INTRODUCTION/AIMS:Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease (FEWDON-MND) is characterized by motor weakness predominantly affecting finger extension, accompanied by downbeat nystagmus. To date, only 11 patients have been reported. The present study adds a further three and aims to provide a more detailed description of the electrodiagnostic features of these patients. METHODS:We present the clinical and electrophysiological features of three French patients from specialized motor neuron centers and review the electrophysiological findings of previously reported patients. RESULTS:These three patients presented with pure motor weakness affecting finger extension and downbeat nystagmus. They exhibited a slowly progressive disease course without respiratory involvement. Nerve conduction studies showed decreased compound muscle action potential amplitudes in the extensor indicis muscles. Abnormal spontaneous activity on needle electromyography (EMG) was rare in two patients, absent in one, and otherwise limited to weak muscles. Additionally, chronic motor axon loss features suggestive of motor neuronopathy were seen in our patients. Importantly, they were also detected in distant asymptomatic muscles. DISCUSSION:The three patients reported here confirm the typical phenotype of FEWDON-MND, characterized by slowly progressive distal motor weakness initially affecting finger extension, associated with downbeat nystagmus. Although chronic motor axon loss features have been found in all reported patients, our three patients show that active denervation can be absent or rare. Thus, finger drop and diffuse chronic neurogenic changes on EMG should lead clinicians to look for downbeat nystagmus and to consider FEWDON-MND.

Brain connectivity, allowing information to be shared between distinct cortical areas and thus to be processed in an integrated way, has long been considered critical for consciousness. However, the relationship between functional intercortical interactions and the structural connections thought to underlie them is poorly understood. In the present work, we explore both functional (with an EEG-based metric: the median weighted symbolic mutual information in the theta band) and structural (with a brain MRI-based metric: fractional anisotropy) connectivities in a cohort of 78 patients with disorders of consciousness. Both metrics could distinguish patients in a vegetative state from patients in minimally conscious state. Crucially, we discovered a significant positive correlation between functional and structural connectivities. Furthermore, we showed that this structure-function relationship is more specifically observed when considering structural connectivity within the intra- and inter-hemispheric long-distance cortico-cortical bundles involved in the Global Neuronal Workspace (GNW) theory of consciousness, thus supporting predictions of this model. Altogether, these results support the interest of multimodal assessments of brain connectivity in refining the diagnostic evaluation of patients with disorders of consciousness.

Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness (DoC). This spectrum includes clinical categories such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioral assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to look for 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 assessment through interpretable machine learning (ML). The electrophysiological modalities included high-density electroencephalography (EEG) (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional magnetic resonance imaging (MRI), diffusion MRI, and 18F-fluoro-deoxy-glucose positron emission tomography (FDG 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 centers with different acquisition parameters. Importantly, we show that there is an improved model performance with the increase in the number of modalities. We observe a higher inter-modality disagreement for MCS patients and those patients who improve. Lastly, we observe a difference in feature importances in diagnosis and prognosis. This integrative multimodal and ML methodology presents a promising avenue for a more nuanced understanding of DoC, contributing to enhanced diagnostic precision and prognostic capabilities in clinical practice. ### Competing Interest Statement Jacobo D. Sitt and Lionel Naccache are scientific co-founders of NeuroMeters (have scientific advisory activity but no executive or management activity). ### Funding Statement This work was supported by the Ecole Doctorale Frontieres de l'Innovation en Recherche et Education-Programme Bettencourt (to D.M.). This project is part of the multicentric application for the EU ERAPerMed Joint Translational Call for Proposals for "Personalised Medicine: Multidisciplinary research towards implementation" (ERA PerMed JTC2019). It is funded by local funding agencies of the participating countries (for France it is the Agence Nationale de Recherche ANR, funding code: ANR-19-PERM-0002, for Germany the Federal Ministry of Education and Research BMBF, funding code: 01KU2003). This project is supported by the Human Brain Project (HBP) MODELDxConsciousness Consortium (Agence Nationale de Recherche ANR, funding code: S.1600.ANR.HBPR). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Pitie-Salpetriere Hospital (Comite de Protection des Personnes, Ile de France 1, Paris, France) under the French label of routine care research (protocol number 2013-A01385-40, code Recherche en soins courants, protocol number M-Neuro-DOC, CE SRLF 20-2). Medical Faculty of Ludwig-Maximilians-Universitat Munchen (Germany) (protocol numbers 20-634 and 20-635). IRCCS Fondazione Don Carlo Gnocchi (IRCCS Regione Lombardia, Italy) (protocol number 32/2021/CE_FdG/FC/SA). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data is not publicly available.

Probing cognition and consciousness in the absence of functional communication remains an extremely challenging task. In this perspective, we imagined a basic clinical procedure to explore pain anticipation at bedside. In a series of 61 patients with a disorder of consciousness, we tested the existence of a nociceptive anticipation response by pairing a somaesthetic stimulation with a noxious stimulation. We then explored how nociceptive anticipation response correlated with (i) clinical status inferred from Coma Recovery Scale-Revised scoring, (ii) with an EEG signature of stimulus anticipation-the contingent negative variation-and (iii) how nociceptive anticipation response could predict consciousness outcome at 6 months. Proportion of nociceptive anticipation response differed significantly according to the state of consciousness: nociceptive anticipation response was present in 5 of 5 emerging from minimally conscious state patients (100%), in 10 of 11 minimally conscious state plus patients (91%), but only in 8 of 17 minimally conscious state minus patients (47%), and only in 1 of 24 vegetative state/unresponsive wakefulness syndrome patients (4%) (chi(2 ) P < 0.0001). Nociceptive anticipation response correlated with the presence of a contingent negative variation, suggesting that patients with nociceptive anticipation response were more prone to actively expect and anticipate auditory stimuli (Fisher's exact test P = 0.05). However, nociceptive anticipation response presence did not predict consciousness recovery. Nociceptive anticipation response appears as a new additional behavioural sign that can be used to differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome patients. As most behavioural signs of minimally conscious state, the nociceptive anticipation response seems to reveal the existence of a cortically mediated state that does not necessarily reflect residual conscious processing.

Background: Although the group of paroxysmal kinesigenic dyskinesia (PKD) genes is expanding, the molecular cause remains elusive in more than 50% of cases. Objective: The aim is to identify the missing genetic causes of PKD. Methods: Phenotypic characterization, whole exome sequencing and association test were performed among 53 PKD cases. Results: We identified four causative variants in KCNJ10, already associated with EAST syndrome (epilepsy, cerebellar ataxia, sensorineural hearing impairment and renal tubulopathy). Homozygous p.(Ile209Thr) variant was found in two brothers from a single autosomal recessive PKD family, whereas heterozygous p.(Cys294Tyr) and p.(Thr178Ile) variants were found in six patients from two autosomal dominant PKD families. Heterozygous p.(Arg180His) variant was identified in one additional sporadic PKD case. Compared to the Genome Aggregation Database v2.1.1, our PKD cohort was significantly enriched in both rare heterozygous (odds ratio, 21.6; P = 9.7 x 10(-8)) and rare homozygous (odds ratio, 2047; P = 1.65 x 10(-6)) missense variants in KCNJ10. Conclusions: We demonstrated that both rare monoallelic and biallelic missense variants in KCNJ10 are associated with PKD. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

ObjectivesParoxysmal ataxia is typically characterized by early-onset attacks of cerebellar ataxia. Late-onset cerebellar ataxia (LOCA) comprises a group of neurodegenerative disorders mainly characterized by adult-onset progressive cerebellar ataxia. A deep intronic expansion of a GAA triplet in the FGF14 gene encoding fibroblast growth factor 14 has recently been identified as a frequent cause of LOCA.MethodsWe describe a patient with paroxysmal ataxia/dysarthria due to a FGF14 repeat expansion and 3 affected family members.ResultsThe 4 patients had paroxysmal ataxia/dysarthria occurring between 45 and 50 years as the initial manifestation of a FGF14 repeat expansion. The index case was investigated in detail. We have provided a video showing one of her paroxysmal episodes that could be triggered by alcohol, coffee, exertion, emotion, or cigarette smoking. Brain MRI revealed mild cerebellar atrophy, and oculography showed a subclinical downbeat nystagmus. Treatment with acetazolamide resulted in remarkable improvement.DiscussionParoxysmal dysarthria/ataxia should prompt the clinician to test for FGF14 repeat expansion/SCA27B, especially when the paroxysmal attacks are associated with late-onset cerebellar ataxia and/or a family history consistent with a dominant disorder.

ObjectiveAccording to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC).MethodsWe provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved.ResultsVisual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC.InterpretationThese results are consistent with the hypothesis of a causal role of PFC in visual awareness.

BACKGROUND:SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability. METHODS:We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor. FINDINGS:A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA250-299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAA≥300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (-15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees. INTERPRETATION:SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling. FUNDING:This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux - France (to GS) and by the European Union's Horizon 2020 research and innovation program under grant agreement No 779257 ("SOLVE-RD" to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL.

Pupil dilation response (PDR) has been proposed as a physiological marker of conscious access to a stimulus or its attributes, such as novelty. In a previous study on healthy volunteers, we adapted the auditory “local global” paradigm and showed that violations of global regularity elicited a PDR. Notably without instructions, this global effect was present only in participants who could consciously report violations of global regularities. In the present study, we used a similar approach in 24 non-communicating patients affected with a Disorder of Consciousness (DoC) and compared PDR to ERPs regarding diagnostic and prognostic performance. At the group level, global effect could not be detected in DoC patients. At the individual level, the only patient with a PDR global effect was in a MCS and recovered consciousness at 6 months. Contrasting the most regular trials to the most irregular ones improved PDR’s diagnostic and prognostic power in DoC patients. Pupillometry is a promising tool but requires several methodological improvements to enhance the signal-to-noise ratio and make it more robust for probing consciousness and cognition in DoC patients.

Objectives:Paroxysmal ataxia is typically characterized by early-onset attacks of cerebellar ataxia. Late-onset cerebellar ataxia (LOCA) comprises a group of neurodegenerative disorders mainly characterized by adult-onset progressive cerebellar ataxia. A deep intronic expansion of a GAA triplet in the FGF14 gene encoding fibroblast growth factor 14 has recently been identified as a frequent cause of LOCA.Methods:We describe a patient with paroxysmal ataxia/dysarthria due to a FGF14 repeat expansion and 3 affected family members.Results:The 4 patients had paroxysmal ataxia/dysarthria occurring between 45 and 50 years as the initial manifestation of a FGF14 repeat expansion. The index case was investigated in detail. We have provided a video showing one of her paroxysmal episodes that could be triggered by alcohol, coffee, exertion, emotion, or cigarette smoking. Brain MRI revealed mild cerebellar atrophy, and oculography showed a subclinical downbeat nystagmus. Treatment with acetazolamide resulted in remarkable improvement.Discussion:Paroxysmal dysarthria/ataxia should prompt the clinician to test for FGF14 repeat expansion/SCA27B, especially when the paroxysmal attacks are associated with late-onset cerebellar ataxia and/or a family history consistent with a dominant disorder.

BackgroundSomatosensory evoked potentials (SSEPs) help prognostication, particularly in patients with diffuse brain injury. However, use of SSEP is limited in critical care. We propose a novel, low-cost approach allowing acquisition of screening SSEP using widely available intensive care unit (ICU) equipment, specifically a peripheral "train-of-four" stimulator and standard electroencephalograph.MethodsThe median nerve was stimulated using a train-of-four stimulator, and a standard 21-channel electroencephalograph was recorded to generate the screening SSEP. Generation of the SSEP was supported by visual inspection, univariate event-related potentials statistics, and a multivariate support vector machine (SVM) decoding algorithm. This approach was validated in 15 healthy volunteers and validated against standard SSEPs in 10 ICU patients. The ability of this approach to predict poor neurological outcome, defined as death, vegetative state, or severe disability at 6 months, was tested in an additional set of 39 ICU patients.ResultsIn each of the healthy volunteers, both the univariate and the SVM methods reliably detected SSEP responses. In patients, when compared against the standard SSEP method, the univariate event-related potentials method matched in nine of ten patients (sensitivity = 94%, specificity = 100%), and the SVM had 100% sensitivity and specificity when compared with the standard method. For the 49 ICU patients, we performed both the univariate and the SVM methods: a bilateral absence of short latency responses (n = 8) predicted poor neurological outcome with 0% FPR (sensitivity = 21%, specificity = 100%).ConclusionsSomatosensory evoked potentials can reliably be recorded using the proposed approach. Given the very good but slightly lower sensitivity of absent SSEPs in the proposed screening approach, confirmation of absent SSEP responses using standard SSEP recordings is advised.

This study aimed at probing covert language processing in patients with disorders of consciousness. An auditory paradigm contrasting words to pronounceable pseudowords was designed, while recording bedside electroencephalogram and computing the two main correlates of lexicality: N400 and late positive component (LPC). Healthy volunteers and 19 patients, 10 in a minimally conscious state and 9 in a vegetative state (also coined unresponsive wakefulness syndrome), were recorded. N400 was present in all groups, whereas LPC was only present in the healthy volunteers and minimally conscious state groups. At the individual level, an unprecedented detection rate of N400 and LPC was reached, and LPC predicted overt cognitive improvement at 6 months. ANN NEUROL 2023;93:762–767

Little is known about risk factors for mortality in older patients with COVID‐19 and neuropsychiatric conditions.

Background Disorders of consciousness due to severe hypoglycemia are rare but challenging to treat. The aim of this retrospective cohort study was to describe our multimodal neurological assessment of patients with hypoglycemic encephalopathy hospitalized in the intensive care unit and their neurological outcomes. Methods Consecutive patients with disorders of consciousness related to hypoglycemia admitted for neuroprognostication from 2010 to 2020 were included. Multimodal neurological assessment included electroencephalography, somatosensory and cognitive event-related potentials, and morphological and quantitative magnetic resonance imaging (MRI) with quantification of fractional anisotropy. Neurological outcomes at 28 days, 3 months, 6 months, 1 year, and 2 years after hypoglycemia were retrieved. Results Twenty patients were included. After 2 years, 75% of patients had died, 5% remained in a permanent vegetative state, 10% were in a minimally conscious state, and 10% were conscious but with severe disabilities (Glasgow Outcome Scale-Extended scores 3 and 4). All patients showed pathologic electroencephalography findings with heterogenous patterns. Morphological brain MRI revealed abnormalities in 95% of patients, with various localizations including cortical atrophy in 65% of patients. When performed, quantitative MRI showed decreased fractional anisotropy affecting widespread white matter tracts in all patients. Conclusions The overall prognosis of patients with severe hypoglycemic encephalopathy was poor, with only a small fraction of patients who slowly improved after intensive care unit discharge. Of note, patients who did not improve during the first 6 months did not recover consciousness. This study suggests that a multimodal approach capitalizing on advanced brain imaging and bedside electrophysiology techniques could improve diagnostic and prognostic performance in severe hypoglycemic encephalopathy.

Hypnosis can be conceived as a unique opportunity to explore how top-down effects can influence various conscious and non-conscious processes. In the field of perception, such modulatory effects have been described in distinct sensory modalities. In the present study we focused on the auditory channel and aimed at creating a radical deafness to elementary sounds by a specific hypnotic suggestion. We report here a single case-study in a highly suggestible healthy volunteer who reported a total hypnotically suggested deafness. We recorded high-density scalp EEG during an auditory odd-ball paradigm before and after hypnotic deafness suggestion. While both early auditory event-related potentials to sounds (P1) and mismatch negativity component were not affected by hypnotic deafness, we observed a total disappearance of the late P3 complex component when the subject reported being deaf. Moreover, a centro-mesial positivity was present exclusively during the hypnotic condition prior to the P3 complex. Interestingly, source localization suggested an anterior cingulate cortex (ACC) origin of this neural event. Multivariate decoding analyses confirmed and specified these findings. Resting state analyses confirmed a similar level of conscious state in both conditions, and suggested a functional disconnection between auditory areas and other cortical areas. Taken together these results suggest the following plausible scenario: (i) preserved early processing of auditory information unaffected by hypnotic suggestion, (ii) conscious setting of an inhibitory process (ACC) preventing conscious access to sounds, (iii) functional disconnection between the modular and unconscious representations of sounds and global neuronal workspace. This single subject study presents several limits that are discussed and remains open to alternative interpretations. This original proof-of-concept paves the way to a larger study that will test the predictions stemming from our theoretical model and from this first report.

The clinical and fundamental exploration of patients suffering from disorders of consciousness (DoC) is commonly used by researchers both to test some of their key theoretical predictions and to serve as a unique source of empirical knowledge about possible dissociations between consciousness and cognitive and/or neural processes. For instance, the existence of states of vigilance free of any self-reportable subjective experience [e.g. "vegetative state (VS)" and "complex partial epileptic seizure"] originated from DoC and acted as a cornerstone for all theories by dissociating two concepts that were commonly equated and confused: vigilance and conscious state. In the present article, we first expose briefly the major achievements in the exploration and understanding of DoC. We then propose a synthetic taxonomy of DoC, and we finally highlight some current limits, caveats and questions that have to be addressed when using DoC to theorize consciousness. In particular, we show (i) that a purely behavioral approach of DoC is insufficient to characterize the conscious state of patients; (ii) that the comparison between patients in a minimally conscious state (MCS) and patients in a VS [also coined as unresponsive wakefulness syndrome (UWS)] does not correspond to a pure and minimal contrast between unconscious and conscious states and (iii) we emphasize, in the light of original resting-state positron emission tomography data, that behavioral MCS captures an important but misnamed clinical condition that rather corresponds to a cortically mediated state and that MCS does not necessarily imply the preservation of a conscious state.

Key Points Question Can electroencephalography (EEG), combined with clinical, biological, and magnetic resonance imaging (MRI) analyses, help to better characterize patients with neurologic coronavirus disease 2019 (COVID-19) and diagnose specific COVID-19–related encephalopathy? Findings Neurologic manifestations, biological findings, EEG findings, and brain MRI images were analyzed in a cohort study of 78 adult patients with COVID-19. Nine patients had no identified cause of brain injury, as revealed by biological and MRI findings; their injury was defined as COVID-19–related encephalopathy. Meaning This study suggests that, although neurologic manifestations, EEG findings, and MRI findings may appear heterogeneous and nonspecific, multimodal monitoring may better identify patients with COVID-19–related encephalopathy and guide treatment strategy.

Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p < 0.05). No significant differences in MST were observed between R and NR patients. Conclusion: The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.

Predicting the functional recovery of patients with severe neurological condition due to coronavirus disease 2019 (COVID-19) is a challenging task. Only limited outcome data are available, the pathophysiology is poorly understood, and the time-course of recovery is still largely unknown. Here, we report the case of a patient with COVID-19 associated encephalitis presenting as a prolonged state of unresponsiveness for two months, who finally fully recovered consciousness, functional communication, and autonomy after immunotherapy. In a multimodal approach, a high-density resting state EEG revealed a rich brain activity in spite of a severe clinical presentation. Using our previously validated algorithms, we could predict a possible improvement of consciousness in this patient. This case report illustrates the value of a multimodal approach capitalizing on advanced brain-imaging and bedside electrophysiology techniques to improve prognosis accuracy in this complex and new aetiology.

Neuronal mechanisms of Vagus nerve stimulation (VNS) efficacity in seizure control are not clearly understood. In animal models as in patients, VNS seems to produce desynchronization of interictal electroencephalography (EEG). We aim to confirm the role of EEG desynchronization as possible marker of VNS efficacity. We prospectively selected all EEG recordings of patients with drug resistant epilepsy treated by chronic VNS, recorded in our epileptology center from Jan 2017 to May 2018. EEG signals were acquired during a 30 min eyes-closed resting state period, using a 21 channel EEG system. Phase lag index (PLI), was used to calculate the functional connectivity strength on the first 16 artifact-free epochs for each condition (ON et OFF). Analyses were performed over a broad-filtered signal (0,5–70 Hz) and besides overs different sub-bands filtered signals. Patients were assigned to two different groups, responders (R: reduction >50% in seizure frequency) and non-responders (NR) Eighteen patients were included. Lower synchronization values were highlighted in R patients, compared to NR, in broadband signal and in sub-bands filtered signals. These differences were significantly demonstrated for alpha (p = 0,03, Mann–Whitney) and beta (p = 0,01, Mann–Whitney) bands. Lower synchronization values were as well lower in condition ON compared to condition OFF. These results confirm that the beneficial effect induced by VNS in seizure control is related to global interictal EEG desynchronization and that functional connectivity parameters could be used in clinical practice as potential predictor of VNS efficacity.