INTRODUCTION:Transcranial direct current stimulation (tDCS) has shown encouraging results in patients with Disorders of Consciousness (DoC), yet its efficacy and mechanisms remain unclear. This study aimed to evaluate the effects of left dorsolateral prefrontal cortex (DLPFC) tDCS on Coma Recovery Scale-Revised (CRS-R) scores and EEG activity in severely brain-injured DoC patients. METHODS:In a double-blind, sham-controlled crossover design, 2 mA anodal and sham tDCS were randomly administered over the left DLPFC (right orbito-frontal cathode) for 20 min. CRS-R scores, event-related potentials using the local-global paradigm and resting EEG were recorded before and after each stimulation. Follow-up assessments occurred at 6 weeks and 6 months. RESULTS:Between November 2018 and April 2022, 20 patients were included (12 in a Minimally Conscious State (MCS), 7 in a Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS), and one patient who emerged from MCS (emergence from MCS (eMCS)). Group-level analysis across all patients revealed a significant treatment effect on CRS-R scores (p = 0.02). Nine patients (45%; 6 MCS, 3 VS/UWS) responded to tDCS, with five (25%; 3 MCS, 2 VS/UWS) exhibiting new behavioural items absent in pre- and post-sham evaluations. However, no patient demonstrated a change in consciousness state (e.g., transition from VS/UWS to MCS), nor was any improvement observed at 6-week or 6-month. EEG analysis showed increased complexity, gamma-band power, and delta-band cortico-cortical functional connectivity post-tDCS. Multivariate EEG analyses did not show a significant effect of tDCS on the prediction of conscious state, and ERP assessments using the local-global paradigm revealed no modulation of novelty detection responses following stimulation. Simulation analyses on individual brain anatomical structures revealed that responders displayed stronger tDCS-induced electric fields within a Fronto-parietal network than non-responders. CONCLUSION:Despite the limited sample size, our results provide additional evidence in favour of the behavioural and electrophysiological effects of tDCS in DoC patients.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent complication of CD19 CAR T-cell therapy. Although several biomarkers, particularly S100β, have been reported to be associated with ICANS, their biological significance and specificity remain unclear. We retrospectively studied adult patients treated with commercial CD19 CAR T cells between 2020 and 2024, focusing on early serum dynamics of S100β and neuron-specific enolase (NSE). Among 122 treated patients, 72 had complete paired biomarker measurements and were included; 21 (29

Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation—functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals that specific modalities, such as functional assessments, provide comprehensive insights into the currently evaluated state of consciousness, the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centres with different acquisition parameters. Importantly, we demonstrate that model performance improves with an increase in the number of modalities. We observe a higher inter-modality disagreement for minimally conscious state patients and those patients who improve. Lastly, we observe a difference in feature importances between diagnosis and prognosis, with an interaction between modality and anatomical structures: some subcortical markers tend to contribute more to prognosis, while other cortical markers are more informative for diagnosis. This integrative multimodal and machine learning methodology presents a promising avenue for a more nuanced understanding of disorders of consciousness, contributing to enhanced diagnostic precision, prognostic capabilities and the personalization of rehabilitative strategies in clinical practice.

Different commentators are often invited in the media in order to discuss medical and health-related advances, such as the deployment of new vaccines or prevention tests. How do the expertise and opinions of such intermediaries affect public trust towards them? Do these factors also influence the public beliefs and decisions regarding those medical advances? We presented to 1984 French participants new (fictitious) medical tools that have been recently made available and commented on by individuals of different degrees of expertise and having distinct opinions. The results indicate that both factors significantly influenced participants' trust in the commentator's message. The commentator's opinion also affected (although to a smaller extent) the public attitude towards the tool and their willingness to use it. Crucially, participants recognized that commentators' assertiveness in expressing their opinions might unduly bias their beliefs. The study highlights the importance of considering both para-verbal and contextual cues in health communication, advocating for strategies to mitigate (or better use) their influence on public trust, beliefs, and decision-making.

A reliable outcome prognostication tool for patients in coma of various etiologies would facilitate ICU treatment by providing objective information to caregivers and patients' relatives. This study aimed to predict outcome based on supervised machine learning and magnetic resonance diffusion tensor imaging (DTI) metrics. In this multicenter international study, a training set of 531 patients not responding to simple orders at day 5 after coma onset underwent diffusion-weighted MRI between day 5 and 45. A classifier was developed using DTI metrics, patient age, and delay between admission and MRI as features. Unfavorable outcome (UFO) was defined as GOSE 1–4 at one year. Three prognosis areas were defined: a “red” zone (specificity for UFO above 95

BACKGROUND:Anti-N-methyl D-aspartate-receptor encephalitis (anti-NMDARe) is a severe disease with a favorable outcome when immunomodulatory management is started rapidly. The main objective of this study is to compare the early efficacy of the two most frequently used therapeutics, i.e., intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE), in intensive care patients admitted for anti-NMDARe. METHODS:This is an observational retrospective study of patients hospitalized in a tertiary medical neurointensive care unit for severe anti-NMDARe. Patients were categorized according to the modality of first-line immunomodulatory therapies associated with corticosteroids: TPE, IVIG, or IVIG followed by TPE. The primary end point was the effectiveness of the first-line immunomodulatory treatment. Treatment was considered effective when no other immunomodulatory therapy was introduced and the patient met the following three conditions: response to simple commands, absence of epileptic seizures, and absence of abnormal movements. RESULTS:Thirty-seven patients were included in the study from January 2007 to December 2022: 8 were treated with TPE alone, 13 were treated with IVIG alone, and 16 were treated with IVIG followed by TPE. Of the 29 patients treated with IVIG, 13 showed improvement, with a median latency to treatment response of 36 days, whereas 16 were switched to TPE, with a median latency to treatment response of 30 days due to a lack of improvement. All eight patients treated with TPE improved, with a latency to treatment response of 31 days. TPE was significantly more effective than IVIG. CONCLUSIONS:This study raises the hypothesis that immunotherapies may have differential response rates among patients with NMDARe. Although the retrospective nature of the analysis may be subject to bias and confounding, the potential for therapeutic impact deserves prospective evaluation.

Guillain-Barré Syndrome (GBS) is a leading cause of acute flaccid tetraplegia worldwide, with an incidence of 1–2 cases per 100,000 people per year. Characterized by an immune-mediated polyneuropathy, GBS often follows infections or immunological triggers, including vaccinations. The syndrome is classified into three main subtypes based on electrophysiological findings: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN). The pathophysiology of GBS involves molecular mimicry between microbial antigens and nerve structures, particularly affecting gangliosides and myelin proteins. Diagnosis primarily relies on clinical history, with lumbar puncture and electroneuromyogram used to confirm and differentiate subtypes. Treatment includes intravenous immunoglobulins or therapeutic plasma exchange associated with symptomatic treatment, especially mechanical ventilation if needed. Prognosis is generally favorable with a low mortality rate (< 5

Understanding the neural mechanisms underlying disorders of consciousness (DoC) remains a major challenge, particularly in distinguishing limited awareness in minimally conscious state (MCS) and complete unawareness in unresponsive wakefulness syndrome, also coined vegetative state (UWS/VS). In this multicentre study, we fitted a biophysically informed corticothalamic neural field model to high-density EEG data from two large independent datasets, comprising 203 UWS patients, 270 MCS patients and 74 healthy controls. We then used the fitted parameters to simulate EEG time series on a per-subject basis and compared empirical and simulated complexity metrics. The model reliably captured the spectral features across different states of consciousness and revealed reduced corticothalamic integrity in DoC patients that was more pronounced in UWS than in MCS, supporting the mesocircuit hypothesis. Furthermore, the simulated EEG reproduced the complexity patterns of the empirical recordings, with permutation entropy emerging as a sensitive marker capable of distinguishing between MCS and UWS for both real and simulated time series. ### Competing Interest Statement The authors have declared no competing interest. University and University Hospital of Liège Belgian National Funds for Scientific Research (FRS-FNRS) FNRS PDR project, T.0134.21 FNRS MIS project, F.4521.23 FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project) program Investissements d'avenir ANR-10-IAIHU-06 JTC the fund Generet King Baudouin Foundation BIAL Foundation Mind Science Foundation European Commission Fondation Leon Fredericq Mind-Care foundation National Natural Science Foundation of China, 81471100 European Foundation of Biomedical Research FERB Onlus Horizon 2020 MSCA - Research and Innovation Staff Exchange DoC-Box project, HORIZON-MSCA-2022-SE-01-01; 101131344 FWO, 1265522N

Disorders of consciousness (DoC) represent a spectrum of clinical conditions, including coma, unresponsive wakefulness syndrome, and the minimally conscious state, which may result from structural and non-structural brain injuries due to trauma, stroke, anoxia, infections of the brain, and other causes. Clinical management of patients with DoC is especially challenging in the critical care environment, where the level of consciousness, a key factor in determining the trajectory of recovery, may be obscured by sedation, analgesia, and other confounders. The 2025 International Symposium on Intensive Care and Emergency Medicine hosted a Roundtable of 18 expert clinicians and researchers to synthesise and discuss the latest evidence on acute DoC epidemiology, diagnosis, treatment, and prognosis. Here, we summarise the output of the Roundtable in the format of a roadmap with six steps related to identifying patients with DoC, assessing for and treating confounders, establishing a diagnosis and prognosis, selecting interventions, and effectively communicating with family. This roadmap provides practical, evidence-informed guidance to help intensivists navigate diagnosis, treatment, and prognostication in patients with acute DoC. Advances in structural and functional neuroimaging, electrophysiology, and blood-based biomarkers offer promise for refined diagnostics and prognostication, though their clinical translation remains limited.

Background and objectives – Absent cough reflex is associated with mortality intensive care unit (ICU) patients requiring deep sedation, suggesting that lower brainstem dysfunction contributed to adverse outcomes. We conducted a multicenter observational cohort study to confirm this hypothesis by assessing the peak latency (PL) of the lower brainstem-generated P14 evoked potential (EP), which is slightly increased by sedatives. We aimed to demonstrate that a P14-PL> 16 ms is independently associated with day-28 mortality. Patients and methods - Mechanically ventilated adult patients, comatose or deeply sedated, brain-injured or not, were included. At day 3, EPs were performed in patients remaining unconscious. The Simplified Acute Physiological Score (SAPSII), initial Glasgow Coma Scale (GCS), sedation depth and brainstem reflexes were collected. The primary outcome was 28-day mortality. The secondary outcomes were delayed awakening and delirium after sedation discontinuation. Results - Between 2015 and 2019, 322 patients were included. EPs were performed in 264 (82%) patients, including 140 (53%) brain-injured and 251 (95%) deeply sedated patients. The median age, SAPSII and initial GCS were 62 years [50; 71], 49 [40; 62] and 11 [6; 15], respectively. A P14-PL > 16ms was found in 76 (29%) patients and was associated with day-28 mortality (adjusted hazard ratio, 3.0; 95% confidence interval, [1.7-5.2]). Absent cough and pupillary light reflexes were associated with death. Only absent oculocephalogyre reflex was associated with delayed awakening (adjusted odds ratio, 2.1, 95%CI, [1.1 - 3.7]). Interpretation – Impaired neurological and neurophysiological lower brainstem responses are associated with mortality in deeply sedated patients. Funded by the French Ministry of Health; PRORETRO; n° P120915; ClinicalTrials.gov registry: NCT02395861; date: 24 March 2015

Retinal illumination primarily determines pupil size, yet extra-retinal factors like subjective brightness also influence pupillary responses. Previous works reported that in healthy individuals, stimuli whose semantic content evokes brightness cause greater pupillary constriction than control stimuli of similar luminance. This study adapted this approach and tested a passive task to assess consciousness levels of non-communicating patients in intensive care unit. In ten healthy participants and seventeen patients with Disorders of Consciousness (10 in a Minimally Conscious State, 6 in Vegetative State also coined Unresponsive Wakefulness Syndrome), 1 in Emergence from Minimally Conscious State), we measured pupillary responses to photographs of the sun and control stimuli of matched luminance (moon photographs, scrambled sun images, uniform gray squares). At the group level, both healthy participants and Minimally Conscious State patients showed greater pupil constriction for the sun photographs compared to control pictures which elicited a pupillary dilatation. In Vegetative State/ Unresponsive Wakefulness Syndrome patients, this subjective brightness effect on pupillary diameter was not significant. Notably, this effect was observed in only one Vegetative State patient, who regained consciousness a few weeks after the evaluation. The results support that pupillary response to subjective brightness could be a novel method to assess residual cognition at the bedside in non-communicating patients.

As a response to the environment and internal signals, brain networks reorganize on a sub-second scale. To capture this reorganization in patients with disorders of consciousness (DoC) and understand their residual brain activity, we investigated the dynamics of electroencephalography (EEG) microstates. EEG microstates are meta-stable topographies that last tens to a few hundreds of milliseconds and are hypothesized to reflect large-scale cortical networks. To obtain EEG‑microstate segmentation, EEG topographies per sample were clustered into four groups for the purpose of the present comparison with the existing four‑class literature. We then obtained a time series of maps with different frequencies of occurrence and duration. One such occurrence of a map with a given duration is called a microstate. The goal of this work was to study the static and dynamic properties of these topographical patterns in DoC patients. Using the microstate time series, we calculated static and dynamic markers. In contrast to the static, the dynamic metrics depend on the specific temporal sequences of the maps. The static measure map coverage showed differences between healthy controls and patients. In contrast, some dynamic markers captured inter-patient group differences. The dynamic markers we investigated are Mean Microstate Durations (MMD), Microstate Duration Variances (MDV), Microstate Transition Matrices (MTM), and Entropy Production (EP). The MMD and MDV decreased with the state of consciousness, whereas the MTM non-diagonal transitions and EP increased. In other words, DoC patients had slower and closer to equilibrium (time-reversible) brain dynamics. In conclusion, static and dynamic EEG microstate metrics differed across consciousness levels, with the latter having captured the subtler differences between groups of patients with DoC.

INTRODUCTION:Acute encephalopathy in the ICU poses significant diagnostic, therapeutic, and prognostic challenges. Standardized expert guidelines on acute encephalopathy are needed to improve diagnostic methods, therapeutic decisions, and prognostication. METHODS:The experts conducted a review of the literature, analysed it according to the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) methodology and made proposals for guidelines, which were rated by other experts. Only expert opinions with strong agreement were selected. RESULTS:The synthesis of expert work and the application of the GRADE method resulted in 39 recommendations. Among the 39 formalized recommendations, 1 had a high level of evidence (GRADE 1 +) and 10 had a low level of evidence (GRADE 2 + or 2-). These recommendations describe indication for ICU admission, use of clinical scores and EEG for diagnosis, detection of complications, and prognostication. The remaining 28 recommendations were based on expert consensus. These recomandations describe common indications for blood and CSF studies, neuroimaging, use of neuromonitoring, and provide guidelines for management in the acute phase. CONCLUSION:This expert consensus statement aims to provide a structured framework to enhance the consistency and quality of care for ICU patients presenting with acute encephalopathy. By integrating high-quality evidence with expert opinion, it offers a pragmatic approach to addressing the complex nature of acute encephalopathy in the ICU, promoting best practices in patient care and facilitating future research in the field.

BACKGROUND:Central nervous system autoimmune diseases (CNS-AD) such as autoimmune encephalitis and myelitis are severe conditions, often requiring ICU admission. Early diagnosis is crucial but difficult, as initial steps facing sub-acute neurological disorders try to exclude non-immune causes such as stroke or infections through MRI and multiplex PCR assays. Current acute-phase autoimmune identifiers are lacking, with definitive diagnosis hinging on delayed tests like antibody detection or intrathecal immunoglobulin synthesis (ISI) identification via iso-electric focalization (IEF). This study evaluates surrogate markers, such as the IgG quotient (QIgG), IgG index, and Reiber's formula, which are rapidly obtainable, to quickly predict ISI in the ICU setting, aiming to expedite treatment initiation. METHODS:We screened all neuro-ICU admissions from 2008 to 2022 in our center, including patients who underwent a lumbar puncture (LP) and were tested for ISI via IEF. We excluded those lacking concomitant CSF/serum albumin and IgG data. Patients were categorized by final diagnosis as "CNS-AD" or "other", and whether ISI was present. We calculated QIgG, IgG index, and Reiber's formula, comparing their performance to IEF for sensitivity (Se) and specificity (Sp). RESULTS:ISI was detected in 35% of patients (93/266). In the "CNS-AD" group, 54% were ISI-positive, while 21% of patients in the "Other" group also showed ISI. Among the three indexes, only the IgG index showed strong specificity (95%) but moderate sensitivity (56%). QIgG and Reiber's formula had similar sensitivity (67% and 66%) but lower specificity (41% for both). Multivariable analysis identified age < 50 years (OR 2.5 [95% CI 1.3-4.7]) and an IgG index > 0.7 (OR 14.2 [95% CI 6.6-32.0]) as factors independently associated with ISI positivity. Using the Youden index and likelihood ratio, we recalibrated thresholds to improve performance. A "grey zone" was defined for the IgG index (0.67-0.80), below which ISI was unlikely and above which it was considered probable. CONCLUSION:While the IgG index's low sensitivity limits its standalone diagnostic use, its high specificity makes this index a good one when positive, to weigh in the decision-making process to treat or not a patient with suspected CNS-AD, while awaiting IEF results, which can take days or even weeks in some centers.

Objectives:The aim of this study was to evaluate the contribution of metagenomic next-generation sequencing (mNGS) in critically ill patients with encephalitis of unknown etiology. Methods:This retrospective study (2016-2023) was conducted in a tertiary care referral neuro-ICU at La Pitié-Salpêtrière Hospital (Paris, France). The inclusion criteria were encephalitis with unknown etiology and mNGS performed on CSF, brain biopsy, and/or autopsy. We assessed the yield of mNGS and whether specific treatments were initiated. Neurologic outcome at 1 year was assessed using the Glasgow Outcome Scale-Extended (GOSE-1: death; GOSE-8: upper good recovery). Results:A total of 49 patients were included, of whom 44.9% were immunosuppressed. At 1 year, 38.8% had a GOSE score 4-8 and 47.7% died. mNGS was performed on the CSF of 40 of 49 patients (81.6%) and on brain biopsy of 19 of 49 patients (38.8%), including 12 patients who underwent both CSF and biopsy testing. Among the 40 mNGS analyses performed on the CSF, 7 (17.5%) yielded positive results but only 1 (2.5%) was likely causative. Conversely, 7 of 19 mNGS analyses (36.8%) on biopsies were positive and causative. Regarding the yield of mNGS in the entire cohort, 15 of 49 patients (30.6%) had a positive result but only 7 of 49 (14.3%) were causative (dengue virus, measles virus, rubella virus, Nocardia spp, HHV6, astrovirus, and orthobunyavirus), all from brain biopsies of immunocompromised patients. Conversely, 8 of 49 mNGS analyses (16.3%) were noncausative (polyomavirus, HHV8, HHV7, EBV, 2 pegiviruses, and 2 rhinoviruses). Specific treatments were initiated in 4 of 7 patients (57%). Among the 34 patients with a negative mNGS result, 5 (14.7%) were diagnosed with infectious encephalitis using conventional methods. Conclusion:In critically ill patients with encephalitis of unknown etiology, mNGS performed on brain biopsy could reduce diagnostic uncertainty.

Myasthenic crisis often requires prolonged mechanical ventilation and complex weaning, yet data remain scarce. The objective of this study was to describe the weaning characteristics in patients with myasthenic crisis using the WEAN Safe classification. Secondary aims included assessment of long-term outcome and comparison between early- and late-onset (< 65 years) versus very-late-onset MG (≥ 65 years) myasthenia gravis. This single-center retrospective study included patients admitted for myasthenic crisis to a tertiary neuro–intensive care unit between January 2008 and December 2023. Clinical characteristics, ventilatory support parameters, timing of weaning events, complications, and outcomes were recorded. Weaning was classified according to WEAN Safe definitions: no separation attempt, short wean (successful weaning within 1 day), intermediate wean (2–6 days), prolonged wean (≥ 7 days), or failed wean (persistent invasive ventilation at discharge or death). Among 698 ICU hospitalizations (405 patients) for myasthenia gravis, 131 (120 patients) received invasive mechanical ventilation. Fifty hospitalizations (39 patients) were excluded due to non-MC-related intubation, insufficient weaning data or patients with multiple ICU admissions. The final analysis included 81 patients (median age 70 years [54–81]; 43

Absent cough reflex is associated with mortality in intensive care unit (ICU) patients requiring deep sedation, suggesting that lower brainstem dysfunction contributes to adverse outcomes. We conducted a multicenter observational cohort study to confirm this hypothesis by assessing the peak latency (PL) of the lower brainstem-generated P14 evoked potential (EP), which is slightly increased by sedatives. We aimed to demonstrate that a P14-PL > 16 ms is independently associated with day-28 mortality. Mechanically ventilated adult patients, comatose or deeply sedated, brain injured or not, were included. At day 3, EPs were performed in patients remaining unconscious. The Simplified Acute Physiological Score (SAPSII), initial Glasgow Coma Scale (GCS), sedation depth, and brainstem reflexes were collected. The primary outcome was day-28 mortality. The secondary outcomes were delayed awakening and delirium after sedation discontinuation. Between 2015 and 2019, 322 patients were included. EPs were performed in 264 (82