Minimally Conscious State

Disorders of consciousness (DoC) are severe neurological conditions characterized by impaired awareness and reduced interaction with the environment. Although hyperbaric oxygen therapy (HBOT) may promote neurological recovery, the optimal treatment strategy for individual patients remains unclear. This study aims to develop and validate an artificial intelligence-assisted precision decision support system for HBOT based on dynamic BIS-EEG brain functional feedback. The system will integrate clinical information, neuroimaging data, physiological parameters, consciousness assessments, and HBOT treatment characteristics. Continuous BIS-EEG monitoring will be performed during different phases of HBOT, including compression, oxygen exposure, air breaks, decompression, and post-treatment recovery. Artificial intelligence models will analyze these dynamic brain functional responses to predict treatment effectiveness and support personalized HBOT management. The primary outcome will be improvement in consciousness assessed by the Coma Recovery Scale-Revised (CRS-R). Secondary outcomes include changes in consciousness state, cognitive and functional recovery, and treatment-related adverse events.

After a severe brain injury some patients survive but cannot communicate, and deciding early which of them are likely to recover consciousness remains one of the hardest problems in neurocritical care. Bedside examination alone misclassifies a substantial proportion of these patients. CyDoC-MAP is a single-centre, prospective, observational cohort study conducted at Nicosia General Hospital, the sole trauma referral centre for Cyprus. It enrols patients aged 16 years or older who are intubated within 24 hours of a moderate-to-severe traumatic brain injury or a haemorrhagic stroke (intracerebral or subarachnoid haemorrhage), and who are subsequently classified as being in a vegetative state / unresponsive wakefulness syndrome (VS/UWS) or a minimally conscious state (MCS) on the Coma Recovery Scale-Revised (CRS-R). Four assessment modalities are recorded: (1) the CRS-R, performed at least twice with an interval of at least 48 hours; (2) serum neuron-specific enolase (NSE) sampled within 24 hours of intubation; (3) the bispectral index (BIS), recorded at least twice with an interval of at least 48 hours, after five minutes of standardised noxious and auditory stimulation; and (4) in the traumatic subgroup only, 1.5 T magnetic resonance imaging performed 7-28 days after injury and graded 1-4 by lesion depth by two independent raters. Level of consciousness is reassessed with the CRS-R 6 to 12 months after the index event, and the total CRS-R score (0-23) at that reassessment is the primary outcome. The primary aim is to estimate the strength of the association between the bispectral index recorded on the ward and that later CRS-R score, and to quantify what the bispectral index adds beyond the baseline clinical assessment. The number of eligible patients at a single national centre does not support the development of a prognostic model; the study is designed to produce effect-size estimates with confidence intervals that will inform a subsequent multicentre study. The study is purely observational. No intervention is administered, no study procedure alters clinical management, and transfer to rehabilitation is never delayed for research purposes.

The goal of this observational study is to learn whether functional near-infrared spectroscopy (fNIRS) can measure brain activity in healthy adults and in people with disorders of consciousness (DoC) in the neuro-intensive care unit (Neuro-ICU). DoC include conditions such as coma and minimally conscious state that occur after severe brain injury. These conditions make it difficult to assess a person's level of awareness because many clinical tests rely on observable behaviors such as speaking or moving, which are commonly impaired after brain injury. The main questions the study aims to answer are: * Can fNIRS detect changes in brain activity in healthy adults when they receive sensory stimulation or perform mental tasks? * Can the same fNIRS protocol be used in patients with disorders of consciousness in the Neuro-ICU to measure brain responses and determine whether the method is feasible in this clinical setting? The investigators will first study healthy adult volunteers to establish baseline brain responses and determine which tasks produce the most reliable signals. The protocol will then be applied to patients with disorders of consciousness admitted to the Neuro-ICU. Participants will take part in a single research session lasting about 30 to 45 minutes while wearing the lightweight fNIRS headband that measures brain oxygen levels using near-infrared light. During the session, participants will: * Wear a non-invasive fNIRS headband placed on the forehead * Receive gentle sensory stimulation (for example, compression devices on the legs or hands) * Listen to sounds or spoken sentences * Perform guided mental tasks such as imagining walking through their home or imagining moving a limb The study does not test a treatment and will not change medical care. The goal is to determine whether fNIRS can safely and reliably measure brain activity at the bedside and provide preliminary information that may help guide future research on improving the assessment of consciousness after brain injury.

The goal of this clinical trial is to learn if a new type of brain stimulation called theta-burst patterned temporal interference stimulation (tTIs) works to improve awareness in people with disorders of consciousness (DoC). The main questions it aims to answer are: 1. Does tTIs help people with disorders of consciousness show more signs of awareness? 2. Does tTIs improve the brain's ability to process information and connect different brain areas? Is tTIs safe and easy for people with disorders of consciousness to tolerate? Researchers will compare a group receiving active tTIs to a group receiving a "sham" stimulation (a look-alike stimulation that delivers no real current) to see if the real stimulation works better. Participants will:Receive either active tTIs or sham stimulation twice a day for 5 consecutive days (total of 10 sessions). Undergo brain activity tests (EEG) and physical exams to check their level of awareness before and after the 5 days of treatment. Have their progress followed by researchers through phone calls at 1, 3, and 6 months after the treatment ends.

Accurately determining the level of consciousness in patients with severe brain injury is essential for treatment planning, prognosis, and ethical decision-making. Clinically, levels of consciousness are differentiated into coma, Unresponsive Wakefulness Syndrome (UWS), and Minimally Conscious State (MCS) based on behavioral signs. Although behavioral assessment is considered the clinical gold standard, it is prone to misclassification. Research has shown that a substantial proportion of patients initially diagnosed with UWS may actually show signs of minimal consciousness, which is associated with better cognitive abilities and a more favorable prognosis. The Coma Recovery Scale-Revised (CRS-R) is internationally recommended for diagnosing disorders of consciousness, but it is time-consuming and not free from diagnostic error. Repeated assessments can significantly improve diagnostic accuracy. To enhance feasibility in routine clinical practice, a shorter and more time-efficient assessment tool, the Simplified Evaluation of CONsciousness Disorders (SECONDs), was developed. This scale focuses on the behavioral signs most strongly associated with MCS and uses optimized testing procedures while maintaining high diagnostic accuracy. The aim of this study is to further evaluate diagnostic approaches for assessing consciousness in patients with severe brain injury and to improve the reliability and clinical applicability of these assessments.

This prospective observational study investigates whether electroencephalography (EEG) can improve the differentiation between unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) in patients with severe acquired brain injury. The study further examines the association between EEG markers of auditory processing and long-term functional outcome at 12 months.

This study aims to explore the impact of Animal Assisted Therapy (AAT) on brain signal complexity in patients with minimally conscious state (MCS) by analyzing electroencephalogram (EEG) entropy. MCS patients typically exhibit reduced brain entropy compared to healthy individuals, indicating lower brain complexity. The study will assess whether AAT can enhance this complexity, which is crucial for understanding consciousness levels. Entropy, a measure of randomness in brain activity, will be used to evaluate AAT's effectiveness. In addition, electrocardiography (ECG), electrodermal activity (EDA) and behavioral measurements will also be collected.

The purpose of this academic lead study is to explore the effect of noninvasive neuromodulation of the CM-pf via tTIS for patients with disorders of consciousness.