA, NCT03129438) were retrospectively analyzed. A convolutional neural network was used to predict the clinical outcome (based either on survival or on best cerebral performance category) and to determine the etiology (four diagnostic categories). The largest probability output served as marker for the confidence of the network in its prediction ("certainty factor"); we also systematically compared the predictions with raw EEG data, and used a visualization algorithm (Grad-CAM) to highlight discriminative patterns. When all patients were considered, the area under the receiver operating characteristic curve (AUC) was 0.721 for predicting survival and 0.703 for predicting the outcome based on best CPC; for patients with certainty factor ≥ 60 % the AUCs increased to 0.776 and 0.755 respectively; and for certainty factor ≥ 75 % to 0.852 and 0.879. The accuracy for predicting the etiology was 54.5 %; the accuracy increased to 67.7 %, 70.3 % and 84.1 % for patients with certainty factor of 50 %, 60 % and 75 % respectively. Visual analysis showed that the network learnt EEG patterns typically recognized by human experts, and suggested new criteria. This work demonstrates for the first time the potential of deep learning-based EEG analysis in critically ill patients with various etiologies of ACI. Certainty factor and post-hoc correlation of input data with prediction help to better characterize the method and pave the route for future implementations in clinical routine.

Continuous versus routine EEG in patients after cardiac arrest: Analysis of a randomized controlled trial (CERTA).

BACKGROUND: Electroencephalography (EEG) is essential to assess prognosis in patients after cardiac arrest (CA). Use of continuous EEG (cEEG) is increasing in critically-ill patients, but it is more resource-consuming than routine EEG (rEEG). Observational studies did not show a major impact of cEEG versus rEEG on outcome, but randomized studies are lacking. METHODS: We analyzed data of the CERTA trial (NCT03129438), including comatose adults after CA undergoing cEEG (30-48 hours) or two rEEG (20-30 minutes each). We explored correlations between recording EEG type and mortality (primary outcome), or Cerebral Performance Categories (CPC, secondary outcome), assessed blindly at 6 months, using uni- and multivariable analyses (adjusting for other prognostic variables showing some imbalance across groups). RESULTS: We analyzed 112 adults (52 underwent rEEG, 60 cEEG,); 31 (27.7%) were women; 68 (60.7%) patients died. In univariate analysis, mortality (rEEG 59%, cEEG 65%, p = 0.318) and good outcome (CPC 1-2; rEEG 33%, cEEG 27%, p = 0.247) were comparable across EEG groups. This did not change after multiple logistic regressions, adjusting for shockable rhythm, time to return of spontaneous circulation, serum neuron-specific enolase, EEG background reactivity, regarding mortality (cEEG vs rEEG: OR 1.60, 95% CI 0.43-5.83, p = 0.477), and good outcome (OR 0.51, 95% CI 0.14-1.90, p = 0.318). CONCLUSION: This analysis suggests that cEEG or repeated rEEG are related to comparable outcomes of comatose patients after CA. Pending a prospective, large randomized trial, this finding does not support the routine use of cEEG for prognostication in this setting. TRIAL REGISTRATION: Continuous EEG Randomized Trial in Adults (CERTA); NCT03129438; July 25, 2019.

EEG recording latency in critically ill patients: Impact on outcome. An analysis of a randomized controlled trial (CERTA).

OBJECTIVE: To assess, in adults with acute consciousness impairment, the impact of latency between hospital admission and EEG recording start, and their outcome. METHODS: We reviewed data of the CERTA trial (NCT03129438) and explored correlations between EEG recording latency and mortality, Cerebral Performance Categories (CPC), and modified Rankin Scale (mRS) at 6 months, considering other variables, using uni- and multivariable analyses. RESULTS: In univariable analysis of 364 adults, median latency between admission and EEG recordings was comparable between surviving (61.1 h; IQR: 24.3-137.7) and deceased patients (57.5 h; IQR: 22.3-141.1); p = 0.727. This did not change after adjusting for potential confounders, such as lower Glasgow Coma Score on enrolment (p < 0.001) and seizure or status epilepticus detection (p < 0.001). There was neither any correlation between EEG latency and mRS (rho 0.087, p 0.236), nor with CPC (rho = 0.027, p = 0.603). CONCLUSION: This analysis shows no correlation between delays of EEG recordings and mortality or functional outcomes at 6 months in critically ill adults. SIGNIFICANCE: These findings might suggest that in critically ill adults mortality correlates with underlying brain injury rather than EEG delay.

Continuous Versus Routine Standardized Electroencephalogram for Outcome Prediction in Critically Ill Adults: Analysis From a Randomized Trial.

OBJECTIVES: To investigate electroencephalogram (EEG) features' relation with mortality or functional outcome after disorder of consciousness, stratifying patients between continuous EEG and routine EEG. DESIGN: Retrospective analysis of data from a randomized controlled trial. SETTING: Multiple adult ICUs. PATIENTS: Data from 364 adults with acute disorder of consciousness, randomized to continuous EEG (30-48 hr; n = 182) or repeated 20-minute routine electroencephalogram (n = 182). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between electrographic features and mortality and modified Rankin scale at 6 months (good 0-2) were assessed. Background continuity, higher frequency, and reactivity correlated with survival and good modified Rankin scale. Rhythmic and periodic patterns carried dual prognostic information: lateralized periodic discharges were associated with mortality and bad modified Rankin scale. Generalized rhythmic delta activity correlated with survival, good modified Rankin scale, and lower occurrence of status epilepticus. Presence of sleep-spindles and continuous EEG background was associated with good outcome in the continuous EEG subgroup. In the routine EEG group, a model combining background frequency, continuity, reactivity, sleep-spindles, and lateralized periodic discharges was associated with mortality at 70.91% (95% CI, 59.62-80.10%) positive predictive value and 63.93% (95% CI, 58.67-68.89%) negative predictive value. In the continuous EEG group, a model combining background continuity, reactivity, generalized rhythmic delta activity, and lateralized periodic discharges was associated with mortality at 84.62% (95%CI, 75.02-90.97) positive predictive value and 74.77% (95% CI, 68.50-80.16) negative predictive value. CONCLUSIONS: Standardized EEG interpretation provides reliable prognostic information. Continuous EEG provides more information than routine EEG.

EEG spindles integrity in critical care adults. Analysis of a randomized trial.

OBJECTIVES: Occurrence of EEG spindles has been recently associated with favorable outcome in ICU patients. Available data mostly rely on relatively small patients' samples, particular etiologies, and limited variables ascertainment. We aimed to expand previous findings on a larger dataset, to identify clinical and EEG patterns correlated with spindle occurrence, and explore its prognostic implications. METHODS: Retrospective observational study of prospectively collected data from a randomized trial (CERTA, NCT03129438) assessing the relationship of continuous (cEEG) versus repeated routine EEG (rEEG) with outcome in adults with acute consciousness impairment. Spindles were prospectively assessed visually as 12-16Hz activity on fronto-central midline regions, at any time during EEG interventions. Uni- and multivariable analyses explored correlations between spindles occurrence, clinical and EEG variables, and outcome (modified Rankin Scale, mRS; mortality) at 6 months. RESULTS: Among the analyzed 364 patients, spindles were independently associated with EEG background reactivity (OR 13.2, 95% CI: 3.11-56.26), and cEEG recording (OR 4.35, 95% CI: 2.5 - 7.69). In the cEEG subgroup (n=182), 33.5% had spindles. They had better FOUR scores (p=0.004), fewer seizures or status epilepticus (p=0.02), and lower mRS (p=0.02). Mortality was reduced (p=0.002), and independently inversely associated with spindle occurrence (OR 0.50, CI 95% 0.25-0.99) and increased EEG background continuity (OR 0.16, 95% CI: 0.07 - 0.41). CONCLUSIONS: Besides confirming that spindle activity occurs in up to one third of acutely ill patients and is associated with better outcome, this study shows that cEEG has a higher yield than rEEG in identifying them. Furthermore, it unravels associations with several clinical and EEG features in this clinical setting.

Electroencephalography of mechanically ventilated patients at high risk of delirium.

OBJECTIVE: Neurophysiological exploration of ICU delirium is limited. Here, we examined EEG characteristics of medical-surgical critically ill patients with new-onset altered consciousness state at high risk for ICU delirium. MATERIALS AND METHODS: Pre-planned analysis of non-neurological mechanically ventilated medical-surgical ICU subjects, who underwent a prospective multicenter randomized, controlled EEG study (NCT03129438, April 2017-November 2018). EEG characteristics, according to the 2012 ACNS nomenclature, included background activity, rhythmic periodic patterns/epileptic activity, amplitude, frequency, stimulus-induced discharges, triphasic waves, reactivity, and NREM sleep. We explored EEG findings in delirious versus non-delirious patients, specifically focusing on the presence of burst-suppression and rhythmic periodic patterns (ictal-interictal continuum), and ictal activity. RESULTS: We analyzed 91 patients (median age, 66 years) who underwent EEG because of new-onset altered consciousness state at a median 5 days from admission; 42 patients developed delirium (46%). Burst-suppression (10 vs 0%, p = .02), rhythmic/periodic patterns (43% vs 22%, p = .03) and epileptiform activity (7 vs 0%, p = .05) were more frequent in delirious versus non-delirious patients. The presence of at least one of these abnormal EEG findings (32/91 patients; 35%) was associated with a significant increase in the likelihood of delirium (42 vs 15%, p = .006). Cumulative dose of sedatives and analgesics, as well as all other EEG characteristics, did not differ significantly between the two groups. CONCLUSION: In mechanically ventilated non-neurological critically ill patients with new-onset alteration of consciousness, EEG showing burst-suppression, rhythmic or periodic patterns, or seizures/status epilepticus indicate an increased risk of ICU delirium.

Severe Neuroexcitatory Reaction: A Rare and Underrecognized Life-Threatening Complication of Propofol-Induced Anesthesia.

We describe a case of severe neuroexcitatory reaction with hyperthermia after administration of propofol in a 43-year-old patient suspected of a relapse of sarcoidosis who underwent bronchoscopy. This resulted in a lengthy stay in intensive care and long-term neuropsychological impairment. A review of the literature shows that severe neuroexcitatory symptoms (seizure-like phenomena, abnormal hypertonic, and/or jerky movements) occur rarely after propofol administration and may be life-threatening. Due to the paucity of data, the treatment is mostly empirical. The diagnosis can also be delayed owing to underrecognition. We conclude that health practitioners who frequently use propofol should be aware of this specific manifestation of drug toxicity, which albeit rare can be devastating for the patient.

Continuous versus routine EEG in critically ill adults: reimbursement analysis of a randomised trial.

BACKGROUND: Continuous EEG (cEEG) is increasingly used in critically ill patients, but it is more resource-intensive than routine EEG (rEEG). In the US, cEEG generates increased hospitalisation charges. This study analysed hospital-related reimbursement for participants in a Swiss multicentre randomised controlled trial that assessed the relationship of cEEG versus repeated rEEG with outcome. METHODS: We used data of the CERTA study (NCT03129438), including demographics, clinical variables and reimbursement for acute hospitalisations after the Swiss Diagnosis Related Groups billing system. In addition to a comparison between EEG intervention groups, we explored correlations with several clinical variables, using uni- and multivariate analyses. RESULTS: In total, 366 adults were analysed (184 cEEG, 182 rEEG); 123 (33.6%) were women, mean age was 63.8 years (± 15). Median hospitalisation reimbursement was comparable across EEG groups in univariate analysis: cEEG CHF 89,631 (interquartile range [IQR] 45,635–159,994); rEEG CHF 73,017 (IQR 43,031–158,565); p = 0.432. However, multivariate regression disclosed that increasing reimbursement mostly correlated with longer acute hospitalisation (p <0.001), but also with cEEG (p = 0.019) and lack of seizure / status epilepticus detection (a surrogate of survival, p = 0.036). CONCLUSION: In a Swiss Diagnosis Related Groups billing system applied to critically ill adults, reimbursement largely depends on duration of acute hospital stay, whereas cEEG and lack of seizure/ status epilepticus detection also contribute to the bill. This differs from the USA, where charges are directly increased by cEEG.

Update on the management of status epilepticus.

PURPOSE OF REVIEW: Randomized controlled trials investigating the initial pharmacological treatment of status epilepticus have been recently published. Furthermore, status epilepticus arising in comatose survivors after cardiac arrest has received increasing attention in the last years. This review offers an updated assessment of status epilepticus treatment in these different scenarios. RECENT FINDINGS: Initial benzodiazepines underdosing is common and correlates with development of status epilepticus refractoriness. The recently published ESETT trial provides high-level evidence regarding the equivalence of fosphenytoin, valproate, and levetiracetam as a second-line option. Myoclonus or epileptiform transients on electroencephalography occur in up to 1/3 of patients surviving a cardiac arrest. Contrary to previous assumptions regarding an almost invariable association with death, at least 1/10 of them may awaken with reasonably good prognosis, if treated. Multimodal prognostication including clinical examination, EEG, somatosensory evoked potentials, biochemical markers, and neuroimaging help identifying patients with a chance to recover consciousness, in whom a trial with antimyoclonic compounds and at times general anesthetics is indicated. SUMMARY: There is a continuous, albeit relatively slow progress in knowledge regarding different aspect of status epilepticus; recent findings refine some treatment strategies and help improving patients' outcomes. Further high-quality studies are clearly needed to further improve the management of these patients, especially those with severe, refractory status epilepticus forms.

Informed consent in critically ill adults participating to a randomized trial.

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.

Epidemiology of status epilepticus in a non-urban area in Switzerland.

OBJECTIVE: The aim of this study is to provide a precise population-based data on incidence, types, and causes of SE according to the 2015 ILAE definition and classification using a prospectively cohort in an adult population of a non-urban area. MATERIALS & METHODS: Prospective observational SE cohort in a single large community hospital. The center is the only one in the region (French-speaking Valais canton), with all available resources to treat SE (including neurologist available 24/7, EEG monitoring and ICU). Every adult patient with SE is included (except post-anoxic SE). All variables are collected prospectively using the 2015 ILAE status epilepticus classification. RESULTS: We identified 103 patients with SE in the study period between 1st of May 2015 and 30th of June 2019 for a population of 260,855 people. The incidence is 8.6 per 100,000 adults per year with an overall case-fatality rate of 7.8%. SE was generalized convulsive in 52% of cases and nonconvulsive SE in coma in 34%. CONCLUSIONS: Using a prospective reliable data collection with strict inclusion criteria, we found an incidence of 8.6 per 100,000 persons per year, in line with previous report using similar methods. The most severe forms-generalized convulsive and nonconvulsive SE in coma-represent the majority of cases. These data might be important for resources allocation in non-urban area with non-university healthcare system.