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Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness

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A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurorehabilitation".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 13702

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Dr. Yang Bai

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Guest Editor

1. Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
2. Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China
Interests: EEG; TMS; TMS-EEG; non-invasive brain stimulation; disorders of consciousness

Special Issue Information

Dear Colleagues,

With the development of emergency rooms and intensive care units, the mortality rate of patients after severe brain injury has significantly decreased. However, many patients who survive the initial phase of cerebral coma move on to a potentially long-lasting or even permanent disorder of consciousness (DOC) state. DOC is generally caused by injury or dysfunction of the neural systems regulating arousal and awareness. DOC patients show an absence of arousal (i.e., eye opening when stimulated) and awareness (unaware of themselves and the environment). Patients who remain unresponsive to external stimulation or only show simple reflex movements that are uncorrelated with command are diagnosed with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Patients who show fluctuating but definite behavioral evidence of self or environmental awareness are diagnosed as being in a minimally conscious state (MCS).

The large number of DOC patients has brought immense challenges to our healthcare systems. Poor understanding of the pathophysiological mechanisms of (un)consciousness makes it difficult to carry out the precise assessment, management and treatment of DOC patients. Patients often remain in a tragic situation of “can’t die and can’t be cured” for a long time.

Residual consciousness and brain functions are critical pieces of information that directly affect treatment decisions and management settings. In clinical practice, a behavioral scale (Coma Recovery Scale, CRS-R) is widely used to assess the state of consciousness of patients. However, this method is complicated, time-consuming, labor-intensive and suffers from a high rate of misdiagnosis. Recently, innovative neuroimaging and electrophysiological techniques (e.g., fMRI, PET, fNIRS, EEG, ERP and TMS-EEG) have allowed for a more precise and individual assessment of residual brain functions with the promise to facilitate a better diagnosis, monitoring and treatment of DOC patients.

Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) or transcranial ultrasound (tUS) are painless, safe, inexpensive and adaptable and have, therefore, recently attracted major interest as possible treatment tools for DOC patients.

This Research Topic aims at providing updates on the pathophysiological mechanisms of disorders of consciousness as tested with advanced neuroimaging and electrophysiological techniques, and on the neuromodulation strategies for the treatment of DOC patients.

Dr. Yang Bai
Guest Editor

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Keywords

disorders of consciousness
unresponsive wakefulness syndrome
minimally conscious state
neuromodulation
neuroimaging, electrophysiology
neurorehabilitation

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Published Papers (9 papers)

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Research

14 pages, 1008 KiB

Open AccessArticle

The Role of Life History Questionnaires in Defining Individualised Goals of Care for Clinical Cognitive Motor Dissociation Patients: A Pilot Study

by Yago Rodriguez Mateos, Karin Diserens, Jennyfer Becquet, Etienne Rochat, Ralf J. Jox and Ivo A. Meyer

Brain Sci. 2025, 15(3), 267; https://doi.org/10.3390/brainsci15030267 - 1 Mar 2025

Viewed by 645

Abstract

Background/Objectives: The aim of this pilot study is to qualitatively describe the use of life history questionnaires in an acute neurorehabilitation setting to define individualised goals of care for patients with clinical cognitive motor dissociation and to determine to what extent the information they contain influences the care and management provided by the team. Methods: Using the patient records of our sample, all individualised goals of care were summarised, which were subsequently used to assess whether life history questionnaires had supplied sufficient information to define various individualised goals of care. We then conducted semi-structured interviews with the involved healthcare professionals to gain insights on how these questionnaires were used. Results: Approximately one-third of all individualised goals of care belonging to the “Activities and Participation” ICF category were defined through life history questionnaires. The semi-structured interviews highlighted the impact of these questionnaires in three main aspects: creating a therapeutic alliance with the patient, facilitating multidisciplinary cohesion, and nurturing a sense of empathy amongst the healthcare professionals. Conclusions: Life history questionnaires are an important contribution to individualised goals of care and may improve the relationship with the patient and the therapeutic setting for all healthcare professionals involved. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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18 pages, 5593 KiB

Open AccessArticle

Decoding Analyses Show Dynamic Waxing and Waning of Event-Related Potentials in Coma Patients

by Adianes Herrera-Diaz, Rober Boshra, Richard Kolesar, Netri Pajankar, Paniz Tavakoli, Chia-Yu Lin, Alison Fox-Robichaud and John F. Connolly

Brain Sci. 2025, 15(2), 189; https://doi.org/10.3390/brainsci15020189 - 13 Feb 2025

Viewed by 771

Abstract

Background/Objectives: Coma prognosis is challenging, as patient presentation can be misleading or uninformative when using behavioral assessments only. Event-related potentials have been shown to provide valuable information about a patient’s chance of survival and emergence from coma. Our prior work revealed that the mismatch negativity (MMN) in particular waxes and wanes across 24 h in some coma patients. This “cycling” aspect of the presence/absence of neurophysiological responses may require fine-grained tools to increase the chances of detecting levels of neural processing in coma. This study implements multivariate pattern analysis (MVPA) to automatically quantify patterns of neural discrimination between duration deviant and standard tones over time at the single-subject level in seventeen healthy controls and in three comatose patients. Methods: One EEG recording, containing up to five blocks of an auditory oddball paradigm, was performed in controls over a 12 h period. For patients, two EEG sessions were conducted 3 days apart for up to 24 h, denoted as day 0 and day 3, respectively. MVPA was performed using a support-vector machine classifier. Results: Healthy controls exhibited reliable discrimination or classification performance during the latency intervals associated with MMN and P3a components. Two patients showed some intervals with significant discrimination around the second half of day 0, and all had significant results on day 3. Conclusions: These findings suggest that decoding analyses can accurately classify neural responses at a single-subject level in healthy controls and provide evidence of small but significant changes in auditory discrimination over time in coma patients. Further research is needed to confirm whether this approach represents an improved technology for assessing cognitive processing in coma. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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12 pages, 225 KiB

Open AccessArticle

Italian Coma Recovery Scale for Pediatrics (CRS-P): Preliminary Validation in a Sample of Young Children with Typical Development

by Katia Colombo, Claudia Corti, Chiara Porro, Claudia Fedeli, Monica Beschi, Cristina Reverberi and Sandra Strazzer

Brain Sci. 2025, 15(2), 118; https://doi.org/10.3390/brainsci15020118 - 26 Jan 2025

Viewed by 970

Abstract

Background/Objectives: Guidelines for the diagnosis of children with disorder of consciousness (DoC) in pediatric age have not been defined yet. Assessment tools designed for adults have generally not been standardized for pediatrics, which could lead to misdiagnosis due to the limited behavioral repertoire of children. This study aims at examining the basic psychometric properties of the Italian Coma Recovery Scale for Pediatrics (CRS-P) in typically developing children. Methods: A total of 64 typically developing children aged 3 months to 5:7 years were administered the CRS-P. Performance was examined across the age range, and for the two behaviors indicating emergence to a conscious state, namely functional object use (FOU) and functional communication (FC). Results: Inter-rater reliability ranged from 0.95 to 1 for subscale and total scores. All children aged ≥34 months scored at the CRS-P ceiling. All children ≥ 14 months met the criteria for FOU and all children ≥ 34 months met those for FC. Children as early as 3 months of age displayed behaviors discriminating between vegetative state (VS) and minimally conscious state (MCS) in the Visual and Motor subscales. Language-based behaviors of MCS in other subscales were consistently displayed by older children. Conclusions: Typically developing children met the criteria for all items of the Italian CRS-P by 34 months, which suggests caution in adopting the scale at a younger age. However, the features of the distinct stages of DoC could be captured earlier, based on the various subscales. Modifications should be made to some items to improve diagnostic accuracy. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

11 pages, 539 KiB

Open AccessArticle

Optimizing Neurobehavioral Assessment for Patients with Disorders of Consciousness: Proposal of a Comprehensive Pre-Assessment Checklist for Clinicians

by Kristen Keech, Caroline Schnakers, Brooke Murtaugh, Katherine O’Brien, Beth Slomine, Marie-Michèle Briand, Rita Formisano, Aurore Thibaut, Anna Estraneo, Enrique Noé, Olivia Gosseries and Liliana da Conceição Teixeira

Brain Sci. 2025, 15(1), 71; https://doi.org/10.3390/brainsci15010071 - 15 Jan 2025

Viewed by 1179

Abstract

Background: Clinicians are challenged by the ambiguity and uncertainty in assessing level of consciousness in individuals with disorder of consciousness (DoC). There are numerous challenges to valid and reliable neurobehavioral assessment and classification of DoC due to multiple environmental and patient-related biases including behavioral fluctuation and confounding or co-occurring medical conditions. Addressing these biases could impact accuracy of assessment and is an important aspect of the DoC assessment process. Methods: A pre-assessment checklist was developed by a group of interdisciplinary DoC clinical experts and researchers based on the existing literature, current validated tools, and expert opinions. Once finalized, the checklist was electronically distributed to clinicians with a range of experience in neurobehavioral assessment with DoC. Respondents were asked to use the checklist prior to completing a neurobehavioral assessment. A survey was also provided to respondents to obtain feedback regarding checklist feasibility and utility in optimizing the behavioral assessments. Results: Thirty-three clinicians completed the survey after using the checklist. Over half of the respondents were a combination of physicians, neuropsychologists, and physical therapists. All respondents served the adult DoC population and 42% percent had over ten years of clinical experience. Eighty percent reported they found the format of the checklist useful and easy to use. All respondents reported the checklist was relevant to preparing for behavioral assessment in the DoC population. Eighty-four percent reported they would recommend the use of the tool to other clinicians. Conclusions: The use of a pre-assessment checklist was found to be feasible and efficacious in increasing interdisciplinary clinician’s ability to optimize the patient and environment in preparation for neurobehavioral assessment. Initial results of clinicians’ perception of the utility of a pre-assessment checklist were positive. However, further validation of the tool is needed with larger sample sizes to improve representation of clinical use across disciplines and care settings. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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15 pages, 5828 KiB

Open AccessArticle

Electroencephalography (EEG) for Neurological Prognostication in Post-Anoxic Coma Following Cardiac Arrest and Its Relationship to Outcome

by Zaitoon Shivji, Nathaniel Bendahan, Carter McInnis, Timothy Woodford, Michael Einspenner, Lisa Calder, Lysa Boissé Lomax, Garima Shukla and Gavin P. Winston

Brain Sci. 2024, 14(12), 1264; https://doi.org/10.3390/brainsci14121264 - 17 Dec 2024

Viewed by 1681

Abstract

Background/Objectives: Cardiac arrest may cause significant hypoxic–ischemic injury leading to coma, seizures, myoclonic jerks, or status epilepticus. Mortality is high, but accurate prognostication is challenging. A multimodal approach is employed, in which electroencephalography (EEG) forms a key part with several recognised patterns of prognostic significance. Methods: In this retrospective study, clinical and qualitative features of the EEG of patients admitted to the Intensive Care Unit (ICU) at Kingston General Hospital following cardiac arrest from 2017 to 2020 were reviewed. The study included 81 adult patients (≥18 years). Outcome was assessed using the Cerebral Performance Category (CPC) as 1–2 (favourable) or 3–5 (unfavourable). EEG patterns were divided into groups within the highly malignant, malignant and benign patterns described in the literature. Results: There were a wide range of causes and 22% had a favourable outcome. Highly malignant, malignant and benign patterns were associated with survival in 0%, 70% and 100%, respectively, and favourable outcomes in 0%, 48% and 100%. All patients with seizures died, and 94% with myoclonus had unfavourable outcomes. In contrast, EEG reactivity and improvement on follow-up EEG were associated with a favourable outcome. Conclusions: Highly malignant EEG, seizures and myoclonus were associated with unfavourable outcomes, while patients with malignant EEG had better outcomes. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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16 pages, 2173 KiB

Open AccessArticle

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study

by Matthias Manfred Deininger, Miriam Weiss, Stephanie Wied, Alexandra Schlycht, Nico Haehn, Gernot Marx, Anke Hoellig, Gerrit Alexander Schubert and Thomas Breuer

Brain Sci. 2024, 14(9), 849; https://doi.org/10.3390/brainsci14090849 - 23 Aug 2024

Cited by 2 | Viewed by 1250

Abstract

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70–140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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11 pages, 1112 KiB

Open AccessArticle

MutaPT: A Multi-Task Pre-Trained Transformer for Classifying State of Disorders of Consciousness Using EEG Signal

by Zihan Wang, Junqi Yu, Jiahui Gao, Yang Bai and Zhijiang Wan

Brain Sci. 2024, 14(7), 688; https://doi.org/10.3390/brainsci14070688 - 10 Jul 2024

Cited by 3 | Viewed by 1519

Abstract

Deep learning (DL) has been demonstrated to be a valuable tool for classifying state of disorders of consciousness (DOC) using EEG signals. However, the performance of the DL-based DOC state classification is often challenged by the limited size of EEG datasets. To overcome this issue, we introduce multiple open-source EEG datasets to increase data volume and train a novel multi-task pre-training Transformer model named MutaPT. Furthermore, we propose a cross-distribution self-supervised (CDS) pre-training strategy to enhance the model’s generalization ability, addressing data distribution shifts across multiple datasets. An EEG dataset of DOC patients is used to validate the effectiveness of our methods for the task of classifying DOC states. Experimental results show the superiority of our MutaPT over several DL models for EEG classification. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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11 pages, 1299 KiB

Open AccessArticle

EEG Changes during Propofol Anesthesia Induction in Vegetative State Patients Undergoing Spinal Cord Stimulation Implantation Surgery

by Xuewei Qin, Xuanling Chen, Bo Wang, Xin Zhao, Yi Tang, Lan Yao, Zhenhu Liang, Jianghong He and Xiaoli Li

Brain Sci. 2023, 13(11), 1608; https://doi.org/10.3390/brainsci13111608 - 20 Nov 2023

Cited by 1 | Viewed by 2151

Abstract

Objective: To compare the EEG changes in vegetative state (VS) patients and non-craniotomy, non-vegetative state (NVS) patients during general anesthesia with low-dose propofol and to find whether it affects the arousal rate of VS patients. Methods: Seven vegetative state patients (VS group: five with traumatic brain injury, two with ischemic–hypoxic VS) and five non-craniotomy, non-vegetative state patients (NVS group) treated in the Department of Neurosurgery, Peking University International Hospital from January to May 2022 were selected. All patients were induced with 0.5 mg/kg propofol, and the Bispectral Index (BIS) changes within 5 min after administration were observed. Raw EEG signals and perioperative EEG signals were collected and analyzed using EEGLAB in the MATLAB software environment, time–frequency spectrums were calculated, and EEG changes were analyzed using power spectrums. Results: There was no significant difference in the general data before surgery between the two groups (p > 0.05); the BIS reduction in the VS group was significantly greater than that in the NVS group at 1 min, 2 min, 3 min, 4 min, and 5 min after 0.5 mg/kg propofol induction (p < 0.05). Time–frequency spectrum analysis showed the following: prominent α band energy around 10 Hz and decreased high-frequency energy in the NVS group, decreased high-frequency energy and main energy concentrated below 10 Hz in traumatic brain injury VS patients, higher energy in the 10–20 Hz band in ischemic–hypoxic VS patients. The power spectrum showed that the brain electrical energy of the NVS group was weakened R5 min after anesthesia induction compared with 5 min before induction, mainly concentrated in the small wave peak after 10 Hz, i.e., the α band peak; the energy of traumatic brain injury VS patients was weakened after anesthesia induction, but no α band peak appeared; and in ischemic–hypoxic VS patients, there was no significant change in low-frequency energy after anesthesia induction, high-frequency energy was significantly weakened, and a clear α band peak appeared slightly after 10 Hz. Three months after the operation, follow-up visits were made to the VS group patients who had undergone SCS surgery. One patient with traumatic brain injury VS was diagnosed with MCS-, one patient with ischemic–hypoxic VS had increased their CRS-R score by 1 point, and the remaining five patients had no change in their CRS scores. Conclusions: Low doses of propofol cause great differences in the EEG of different types of VS patients, which may be the unique response of damaged nerve cell residual function to propofol, and these weak responses may also be the basis of brain recovery Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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13 pages, 3471 KiB

Open AccessArticle

A Comparison of the Neuromodulation Effects of Frontal and Parietal Transcranial Direct Current Stimulation on Disorders of Consciousness

by Xiaoping Wan, Yong Wang, Ye Zhang and Weiqun Song

Brain Sci. 2023, 13(9), 1295; https://doi.org/10.3390/brainsci13091295 - 8 Sep 2023

Cited by 1 | Viewed by 1544

Abstract

Frontal transcranial direct current stimulation (tDCS) and parietal tDCS are effective for treating disorders of consciousness (DoC); however, the relative efficacies of these techniques have yet to be determined. This paper compares the neuromodulation effects of frontal and parietal tDCS on DoC. Twenty patients with DoC were recruited and randomly assigned to two groups. One group received single-session frontal tDCS and single-session sham tDCS. The other group received single-session parietal tDCS and single-session sham tDCS. Before and after every tDCS session, we recorded coma recovery scale-revised (CRS-R) values and an electroencephalogram. CRS-R was also used to evaluate the state of consciousness at 9–12-month follow-up. Both single-session frontal and parietal tDCS caused significant changes in the genuine permutation cross-mutual information (G_PCMI) of local frontal and across brain regions (p < 0.05). Furthermore, the changes in G_PCMI values were significantly correlated to the CRS-R scores at 9–12-month follow-up after frontal and parietal tDCS (p < 0.05). The changes in G_PCMI and CRS-R scores were also correlated (p < 0.05). Both frontal tDCS and parietal tDCS exert neuromodulatory effects in DoC and induce significant changes in electrophysiology. G_PCMI can be used to evaluate the neuromodulation effects of tDCS. Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

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