Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness.

Objective: This study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors. Methods: This study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model. Result: The results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets. Conclusion: This study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.

Disorder of consciousness related pattern could distinguish minimally conscious state from unresponsive wakefulness syndrome: A F-18-FDG-PET study.

BACKGROUND: Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. OBJECTIVE: This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). METHODS: Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. RESULTS: The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P<0.0001, AUC=1.000), and furthermore could effectively distinguish MCS from UWS (P=0.037, AUC=0.821, sensitivity: 85.7 %, specificity: 75.0 %). Particularly in the subgroup of DOC patients survived global hypoxic-ischemic brain injury, DOCRP expression exhibited even better discriminatory power between MCS and UWS (P=0.046, AUC=1.000). CONCLUSIONS: DOCRP might serve as an objective biomarker in distinguishing between UWS and MCS, especially in patients survived global hypoxic-ischemic brain injury. TRIAL REGISTRATION NUMBER: ChiCTR2300073717 (Chinese clinical trial registry site, http://www.chictr.org).

Disorders of Consciousness.

This article reviews the definition, assessment, neuroimaging, treatment, and rehabilitation for disorders of consciousness after an acquired brain injury. It also explores special considerations and new neuromodulation treatment options.

[Neuromodulatory pharmacotherapy individualization in prolonged and chronic consciousness disorders after severe traumatic brain injury]. / K probleme individualizatsii neiromodulyatornoi farmakoterapii pri prolongirovannykh i khronicheskikh narusheniyakh soznaniya vsledstvie tyazheloi cherepno-mozgovoi travmy.

One of the most probable causes of effective therapy for post-comatose disorders of consciousness is the lack of individualization of drug prescriptions. In this observational study, we analyzed 48 courses of neuromodulatory therapy in 28 patients with prolonged and chronic disorders of consciousness following severe traumatic brain injury. Comparison of 24 effective and 24 ineffective courses demonstrated higher effectiveness of pharmacotherapy through its individualization, i.e. the choice of a drug whose neuromodulatory spectrum would correspond to neurological syndromes of neurotransmitter dysfunction. In this approach, 74% of therapy courses were effective while opposite management resulted only 34% of effective courses.

Analysis of Factors Related to the Efficacy of Consciousness-Regaining Therapy for Prolonged Disorder of Consciousness: A Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to the efficacy of consciousness-regaining therapy (CRT) for prolonged disorder of consciousness. METHODS: A retrospective analysis was conducted on the case data of 114 patients with prolonged disorder of consciousness (pDOC) admitted to the Department of Functional Neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022 to explore the relevant factors that affect the efficacy of CRT for pDOC. Next, basic information on the cases, data on pDOC disease assessment, CRT methods, and efficacy evaluation were collected. RESULTS: These 114 patients were grouped, and a comparative analysis was done based on the efficacy at the end of treatment. Of these, 61 cases were allotted to the ineffective group and 53 cases to the effective group. There was a lack of statistical difference (P > 0.05) between the 2 groups based on gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of CRT, and CRT duration (P > 0.05). However, secondary hydrocephalus, CRT methods, JFK Coma Recovery Scale-Revised grading before treatment, and extended Glasgow Outcome Scale score at six months after treatment were found to be statistically different. The results of binary logistic regression analysis showed that the type of therapy (OR = 0.169, 95% CI: 0.057-0.508) affected the efficacy of CRT (P < 0.05). CONCLUSIONS: Personalized awakening therapy using various invasive CRT methods could improve the efficacy of therapy for pDOC compared with noninvasive therapy.

Medicolegal issues and disorders of consciousness.

BACKGROUND: The tasks and responsibilities that come with clinician involvement in medicolegal proceedings can be daunting and particularly so in challenging areas such as provision of medicolegal opinions in cases involving disorders of consciousness (DoC). OBJECTIVE: The aim of this narrative review was to provide education and advice to healthcare practitioners who by choice or circumstance are asked and/or required to provide medicolegal opinions in cases involving patients with DoC. METHODS: A literature search was conducted using PubMed Central and MedlinePlus for articles dealing with clinician involvement in medicolegal cases involving persons with DoC. The information provided also integrates the authors' nearly 40 years of clinical experience, brain injury medicine practice and "trials and tribulations" associated with medicolegal involvement in such cases. RESULTS: The literature was found to be replete with articles on brain death and withdrawal/withholding of care (which are not the focus of this review). The extant medical literature in brain injury medicine on the other hand is currently lacking in practical information for clinicians working "in the trenches" regarding the challenges and caveats of medicolegal involvement in such cases. CONCLUSION: This review provides the reader with a big picture overview of the most pertinent medicolegal topics inherent in clinical work with patients with DOC including pertinent nomenclature, caveats regarding forensic consultation including independent medical examinations, testimony tips, discussion of life expectancy/median survival concepts, prognostication in a medicolegal context, documentation and record keeping as well as some of the specific challenges pertinent to these types of brain injury cases that are not per se relevant in less severe injuries.

Unconsciousness or unresponsiveness in akinetic mutism? Insights from a multimodal longitudinal exploration.

The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour-based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology-based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group in the Pediatric Population.

BACKGROUND: The fundamental gap obstructing forward progress of evidenced-based care in pediatric and neonatal disorders of consciousness (DoC) is the lack of defining consensus-based terminology to perform comparative research. This lack of shared nomenclature in pediatric DoC stems from the inherently recursive dilemma of the inability to reliably measure consciousness in the very young. However, recent advancements in validated clinical examinations and technologically sophisticated biomarkers of brain activity linked to future abilities are unlocking this previously formidable challenge to understanding the DoC in the developing brain. METHODS: To address this need, the first of its kind international convergence of an interdisciplinary team of pediatric DoC experts was organized by the Neurocritical Care Society's Curing Coma Campaign. The multidisciplinary panel of pediatric DoC experts proposed pediatric-tailored common data elements (CDEs) covering each of the CDE working groups including behavioral phenotyping, biospecimens, electrophysiology, family and goals of care, neuroimaging, outcome and endpoints, physiology and big Data, therapies, and pediatrics. RESULTS: We report the working groups' pediatric-focused DoC CDE recommendations and disseminate CDEs to be used in studies of pediatric patients with DoC. CONCLUSIONS: The CDEs recommended support the vision of progressing collaborative and successful internationally collaborative pediatric coma research.

Brain microstate spatio-temporal dynamics as a candidate endotype of consciousness.

Consciousness can be defined as a phenomenological experience continuously evolving. Current research showed how conscious mental activity can be subdivided into a series of atomic brain states converging to a discrete spatiotemporal pattern of global neuronal firing. Using the high temporal resolution of EEG recordings in patients with a severe Acquired Brain Injury (sABI) admitted to an Intensive Rehabilitation Unit (IRU), we detected a novel endotype of consciousness from the spatiotemporal brain dynamics identified via microstate analysis. Also, we investigated whether microstate features were associated with common neurophysiological alterations. Finally, the prognostic information comprised in such descriptors was analysed in a sub-cohort of patients with prolonged Disorder of Consciousness (pDoC). Occurrence of frontally-oriented microstates (C microstate), likelihood of maintaining such brain state or transitioning to the C topography and complexity were found to be indicators of consciousness presence and levels. Features of left-right asymmetric microstates and transitions toward them were found to be negatively correlated with antero-posterior brain reorganization and EEG symmetry. Substantial differences in microstates' sequence complexity and presence of C topography were found between groups of patients with alpha dominant background, cortical reactivity and antero-posterior gradient. Also, transitioning from left-right to antero-posterior microstates was found to be an independent predictor of consciousness recovery, stronger than consciousness levels at IRU's admission. In conclusions, global brain dynamics measured with scale-free estimators can be considered an indicator of consciousness presence and a candidate marker of short-term recovery in patients with a pDoC.

Clinical neuromodulatory effects of deep brain stimulation in disorder of consciousness: A literature review.

BACKGROUND: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions. OBJECTIVE: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients. METHODS: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science). RESULTS: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian-parafascicular complex (CM-pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 µs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow-up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates. CONCLUSION: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population.

The Immediate Effects of Immersive Virtual Reality on Autonomic Nervous System Function in Patients with Disorders of Consciousness after Severe Acquired Brain Injury: A Pilot Study.

Disorders of Consciousness (DoCs) after severe acquired brain injury involve substantial impairment of cognition and physical functioning, requiring comprehensive rehabilitation and support. Technological interventions, such as immersive Virtual Reality (VR), have shown promising results in promoting neural activity and enhancing cognitive and motor recovery. VR can induce physical sensations that may activate the Autonomic Nervous System (ANS) and induce ANS-regulated responses. This study aimed to investigate the effects of immersive VR on the ANS in patients with DoCs through the analysis of the electrodermal activity (EDA). EDA was measured with a wearable device during a single immersive VR session consisting of static and dynamic videos depicting naturalistic environments. A pilot case-control study was conducted with 12 healthy participants and 12 individuals with DoCs. Results showed higher EDA values in patients than in healthy participants (p = 0.035), suggesting stronger autonomic activation during immersive VR exposure, while healthy subjects, in turn, showed a decrease in EDA values. Our results revealed a significant interaction between conditions and groups (p = 0.003), with patients showing significantly increased EDA values from the baseline compared to dynamic video observation (p = 0.014) and final rest (p = 0.007). These results suggest that immersive VR can elicit sympathetic arousal in patients with DoCs. This study highlights the potential of immersive VR as a tool to strengthen autonomic responses in patients with impaired consciousness.

Clinical application of neuromodulation therapy in patients with disorder of consciousness: A pooled analysis of 544 participants.

BACKGROUND: The number of patients with disorders of consciousness (DoC) has increased dramatically with the advancement of intensive care and emergency medicine, which brings tremendous economic burdens and even ethical issues to families and society. OBJECTIVE: To evaluate the effectiveness of neuromodulation therapy for patients with DoC. METHODS: First, we conducted a literature review of individual patient data (IPD) on PubMed, EMBASE, and Cochrane-controlled trials following PRISMA guidelines. Then, we collected neuromodulation cases from our institution. Finally, we conducted a pooled analysis using the participants from the medical literature (n = 522) and our local institutions (n = 22). RESULTS: In this pooled analysis of 544 patients with DoC with a mean age of 46.33 years, our results revealed that patients have improved CRS-R scores [1.0 points (95% CI, 0.57-1.42)] after neuromodulation. Among them, patients have better effectiveness in traumatic than non-traumatic etiology (P < 0.05). The effectiveness of consciousness improvement could be affected by the age, baseline consciousness state, and duration of stimulation. Compared with non-invasive intervention, an invasive intervention can bring more behavioral improvement (P < 0.0001) to MCS rather than UWS/VS patients. Importantly, neuromodulation is a valuable therapy even years after the onset of DoC. CONCLUSION: This pooled analysis spotlights that the application of neuromodulation can improve the behavioral performance of patients with DoC. A preliminary trend is that age, etiology, baseline consciousness state, and stimulation duration could impact its effectiveness.

Presumed first episode of nonconvulsive status epilepticus as the cause of postoperative disorder of consciousness following the completion of general anesthesia: A case report.

Key Clinical Message: Disorder of consciousness can lead to irreversible sequelae without proper intervention. Consequently, early diagnosis and treatment are of paramount importance in patients with disorder of consciousness. Abstract: Disorder of consciousness (DOC) has various etiologies. Here, we report a case in which DOC following general anesthesia was suspected as being due to the first episode of nonconvulsive status epilepticus (NCSE). An elderly man in his 80s underwent uneventful tumor resection surgery under general anesthesia for extramammary Paget's disease. After the procedure, he regained consciousness following anesthesia discontinuation and was extubated. Soon after extubation, however, although his respiratory status remained stable, his level of consciousness deteriorated to a Glasgow Coma Scale (GCS) score of E1V1M1. Head computed tomography and magnetic resonance imaging scans indicated no abnormal findings. Subsequently, involuntary movements were noted in his left upper limb. Suspecting an epilepsy episode, diazepam was administered, leading to an improvement in the level of consciousness (GCS: E4V5M6). Based on the improvement in consciousness after diazepam administration, we strongly suspected NCSE.

Resting-state EEG microstates as electrophysiological biomarkers in post-stroke disorder of consciousness.

Introduction: Ischemic stroke patients commonly experience disorder of consciousness (DOC), leading to poorer discharge outcomes and higher mortality risks. Therefore, the identification of applicable electrophysiological biomarkers is crucial for the rapid diagnosis and evaluation of post-stroke disorder of consciousness (PS-DOC), while providing supportive evidence for cerebral neurology. Methods: In our study, we conduct microstate analysis on resting-state electroencephalography (EEG) of 28 post-stroke patients with awake consciousness and 28 patients with PS-DOC, calculating the temporal features of microstates. Furthermore, we extract the Lempel-Ziv complexity of microstate sequences and the delta/alpha power ratio of EEG on spectral. Statistical analysis is performed to examine the distinctions in features between the two groups, followed by inputting the distinctive features into a support vector machine for the classification of PS-DOC. Results: Both groups obtain four optimal topographies of EEG microstates, but notable distinctions are observed in microstate C. Within the PS-DOC group, there is a significant increase in the mean duration and coverage of microstates B and C, whereas microstate D displays a contrasting trend. Additionally, noteworthy variations are found in the delta/alpha ratio and Lempel-Ziv complexity between the two groups. The integration of the delta/alpha ratio with microstates' temporal and Lempel-Ziv complexity features demonstrates the highest performance in the classifier (Accuracy = 91.07%). Discussion: Our results suggest that EEG microstates can provide insights into the abnormal brain network dynamics in DOC patients post-stroke. Integrating the temporal and Lempel-Ziv complexity microstate features with spectral features offers a deeper understanding of the neuro mechanisms underlying brain damage in patients with DOC, holding promise as effective electrophysiological biomarkers for diagnosing PS-DOC.

A cross-subject decoding algorithm for patients with disorder of consciousness based on P300 brain computer interface.

Background: Brain computer interface (BCI) technology may provide a new way of communication for some patients with disorder of consciousness (DOC), which can directly connect the brain and external devices. However, the DOC patients' EEG differ significantly from that of the normal person and are difficult to collected, the decoding algorithm currently only is trained based on a small amount of the patient's own data and performs poorly. Methods: In this study, a decoding algorithm called WD-ADSTCN based on domain adaptation is proposed to improve the DOC patients' P300 signal detection. We used the Wasserstein distance to filter the normal population data to increase the training data. Furthermore, an adversarial approach is adopted to resolve the differences between the normal and patient data. Results: The results showed that in the cross-subject P300 detection of DOC patients, 7 of 11 patients achieved an average accuracy of over 70%. Furthermore, their clinical diagnosis changed and CRS-R scores improved three months after the experiment. Conclusion: These results demonstrated that the proposed method could be employed in the P300 BCI system for the DOC patients, which has important implications for the clinical diagnosis and prognosis of these patients.

Neuropsychological Assessment in Patients with Traumatic Brain Injury: A Comprehensive Review with Clinical Recommendations.

Traumatic brain injury is damage to the brain occurring after birth, often resulting in the deterioration of cognitive, behavioural, and emotional functions. Neuropsychological evaluation can assist clinicians to better assess the patient's clinical condition, reach differential diagnoses, and develop interventional strategies. However, considering the multiple rating scales available, it is not easy to establish which tool is most suitable for the different brain injury conditions. The aim of this review is to investigate and describe the most used neurocognitive assessment tools in patients with traumatic brain injury to provide clinicians with clear indications on their use in clinical practice. Indeed, during the acute phase, after the head trauma, alertness and wakefulness of the patients affected by a disorder of consciousness can be assessed using different scales, such as the Coma Recovery Scale-Revised. In both postacute and chronic phases after traumatic brain injury, general cognitive assessment tools (such as the Mini Mental State Examination) or more specific cognitive tests (e.g., Wisconsin Card Sorting Test and Trail Making Test) could be administered according to the patient's functional status. In this way, clinicians may be aware of the patient's neuropsychological and cognitive level, so they can guarantee a personalized and tailored rehabilitation approach in this frail patient population.

EEG fractal dimensions predict high-level behavioral responses in minimally conscious patients.

Objective.Brain-injured patients may enter a state of minimal or inconsistent awareness termed minimally conscious state (MCS). Such patient may (MCS+) or may not (MCS-) exhibit high-level behavioral responses, and the two groups retain two inherently different rehabilitative paths and expected outcomes. We hypothesized that brain complexity may be treated as a proxy of high-level cognition and thus could be used as a neural correlate of consciousness.Approach.In this prospective observational study, 68 MCS patients (MCS-: 30; women: 31) were included (median [IQR] age 69 [20]; time post-onset 83 [28]). At admission to intensive rehabilitation, 30 min resting-state closed-eyes recordings were performed together with consciousness diagnosis following international guidelines. The width of the multifractal singularity spectrum (MSS) was computed for each channel time series and entered nested cross-validated interpretable machine learning models targeting the differential diagnosis of MCS±.Main results.Frontal MSS widths (p< 0.05), as well as the ones deriving from the left centro-temporal network (C3:p= 0.018, T3:p= 0.017; T5:p= 0.003) were found to be significantly higher in the MCS+ cohort. The best performing solution was found to be the K-nearest neighbor model with an aggregated test accuracy of 75.5% (median [IQR] AuROC for 100 executions 0.88 [0.02]). Coherently, the electrodes with highest Shapley values were found to be Fz and Cz, with four out the first five ranked features belonging to the fronto-central network.Significance.MCS+ is a frequent condition associated with a notably better prognosis than the MCS-. High fractality in the left centro-temporal network results coherent with neurological networks involved in the language function, proper of MCS+ patients. Using EEG-based interpretable algorithm to complement differential diagnosis of consciousness may improve rehabilitation pathways and communications with caregivers.

Aberrant temporal correlations of ongoing oscillations in disorders of consciousness on multiple time scales.

Changes in neural oscillation amplitude across states of consciousness has been widely reported, but little is known about the link between temporal dynamics of these oscillations on different time scales and consciousness levels. To address this question, we analyzed amplitude fluctuation of the oscillations extracted from spontaneous resting-state EEG recorded from the patients with disorders of consciousness (DOC) and healthy controls. Detrended fluctuation analysis (DFA) and measures of life-time and waiting-time were employed to characterize the temporal structure of EEG oscillations on long time scales (1-20 s) and short time scales (< 1 s), in groups with different consciousness states: patients in minimally conscious state (MCS), patients with unresponsive wakefulness syndrome (UWS) and healthy subjects. Results revealed increased DFA exponents that implies higher long-range temporal correlations (LRTC), especially in the central brain area in alpha and beta bands. On short time scales, declined bursts of oscillations were also observed. All the metrics exhibited lower individual variability in the UWS or MCS group, which may be attributed to the reduced spatial variability of oscillation dynamics. In addition, the temporal dynamics of EEG oscillations showed significant correlations with the behavioral responsiveness of patients. In summary, our findings shows that loss of consciousness is accompanied by alternation of temporal structure in neural oscillations on multiple time scales, and thus may help uncover the mechanism of underlying neuronal correlates of consciousness. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09852-9.

Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol.

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper.