Recent advances in clinical electroencephalography.

PURPOSE OF REVIEW: Clinical electroencephalography (EEG) is a conservative medical field. This explains likely the significant gap between clinical practice and new research developments. This narrative review discusses possible causes of this discrepancy and how to circumvent them. More specifically, we summarize recent advances in three applications of clinical EEG: source imaging (ESI), high-frequency oscillations (HFOs) and EEG in critically ill patients. RECENT FINDINGS: Recently published studies on ESI provide further evidence for the accuracy and clinical utility of this method in the multimodal presurgical evaluation of patients with drug-resistant focal epilepsy, and opened new possibilities for further improvement of the accuracy. HFOs have received much attention as a novel biomarker in epilepsy. However, recent studies questioned their clinical utility at the level of individual patients. We discuss the impediments, show up possible solutions and highlight the perspectives of future research in this field. EEG in the ICU has been one of the major driving forces in the development of clinical EEG. We review the achievements and the limitations in this field. SUMMARY: This review will promote clinical implementation of recent advances in EEG, in the fields of ESI, HFOs and EEG in the intensive care.

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.

Auditory stimulation and deep learning predict awakening from coma after cardiac arrest.

Assessing the integrity of neural functions in coma after cardiac arrest remains an open challenge. Prognostication of coma outcome relies mainly on visual expert scoring of physiological signals, which is prone to subjectivity and leaves a considerable number of patients in a 'grey zone', with uncertain prognosis. Quantitative analysis of EEG responses to auditory stimuli can provide a window into neural functions in coma and information about patients' chances of awakening. However, responses to standardized auditory stimulation are far from being used in a clinical routine due to heterogeneous and cumbersome protocols. Here, we hypothesize that convolutional neural networks can assist in extracting interpretable patterns of EEG responses to auditory stimuli during the first day of coma that are predictive of patients' chances of awakening and survival at 3 months. We used convolutional neural networks (CNNs) to model single-trial EEG responses to auditory stimuli in the first day of coma, under standardized sedation and targeted temperature management, in a multicentre and multiprotocol patient cohort and predict outcome at 3 months. The use of CNNs resulted in a positive predictive power for predicting awakening of 0.83 ± 0.04 and 0.81 ± 0.06 and an area under the curve in predicting outcome of 0.69 ± 0.05 and 0.70 ± 0.05, for patients undergoing therapeutic hypothermia and normothermia, respectively. These results also persisted in a subset of patients that were in a clinical 'grey zone'. The network's confidence in predicting outcome was based on interpretable features: it strongly correlated to the neural synchrony and complexity of EEG responses and was modulated by independent clinical evaluations, such as the EEG reactivity, background burst-suppression or motor responses. Our results highlight the strong potential of interpretable deep learning algorithms in combination with auditory stimulation to improve prognostication of coma outcome.

Continuous versus Routine Electroencephalography in the Intensive Care Unit: A Review of Current Evidence.

BACKGROUND: Electroencephalography (EEG) has long been used to detect seizures in patients with disorders of consciousness. In recent years, there has been a drastically increased adoption of continuous EEG (cEEG) in the intensive care units (ICUs). Given the resources necessary to record and interpret cEEG, this is still not available in every center and widespread recommendations to use continuous instead of routine EEG (typically lasting 20 min) are still a matter of some debate. Considering recent literature and personal experience, this review offers a rationale and practical advice to address this question. SUMMARY: Despite the development of increasingly performant imaging techniques and several validated biomarkers, EEG remains central to clinicians in the intensive care unit and has been experiencing expanding popularity for at least 2 decades. Not only does EEG allow seizure or status epilepticus detection, which in the ICU often present without clinical movements, but it is also paramount for the prognostic evaluation of comatose patients, especially after cardiac arrest, and for detecting delayed ischemia after subarachnoid hemorrhage. At the end of the last Century, improvements of technical and digital aspects regarding recording and storage of EEG tracings have progressively led to the era of cEEG and automated quantitative analysis. KEY MESSAGES: As compared to repeated rEEG, cEEG in comatose patients does not seem to improve clinical prognosis to a relevant extent, despite allowing a more performant of detection ictal events and consequent therapeutic modifications. The choice between cEEG and rEEG must therefore always be patient-tailored.

Relevance of Continuous EEG versus Routine EEG for Outcome Prediction after Traumatic Brain Injury.

INTRODUCTION: In a cohort of adult patients with disturbance of consciousness after TBI, we aimed to explore the relationship of continuous video-EEG (cEEG) versus routine EEG (rEEG) with mortality and functional outcome. METHODS: This is a post hoc analysis of a randomized controlled trial (CERTA), in which adults with disorder of consciousness and needing EEG (excluding those with proven seizures/SE just before) were randomized 1:1 to cEEG or two rEEG. In TBI patients, correlation between EEG duration, mortality, and modified Rankin score (mRs, good 0-2) at 6 months was assessed. RESULTS: Among 364 patients, 44 presenting with consciousness impairment after TBI were included; 29 randomized to cEEG and 15 to rEEG. Mortality (p = 0.88) and functional outcome (p = 0.58) at 6 months were similar between groups. There was a nonsignificant tendency toward more seizure/status epilepticus detection with cEEG (p = 0.08). In multivariable regression, cEEG was not related to functional outcome (OR: 0.75 [0.13-4.24], p = 0.745) or mortality (OR: 7.11 [0.51-99.32], p = 0.145). CONCLUSION: Despite allowing increased seizure detections in TBI patients, cEEG does not seem to be associated with better functional outcome or mortality over rEEG. Pending larger trials, repeated rEEG might be acceptable in post-TBI disorder of consciousness, especially in resource-limited environments.

Multimodal Prediction of Favorable Outcome After Cardiac Arrest: A Cohort Study.

OBJECTIVES: Prognostic guidelines after cardiac arrest (CA) focus on unfavorable outcome prediction; favorable outcome prognostication received less attention. Our aim was to identify favorable outcome predictors and combine them into a multimodal model. DESIGN: Retrospective analysis of prospectively collected data (January 2016 to June 2021). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Brigham and Women's Hospital, Boston, MA). PATIENTS: Four hundred ninety-nine consecutive comatose adults admitted after CA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CA variables (initial rhythm, time to return of spontaneous circulation), clinical examination (Full Outline of UnResponsiveness [FOUR] score at 72 hr, early myoclonus), electroencephalography (EEG) (reactivity, continuity, epileptiform features, and prespecified highly malignant patterns), somatosensory-evoked potentials, quantified pupillometry, and serum neuron-specific enolase (NSE) were retrieved. Neurologic outcome was assessed at 3 months using Cerebral Performance Category (CPC); 1 and 2 were considered as favorable outcome. Predictive performance of each variable toward favorable outcomes were calculated, and most discriminant items were combined to obtain a multimodal prognostic score, using multivariable ordinal logistic regression, receiving operator characteristic curves, and cross-validation. Our analysis identified a prognostic score including six modalities (1 point each): 1) early (12-36 hr) EEG not highly malignant, 2) early EEG background reactivity, 3) late (36-72 hr) EEG background reactivity and 4) continuity, 5) peak serum NSE within 48 hours less than or equal to 41 µg/L, and 6) FOUR score greater than or equal to 5 at 72 hours. At greater than or equal to 4 out of 6 points, sensitivity for CPC 1-2 was 97.5% (95% CI, 92.9-99.5%) and accuracy was 77.5% (95% CI, 72.7-81.8%); area under the curve was 0.88 (95% CI, 0.85-0.91). The score showed similar performances in the validation cohort. CONCLUSIONS: This study describes and externally validates a multimodal score, including clinical, EEG and biological items available within 72 hours, showing a high performance in identifying early comatose CA survivors who will reach functional independence at 3 months.

Status epilepticus prognosis following levetiracetam administration: Analysis of loading doses.

BACKGROUND AND PURPOSE: Recommended loading doses of levetiracetam (LEV) for status epilepticus (SE) treatment have increased over time. However, this was not evidence-based, and the benefit of the increase remains unclear. The effect of different LEV loading doses on SE prognosis was explored. METHODS: This is a retrospective analysis of an SE adult registry (January 2016-December 2021), including patients receiving LEV as a second-line SE treatment. Patients were stratified according to LEV loading doses (threshold 35 mg/kg). Main outcomes were global mortality, LEV use as last SE treatment, and return to baseline conditions at discharge, exploring LEV as a dichotomized or continuous dose. RESULTS: Among 202 patients, 44 received LEV at ≥35 mg/kg and 158 below it. Global mortality, adjusted for SE severity and potentially fatal aetiology, was more frequent in the high LEV dose group (27.2% vs. 17.1%, odds ratio 3.14, 95% confidence interval 1.23-8.06; p = 0.017), whilst LEV prescription as last treatment and return to baseline conditions were comparable. Considering continuous LEV dosages or mortality in ongoing SE, however, no outcome reached statistical significance. CONCLUSIONS: Lower LEV loading doses do not seem to correlate with worse clinical outcome, challenging current guidelines. Further studies, ideally prospective, are needed on this topic.

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.

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

BACKGROUND AND PURPOSE: Intravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE. METHODS: This was a retrospective study in one referral center of all consecutive VPA-naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics. RESULTS: Among 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7-58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg. CONCLUSIONS: A high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25-30 mg/kg appears adequate in SE.

Ketamine in adult super-refractory status epilepticus: Efficacy analysis on a prospective registry.

BACKGROUND: Status epilepticus (SE) persisting despite two anti-seizures medications (ASM) and anesthetics is labeled super refractory (SRSE), correlating with important morbidity and mortality. Its treatment relies on expert opinions. Due to its pharmacological properties, ketamine (KET) has received increasing attention, but data are essentially retrospective. AIMS: To describe an unselected cohort of adults receiving KET for SRSE. METHODS: Analysis of a prospective registry of consecutive SE episodes, identifying SRSE patients receiving ketamine (KET). Comparison with recent adult series including more than 10 patients. RESULTS: Eleven patients received KET after a median of 4 days (range: 2-20); median dose was 5 mg/kg/h (range: 2.5-15). KET provided permanent SE control in three (27%). Previous series, using KET administration delays and doses similar to our cohort, report KET efficacy in 28-96% of cases. CONCLUSIONS: We found a lower SE control rate than existing literature, whose data are, however, often retrospective, potentially selecting patients with less severe SE forms or responding to KET. This might explain outcome differences, as KET administration modalities were comparable with our cohort. Since randomized controlled studies are lacking on this subject, the analysis of this prospective, unselected cohort, if confirmed, suggests a current overestimation of KET efficacy in SRSE.

Treatment-emergent adverse events and antiseizure medication actual drug load.

OBJECTIVE: The correlation between treatment-emergent adverse events (TEAE) and antiseizure medication (ASM) drug load is a controversial topic. Previous studies used daily defined dosage (DDD) to measure drug load. We aim to assess if ASM adjusted to body weight and plasma levels were associated with TEAE. METHODS: We analyzed clinical visits of a trial on therapeutic drug monitoring in outpatients with epilepsy. TEAE, treatment, and its changes, as well as ASM plasma levels, were recorded at each visit. Each medication level was stratified according to its position in relation to its proposed reference range (below, in the lower half, upper half, or above). RESULTS: We analyzed 424 visits (151 participants). Treatment-emergent adverse events were reported in 84 (20%) visits. There was no significant difference when comparing visits with TEAE with those without TEAE in terms of ASM drug load (calculated with DDD), corrected for body weight, their changes since the last visit, as well as summed plasma levels compared to reference ranges. SIGNIFICANCE: Actual drug load seems not to represent a major determinant of TEAE recorded during routine visits, even when accounting thoroughly for the patient's exposure to the treatment. The use of structured questionnaires and neuropsychometric tests may assess more accurately the potential consequences of drug loads.

Neuroprognostication Under ECMO After Cardiac Arrest: Are Classical Tools Still Performant?

BACKGROUND: According to international guidelines, neuroprognostication in comatose patients after cardiac arrest (CA) is performed using a multimodal approach. However, patients undergoing extracorporeal membrane oxygenation (ECMO) may have longer pharmacological sedation and show alteration in biological markers, potentially challenging prognostication. Here, we aimed to assess whether routinely used predictors of poor neurological outcome also exert an acceptable performance in patients undergoing ECMO after CA. METHODS: This observational retrospective study of our registry includes consecutive comatose adults after CA. Patients deceased within 36 h and not undergoing prognostic tests were excluded. Veno-arterial ECMO was initiated in patients < 80 years old presenting a refractory CA, with a no flow < 5 min and a low flow ≤ 60 min on admission. Neuroprognostication test performance (including pupillary reflex, electroencephalogram, somatosensory-evoked potentials, neuron-specific enolase) toward mortality and poor functional outcome (Cerebral Performance Categories [CPC] score 3-5) was compared between patients undergoing ECMO and those without ECMO. RESULTS: We analyzed 397 patients without ECMO and 50 undergoing ECMO. The median age was 65 (interquartile range 54-74), and 69.8% of patients were men. Most had a cardiac etiology (67.6%); 52% of the patients had a shockable rhythm, and the median time to return of an effective circulation was 20 (interquartile range 10-28) minutes. Compared with those without ECMO, patients receiving ECMO had worse functional outcome (74% with CPC scores 3-5 vs. 59%, p = 0.040) and a nonsignificant higher mortality (60% vs. 47%, p = 0.080). Apart from the neuron-specific enolase level (higher in patients with ECMO, p < 0.001), the presence of prognostic items (pupillary reflex, electroencephalogram background and reactivity, somatosensory-evoked potentials, and myoclonus) related to unfavorable outcome (CPC score 3-5) in both groups was similar, as was the prevalence of at least any two such items concomitantly. The specificity of each these variables toward poor outcome was between 92 and 100% in both groups, and of the combination of at least two items, it was 99.3% in patients without ECMO and 100% in those with ECMO. The predictive performance (receiver operating characteristic curve) of their combination toward poor outcome was 0.822 (patients without ECMO) and 0.681 (patients with ECMO) (p = 0.134). CONCLUSIONS: Pending a prospective assessment on a larger cohort, in comatose patients after CA, the performance of prognostic factors seems comparable in patients with ECMO and those without ECMO. In particular, the combination of at least two poor outcome criteria appears valid across these two groups.

Complementary roles of neural synchrony and complexity for indexing consciousness and chances of surviving in acute coma.

An open challenge in consciousness research is understanding how neural functions are altered by pathological loss of consciousness. To maintain consciousness, the brain needs synchronized communication of information across brain regions, and sufficient complexity in neural activity. Coordination of brain activity, typically indexed through measures of neural synchrony, has been shown to decrease when consciousness is lost and to reflect the clinical state of patients with disorders of consciousness. Moreover, when consciousness is lost, neural activity loses complexity, while the levels of neural noise, indexed by the slope of the electroencephalography (EEG) spectral exponent decrease. Although these properties have been well investigated in resting state activity, it remains unknown whether the sensory processing network, which has been shown to be preserved in coma, suffers from a loss of synchronization or information content. Here, we focused on acute coma and hypothesized that neural synchrony in response to auditory stimuli would reflect coma severity, while complexity, or neural noise, would reflect the presence or loss of consciousness. Results showed that neural synchrony of EEG signals was stronger for survivors than non-survivors and predictive of patients' outcome, but indistinguishable between survivors and healthy controls. Measures of neural complexity and neural noise were not informative of patients' outcome and had high or low values for patients compared to controls. Our results suggest different roles for neural synchrony and complexity in acute coma. Synchrony represents a precondition for consciousness, while complexity needs an equilibrium between high or low values to support conscious cognition.

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.

Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment.

OBJECTIVE: Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy. METHODS: We performed a randomized, controlled trial comparing systematic with rescue TDM of lamotrigine, levetiracetam, oxcarbazepine, topiramate, brivaracetam, zonisamide, or pregabalin. Participants were adults with epilepsy, in whom treatment with newer generation AEDs was initiated or needed adjustment. In the systematic TDM arm, AED plasma levels were available at each appointment, whereas in the rescue TDM arm, levels were known only if a study endpoint was reached (inefficacy or adverse events). The primary outcome was the proportion of participants followed 1 year without reaching one of the predefined endpoints. RESULTS: A total of 151 participants were enrolled; global retention in the study was similar in both arms (56% overall, 58% in the systematic, and 53% in the rescue TDM arm, p = 0.6, Cox regression). There was no difference in terms of outcome regarding treatment efficacy or tolerability. Partial adherence of clinicians to TDM (adjusting or not AED dosage based on blood levels) did not explain this lack of benefit. INTERPRETATION: This study provides class A evidence that systematic drug level monitoring of newer generation AEDs does not bring tangible benefits in the management of patients with epilepsy. Poor correlation between clinical effects and drug levels likely accounts for this finding. However, TDM is useful in several situations, such as pregnancy, as well as when there are compliance issues. ANN NEUROL 2020;87:22-29.

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.

Seizure freedom and plasma levels of newer generation antiseizure medications.

OBJECTIVES: Contrary to older antiseizure medications (ASM), correlation between plasma levels and seizure freedom is not well defined for newer generation ASM. We assessed correlations between efficacy and newer generation ASM plasma levels in patients with epilepsy. MATERIALS AND METHODS: Plasma medication levels were measured over two years in consecutive patients taking lamotrigine, levetiracetam, oxcarbazepine, topiramate, zonisamide, lacosamide, perampanel or pregabalin. Seizure freedom was defined as three times the longest inter-seizure pre-treatment interval, or at least one year. Each medication level was stratified according to its position in relation to its proposed reference range (below or in lower half vs upper half or above). RESULTS: 168 patients on stable therapy were included. ASM plasma levels of seizure-free patients were lower than those with ongoing seizures; 45/48 (93.7%) were in the lower half or below the reference ranges, compared to 86/106 (81.1%; p = .004). Lamotrigine plasma levels were significantly lower in seizure-free patients (median 2.4 mg/L range 0.4-6.5 mg/L, none above 6.5 mg/L) compared with those with ongoing seizures (5 mg/L, 0.5-14.2 mg/L; p < .0001). Levetiracetam showed similar results (7.2 mg/L, 1.6-15.1 mg/L; none above 15.1 mg/L in seizure-free patients vs 16.4 mg/L, 0.6-47.7 mg/L; p = .005). Demographics, epilepsy type and polytherapy did not influence the results. CONCLUSIONS: Efficacy of newer generation ASMs seems to be reached at the lower part or at times even below the reference ranges in drug responsive patients; this could inform regarding titrations of these treatments.

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.

[Recent Advances in Neurology]. / Neurologie.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease.

L'année 2020 a vu d'importantes avancées dans le domaine des biomarqueurs sanguins pour le diagnostic biologique de la maladie d'Alzheimer. Plusieurs études permettent de mieux définir la prise en charge de l'épilepsie chez la femme en âge de procréer et de l'état de mal épileptique. Les nouvelles recommandations suisses pour la prise en charge préhospitalière de l'AVC aigu sont en cours de publication, tout comme de nouvelles cibles pour leur prévention secondaire. De nombreuses avancées concernant la prise en charge des Neuromyelitis Optica Spectrum Disorder ont été publiées. Divers tableaux neurologiques (centraux et périphériques) liés à la pandémie de Covid-19 ont été décrits. Plusieurs études ont permis de confirmer l'efficacité des nouveaux traitements de la migraine (notamment les anti-Calcitonin Gene-Related Peptide). Enfin, de nouvelles thérapies pharmacologiques sont disponibles pour la maladie de Parkinson.

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.