Disclosing the Risk Associated with Isolated REM Behavior Disorder: The Sleep Experts' Perspective.

BACKGROUND: Isolated rapid-eye-movement sleep behavior disorder (iRBD) is associated with a high risk for phenoconversion to a neurodegenerative disorder, but the optimal approach for disclosure of this risk to patients is still debated. OBJECTIVES: The aim of this study was to explore views and experiences of iRBD experts regarding risk disclosure. METHODS: In this qualitative study, semi-structured interviews with sleep experts caring for patients with iRBD were analyzed through a conventional content analysis approach. RESULTS: We interviewed 22 iRBD experts (eight female, average age of 51.8 years) from 18 Italian sleep centers; 21/22 regularly disclosed the risks associated with iRBD, usually after the video-polysomnography, and 8/22 regularly mentioned phenoconversion rates. Content analysis allowed us to identify three main themes. First, sleep experts reported several points in favor of risk disclosure, especially related to the principle of beneficence, but some highlighted the need for specific learning on the topic. Second, experts favored a patient-tailored disclosure that should not upset the patient unnecessarily, since phenoconversion is uncertain. Third, risk disclosure was seen by participants as a relational task that should be carried out in person in the context of a trusting patient-physician relationship, while they had contrasting views regarding patients' previous knowledge. CONCLUSIONS: Sleep experts generally preferred a tailored and reassuring approach to risk disclosure within a framework of relational autonomy. The results of this study indicate the need for specific education, training, and recommendations concerning risk disclosure that should also include patients' and families' preferences.

[Neurology: what's new in 2023]. / Neurologie: ce qui a changé en 2023.

The year 2023 is marked by the arrival on the market of lecanemab for the treatment of Alzheimer's disease. New biomarkers have demonstrated their usefulness in monitoring peripheral neuropathies and diagnosing synucleinopathies. A genetic study has highlighted the role of nervous system cells in the risk of progression of multiple sclerosis (MS). The adverse effects of anticonvulsant treatments after prenatal exposure and on lipid metabolism have been clarified. New anti-CGRP treatments have demonstrated their efficacy in migraine attacks and chronic migraines. The criteria for thrombectomy have been further broadened. And finally, rehabilitation is refining the management of cerebrovascular patients and those with secondary progressive MS.

L'année 2023 est marquée par l'arrivée sur le marché du lécanémab pour le traitement de la maladie d'Alzheimer. De nouveaux biomarqueurs ont démontré leur utilité dans le suivi des neuropathies périphériques ou dans le diagnostic des synucléinopathies. Une étude génétique a mis en évidence le rôle des cellules du système nerveux dans le risque de progression de la sclérose en plaques (SEP). Les effets indésirables des traitements anticonvulsivants lors d'exposition prénatale ou sur le métabolisme des lipides ont été précisés. De nouveaux traitements anti-CGRP ont démontré leur efficacité dans les crises migraineuses et les migraines chroniques. Les critères de thrombectomie se sont encore élargis. Et enfin, la réhabilitation affine la prise en charge des patients cérébrovasculaires et de ceux atteints d'une SEP secondaire progressive.

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.

The predictive value of highly malignant EEG patterns after cardiac arrest: evaluation of the ERC-ESICM recommendations.

PURPOSE: The 2021 guidelines endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend using highly malignant electroencephalogram (EEG) patterns (HMEP; suppression or burst-suppression) at > 24 h after cardiac arrest (CA) in combination with at least one other concordant predictor to prognosticate poor neurological outcome. We evaluated the prognostic accuracy of HMEP in a large multicentre cohort and investigated the added value of absent EEG reactivity. METHODS: This is a pre-planned prognostic substudy of the Targeted Temperature Management trial 2. The presence of HMEP and background reactivity to external stimuli on EEG recorded > 24 h after CA was prospectively reported. Poor outcome was measured at 6 months and defined as a modified Rankin Scale score of 4-6. Prognostication was multimodal, and withdrawal of life-sustaining therapy (WLST) was not allowed before 96 h after CA. RESULTS: 845 patients at 59 sites were included. Of these, 579 (69%) had poor outcome, including 304 (36%) with WLST due to poor neurological prognosis. EEG was recorded at a median of 71 h (interquartile range [IQR] 52-93) after CA. HMEP at > 24 h from CA had 50% [95% confidence interval [CI] 46-54] sensitivity and 93% [90-96] specificity to predict poor outcome. Specificity was similar (93%) in 541 patients without WLST. When HMEP were unreactive, specificity improved to 97% [94-99] (p = 0.008). CONCLUSION: The specificity of the ERC-ESICM-recommended EEG patterns for predicting poor outcome after CA exceeds 90% but is lower than in previous studies, suggesting that large-scale implementation may reduce their accuracy. Combining HMEP with an unreactive EEG background significantly improved specificity. As in other prognostication studies, a self-fulfilling prophecy bias may have contributed to observed results.

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.

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.

Status epilepticus in the ICU.

Status epilepticus (SE) is a common medical emergency associated with significant morbidity and mortality. Management that follows published guidelines is best suited to improve outcomes, with the most severe cases frequently being managed in the intensive care unit (ICU). Diagnosis of convulsive SE can be made without electroencephalography (EEG), but EEG is required to reliably diagnose nonconvulsive SE. Rapidly narrowing down underlying causes for SE is crucial, as this may guide additional management steps. Causes may range from underlying epilepsy to acute brain injuries such as trauma, cardiac arrest, stroke, and infections. Initial management consists of rapid administration of benzodiazepines and one of the following non-sedating intravenous antiseizure medications (ASM): (fos-)phenytoin, levetiracetam, or valproate; other ASM are increasingly used, such as lacosamide or brivaracetam. SE that continues despite these medications is called refractory, and most commonly treated with continuous infusions of midazolam or propofol. Alternatives include further non-sedating ASM and non-pharmacologic approaches. SE that reemerges after weaning or continues despite management with propofol or midazolam is labeled super-refractory SE. At this step, management may include non-sedating or sedating compounds including ketamine and barbiturates. Continuous video EEG is necessary for the management of refractory and super-refractory SE, as these are almost always nonconvulsive. If possible, management of the underlying cause of seizures is crucial particularly for patients with autoimmune encephalitis. Short-term mortality ranges from 10 to 15% after SE and is primarily related to increasing age, underlying etiology, and medical comorbidities. Refractoriness of treatment is clearly related to outcome with mortality rising from 10% in responsive cases, to 25% in refractory, and nearly 40% in super-refractory SE.

Outcome of comatose patients following cardiac arrest: When mRS completes CPC.

AIM: Good outcome in patients following cardiac arrest (CA) is usually defined as Cerebral Performance Category (CPC) 1-2, while CPC 3 is debated, and CPC 4-5 represent poor outcome. We aimed to assess when the modified Rankin Scale (mRS) can improve CPC outcome description, especially in CPC 3. We further aimed to correlate neuron specific enolase (NSE) with both functional measures to explore their relationship with neuronal damage. METHODS: Peak NSE within the first 48 hours, and CPC and mRS at 3 months were prospectively collected for 665 consecutive comatose adults following CA treated between April 2016 and April 2023. For each CPC category, mRS was described. We considered good outcome as mRS 1-3, in line with existing recommendations. CPC and mRS were correlated to peak serum NSE using non-parametric assessments. RESULTS: CPC 1, 2, 4 and 5 correlated almost perfectly with mRS in terms of good and poor outcomes. However, CPC 3 was heterogeneously associated to the dichotomized mRS (53.1% had good outcome (mRS 0-3), 46.9% poor outcome (mRS 4-6)). NSE was strongly correlated with CPC (Spearman's rho 0.616, P < 0.001) and mRS (Spearman's rho 0.613, P < 0.001). CONCLUSION: CPC and mRS correlate similarly with neuronal damage. Whilst CPC 1-2 and CPC 4-5 are strongly associated with mRS 0-3 and, respectively, with mRS 5-6, CPC 3 is heterogenous: both good and poor mRS scores are found within this category. Therefore, we suggest that the mRS should be routinely assessed in patients with CPC 3 to refine outcome description.

The effect of sedation and time after cardiac arrest on coma outcome prognostication based on EEG power spectra.

Early prognostication of long-term outcome of comatose patients after cardiac arrest remains challenging. Electroencephalography-based power spectra after cardiac arrest have been shown to help with the identification of patients with favourable outcome during the first day of coma. Here, we aim at comparing the power spectra prognostic value during the first and second day after coma onset following cardiac arrest and to investigate the impact of sedation on prognostication. In this cohort observational study, we included comatose patients (N = 91) after cardiac arrest for whom resting-state electroencephalography was collected on the first and second day after cardiac arrest in four Swiss hospitals. We evaluated whether the average power spectra values at 4.6-15.2 Hz were predictive of patients' outcome based on the best cerebral performance category score at 3 months, with scores ranging from 1 to 5 and dichotomized as favourable (1-2) and unfavourable (3-5). We assessed the effect of sedation and its interaction with the electroencephalography-based power spectra on patient outcome prediction through a generalized linear mixed model. Power spectra values provided 100% positive predictive value (95% confidence intervals: 0.81-1.00) on the first day of coma, with correctly predicted 18 out of 45 favourable outcome patients. On the second day, power spectra values were not predictive of patients' outcome (positive predictive value: 0.46, 95% confidence intervals: 0.19-0.75). On the first day, we did not find evidence of any significant contribution of sedative infusion rates to the patient outcome prediction (P > 0.05). Comatose patients' outcome prediction based on electroencephalographic power spectra is higher on the first compared with the second day after cardiac arrest. Sedation does not appear to impact patient outcome prediction.

Acute Valproate-Induced Encephalopathy in Status Epilepticus: A Registry-Based Assessment.

BACKGROUND: Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown. OBJECTIVE: The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients. METHODS: We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment. RESULTS: Patients had a mean valproate intravenous loading dose of 34.5 mg/kg and a mean maintenance dose of 15.3 mg/kg/d (1078 mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p = 0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone). CONCLUSION: Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases.

Clonazepam Loading Dose in Status Epilepticus: Is More Always Better?

BACKGROUND AND OBJECTIVES: Benzodiazepines are the first treatment line in status epilepticus (SE). Despite their well-established benefit, benzodiazepines are frequently underdosed with potential detrimental consequences. In some European countries, clonazepam (CLZ) is commonly used as the first line treatment. The aim of this study was to explore the correlation between CLZ loading doses and SE outcome. METHODS: This study included a retrospective analysis of a prospective registry in Lausanne, Switzerland (CHUV Lausanne University Hospital), including all SE episodes treated between February 2016 and February 2021. Only adults (> 16 years old) were included with CLZ used as the first treatment line. Post-anoxic SE were excluded because of significant differences in physiopathology and prognosis. Patient characteristics, SE features, the validated SE severity score (STESS), and treatment characteristics were prospectively recorded. We considered loading doses of 0.015 mg/kg or higher (following commonly recommended loading doses) as high doses. We analyzed outcome in terms of number of treatment lines after the CLZ, proportion of refractory episodes, intubation for airways protection, intubation for SE treatment, and mortality. We performed univariable analyses to investigate the association between loading doses and clinical response. A multivariable stepwise backward binary logistic regression was applied for adjusting for potential confounders. Multivariable linear regression was similarly used to analyze CLZ dose as a continuous variable. RESULTS: We collected 251 SE episodes in 225 adult patients. Median CLZ loading dose was 0.010 mg/kg. CLZ high doses were used in 21.9% of SE episodes (in 43.8% for > 80% of the high dose). Thirteen percent of patients with SE were intubated for airways control, while intubation was needed in 12.7% for SE treatment. High CLZ loading doses were independently associated with younger age (median 62 versus 68 years old, p = 0.002), lesser weight (65 kg versus 75 kg, p = 0.001) and more frequent intubation for airways protection (23% vs 11%, p = 0.013), but differing CLZ dose was not associated with any outcome parameter. CONCLUSION: CLZ high doses were more frequently used for SE treatment in younger patients with healthy weight and were more often associated with intubation for airways protection, probably as an adverse event. Varying CLZ dose did not alter outcome in SE, raising the possibility that commonly recommended doses are above what is needed, at least in some patients. Our results suggest that CLZ doses in SE may be individualized depending on the clinical setting.

Relationship between serum neuron-specific enolase and EEG after cardiac arrest: A reappraisal.

OBJECTIVE: Electroencephalogram (EEG) and serum neuron specific enolase (NSE) are frequently used prognosticators after cardiac arrest (CA). This study explored the association between NSE and EEG, considering the role of EEG timing, its background continuity, reactivity, occurrence of epileptiform discharges, and pre-defined malignancy degree. METHODS: Retrospective analysis including 445 consecutive adults from a prospective registry, surviving the first 24 hours after CA and undergoing multimodal evaluation. EEG were interpreted blinded to NSE results. RESULTS: Higher NSE was associated with poor EEG prognosticators, such as increasing malignancy, repetitive epileptiform discharges and lack of background reactivity, independently of EEG timing (including sedation and temperature). When stratified for background continuity, NSE was higher with repetitive epileptiform discharges, except in the case of suppressed EEGs. This relationship showed some variation according to the recording time. CONCLUSIONS: Neuronal injury after CA, reflected by NSE, correlates with several EEG features: increasing EEG malignancy, lack of background reactivity, and presence of repetitive epileptiform discharges. The correlation between epileptiform discharges and NSE is influenced by underlying EEG background and timing. SIGNIFICANCE: This study, describing the complex interplay between serum NSE and epileptiform features, suggests that epileptiform discharges reflect neuronal injury particularly in non-suppressed EEG.

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.

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.

Resilience and its correlates in patients with narcolepsy type 1.

STUDY OBJECTIVES: This study aimed to explore resilience and its possible association with sociodemographic and clinical features in patients with narcolepsy type 1 (NT1). METHODS: This was a cross-sectional study involving patients with NT1 and age-/sex-matched controls (comparison group). Sociodemographic and clinical data were collected through semistructured interviews and validated questionnaires, including the Epworth Sleepiness Scale (ESS), State-Trait Anxiety Inventory (STAI)-State Anxiety, Beck Depression Inventory (BDI), 36-item Short Form Survey (SF-36), and the Resilience Scale (RS). Different statistical approaches were used to investigate the relationship between resilience and NT1 and associations with sociodemographic and clinical features. RESULTS: The participants comprised 137 patients (mean age, 38.0 years; 52.6% female) and 149 controls (39.6 years; 55.7% female). Compared with controls, patients had a significantly lower (122.6 vs 135.5) mean RS score and a 2-fold risk of having low/mild-range resilience (adjusted odds ratio = 1.99, 95% confidence interval 1.13-3.52). Patients with high resilience had sociodemographic and narcolepsy characteristics similar to patients with low resilience, but they reported anxiety and depressive symptomatology less frequently (4.2% vs 55.8% and 58.3%, respectively), and their SF-36 scores were comparable to those of the comparison group. In patients, RS score was strongly associated with STAI-State Anxiety and BDI (rho = -0.57 and -0.56, respectively) and weakly with ESS (rho = -20) scores. CONCLUSIONS: The results of this study suggest that resilience may play a key role in patients' adaptation to NT1. Furthermore, this study supports interventions aimed at increasing patients' resilience and provides a base for further studies, preferably longitudinal and including objective measures, directed toward understanding the relationship between resilience, depression, and quality of life in patients with narcolepsy. CITATION: D'Alterio A, Menchetti M, Zenesini C, et al. Resilience and its correlates in patients with narcolepsy type 1. J Clin Sleep Med. 2023;19(4):719-726.

[Neurology: what's new in 2022]. / Neurologie : ce qui a changé en 2022.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies.

L'année 2022 a été marquée par l'arrivée de nombreux traitements pour la myasthénie réfractaire. Le lien entre l'épilepsie et le risque cérébro-vasculaire a été bien étudié, démontrant que la lamotrigine semble être le meilleur traitement pour prévenir la mortalité chez les patients de 45 ans et plus. De nouvelles études ont enfin pu établir l'utilité de la thrombectomie dans les occlusions basilaires. Le lien entre le virus d'Epstein-Barr et la sclérose en plaques a pu être prouvé à la suite d'une importante étude de cohorte. Une nouvelle technique d'administration sous-cutanée de la lévodopa semble prometteuse. Enfin, de nombreuses études confirment l'efficacité et l'excellente tolérance des anticorps anti-CGRP (Calcitonine Gene Related Protein).

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.

Benign EEG for prognostication of favorable outcome after cardiac arrest: A reappraisal.

AIM: The current EEG role for prognostication after cardiac arrest (CA) essentially aims at reliably identifying patients with poor prognosis ("highly malignant" patterns, defined by Westhall et al. in 2014). Conversely, "benign EEGs", defined by the absence of elements of "highly malignant" and "malignant" categories, has limited sensitivity in detecting good prognosis. We postulate that a less stringent "benign EEG" definition would improve sensitivity to detect patients with favorable outcomes. METHODS: Retrospectively assessing our registry of unconscious adults after CA (1.2018-8.2021), we scored EEGs within 72 h after CA using a modified "benign EEG" classification (allowing discontinuity, low-voltage, or reversed anterio-posterior amplitude development), versus Westhall's "benign EEG" classification (not allowing the former items). We compared predictive performances towards good outcome (Cerebral Performance Category 1-2 at 3 months), using 2x2 tables (and binomial 95% confidence intervals) and proportions comparisons. RESULTS: Among 381 patients (mean age 61.9 ± 15.4 years, 104 (27.2%) females, 240 (62.9%) having cardiac origin), the modified "benign EEG" definition identified a higher number of patients with potential good outcome (252, 66%, vs 163, 43%). Sensitivity of the modified EEG definition was 0.97 (95% CI: 0.92-0.97) vs 0.71 (95% CI: 0.62-0.78) (p < 0.001). Positive predictive values (PPV) were 0.53 (95% CI: 0.46-0.59) versus 0.59 (95% CI: 0.51-0.67; p = 0.17). Similar statistics were observed at definite recording times, and for survivors. DISCUSSION: The modified "benign EEG" classification demonstrated a markedly higher sensitivity towards favorable outcome, with minor impact on PPV. Adaptation of "benign EEG" criteria may improve efficient identification of patients who may reach a good outcome.

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.