Severe Traumatic Brain Injury

Severe Traumatic brain injury (sTBI) is a very serious problem, and right now, doctors don't have special treatments to help stop additional injury. Previous studies showed that when a young person gets this kind of brain injury, their body's defense system reacts quickly and strongly. This can cause problems with the brain's protective barrier breaking down and the body making antibodies that attack its own cells. We think that changes in how the brain and the gut (the part of your body that digests food) talk to each other might make these defense reactions stronger. This study wants to figure out exactly how brain injuries change the gut and how that affects the body's defenses. To do this, we will use new ways to study body chemicals and genes \[RNA, cell free DNA (cfDNA) and blood chemistry\] to help us learn why the body reacts this way and how it can lead to more brain injuries and problems in adults with serious brain injuries.

The LIMIT-TBI trial is a multicenter, international, randomized, phase II clinical trial designed to evaluate the feasibility and safety of targeting a neutral fluid balance compared to standard care in critically ill adult patients with traumatic brain injury (TBI). Fluid therapy is a cornerstone of TBI management, but optimal fluid balance remains uncertain, with both fluid overload and restriction potentially leading to adverse outcomes. This study aims to determine whether maintaining a daily fluid balance close to zero (±500 mL) during the first 5 days of ICU admission is achievable and safe. Participants will be randomized within 48 hours of ICU admission to either a protocolized neutral fluid balance strategy or standard care. Outcomes include feasibility of achieving the target balance, organ complications, hemodynamic parameters, ICU resource utilization, and mortality and neurological outcomes up to 6 months.

Objective: This prospective interventional study introduces "SeeMe," an automated, high-resolution computer vision platform designed to objectively quantify microscopic, auditory command-evoked movements in patients with Traumatic Brain Injury (TBI). Current clinical assessments, such as the Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R), rely on subjective human observation and often fail to detect low-amplitude motor responses, potentially misclassifying up to 25% of patients as unresponsive. Methodology: SeeMe utilizes vector analysis, cross-correlation, and deep neural networks (DNNs) to track individual facial pores and hand movements with sub-millimeter precision (0.5 mm) and high temporal resolution (0.03s). The study will enroll a cohort of 60-80 TBI patients, alongside healthy controls and pharmacologically paralyzed subjects, to validate SeeMe's sensitivity and specificity. Primary Goals: 1. Validation: Compare SeeMe's detection of voluntary motor recovery against gold-standard clinical examinations (CRS-R). 2. Synchronization: Simultaneously record and time-lock electroencephalography (EEG) and electrocorticography (ECoG) with SeeMe-detected movements. 3. Biomarker Identification: Characterize neural signatures (specifically Beta-band oscillations) associated with the return of voluntary behavior. Impact: By providing a real-time, objective measure of motor intention and execution, SeeMe aims to identify "Cognitive-Motor Dissociation" (CMD) earlier than current methods, facilitating more accurate prognostications and laying the framework for future closed-loop neuromodulation (e.g., Vagus Nerve Stimulation) to accelerate TBI recovery.

The goal of this phase 1 randomized controlled safety and feasibility clinical trial are to determine the safety of external lumbar drainage (ELD) in select patients with severe Traumatic Brain Injury (TBI). The main questions it aims to answer are (i) if ELD is feasible and (ii) safe to perform in severe TBI patients who have radiological evidence of patent basal cisterns and midline shift \<5mm without increasing the risk of neurological worsening or cerebral herniation. All participants will receive routine usual care. The study group will additionally have ELD for cerebrospinal fluid (CSF) drainage. A comparison will be made between the usual treatment plus ELD (interventional) groups, and the usual treatment (control) groups on incidence rate of neurological worsening or cerebral herniation events, and whether total hours with raised intracranial pressure (ICP) are different.

Traumatic brain injury and other severe brain injuries requiring neurointensive care are associated with high mortality, long-term disability and substantial societal burden. Despite advances in critical care, outcomes after severe brain injury remain difficult to predict and secondary brain injury plays a major role in determining prognosis. The Örebro Severe Brain Injury Database (ÖrSBID) is a prospective observational registry that aims to systematically collect detailed clinical, physiological, imaging and biological data from adult patients with severe brain injury requiring care at the neurointesive care unit or neurointermediate care unit at Örebro University Hospital. The purpose of the registry is to enable deep phenotyping of severe brain injury, improve understanding of secondary injury mechanisms, support outcome prediction and provide a platform for longitudinal follow-up and future research. No experimental interventions are performed as part of the study.

After severe traumatic brain injury, adequate blood flow to the brain is essential for recovery. This depends on arterial blood pressure, yet intensive care units apply fixed targets to all patients - treating every brain and patient the same. This study aims to change that. With new technology, 'optimal' blood pressure can be determined for each individual brain and treatment can be tailored accordingly. This personalized approach to neurocritical care has never been tested in a randomized controlled study before. If effective in showing reduced brain damage biomarkers, it will fundamentally transform brain injury treatment and dramatically improve recovery outcomes for patients worldwide.

The long-term goal of the clinical trial is to develop effective, safe, and easily administered life-saving treatments for patients with moderate to severe traumatic brain injury (TBI). Patients with moderate to severe TBI will randomly receive either: 1. Standard of care treatment and normal saline 2. Standard of care treatment and one dose of valproic acid (VPA) at a lower dose or a higher dose

This study aims to develop and validate a prognostic model for neurocritical patients using multimodal brain monitoring data. By combining data from various monitoring techniques such as EEG, TCD, and NIRS, this model will help predict 90-day outcomes (awake, comatose, or deceased) and support personalized treatment decisions. The study is observational and involves no experimental interventions.

Narrative: Worldwide, traumatic brain injury (TBI) is a leading cause of death and disability among children and adolescents. The Investigators aim to test whether pediatric TBI treatment guided by invasive intracranial pressure monitoring produces better patient outcomes than care guided by a protocol without invasive monitoring. Study findings will inform clinical practice in treating pediatric severe TBI globally. Focused didactic and experience-based learning opportunities will increase the research capacity of pediatric intensivists in Latin America.

Context : Moderate to severe head trauma with altered state of consciousness is an extremely common pathology (between 60 and 120 cases per 100 000 people per year depending on the country and age group), and is responsible for 30% of deaths by trauma. It is complicated in 30-60% of cases by subarachnoid hemorrhage (SAH), which makes it the leading cause of SAH. SAH and its complications are well described when the origin is aneurysmal, notably cerebral vasospasm (CV) because it promotes delayed cerebral ischemia with a major prognostic impact. This is why the screening and prevention of this vasospasm are well established in the literature and in practice, in the nosological context of aneurysmal SAH. Research problem : However, when it comes to post-traumatic SAH, CV is a more maligned entity, with a much less detailed description. However, when we know the prognostic interest that it could have for patients, it seems legitimate to seek to define its physiopathological and epidemiological contours. On a prospective cohort of 290 subjects, Oertel et al. (2005) demonstrated, in head trauma patients, an incidence of approximately 40% of compatible signs with the recognized criteria of CV. To date, the literature remains sparse on this subject. Proposed study : In view of the incomplete scientific literature, the study team wish to carry out a prospective epidemiological study in moderate to severe head trauma patients complicated by SAH and hospitalized at the Martinique University Hospital, with the aim of better characterizing the incidence of the occurrence, and evolution of CV with clinical impact in these patients. One of the original aspects of the proposed study is the use of CT scan with perfusion sequence, which has shown its superiority to Transcranial Doppler. The other particularity is its prospective aspect and triggered by an alteration in the clinical state of the patient presenting a traumatic SAH, then directly linking the pathophysiology (cerebral ischemia) and the clinical impact. Thus, the diagnosis of traumatic CV will be made on a cerebral CT scan by the association of the 50% reduction in the caliber of one or more cerebral arteries and a perfusion defect in the perfusion sequence in a context of alteration of neurological clinical examination or deterioration of neurological monitoring parameters. Finally, few studies have monitored the evolution of these patients at 1 and 6 months after the initial event. Hypothesis : The research hypothesis is that in the population of moderate to severe head trauma patients hospitalized at the Martinique University Hospital, when a new neurological symptomatology or a deterioration in the state of consciousness occurs, it could be a post-truamatic CV in 15 to 20% of cases. Indeed, the rare studies find frequencies of radiologically confirmed CV in head trauma patients of around 30-45%, with low numbers of subjects, retrospective studies, or not correlated with the clinic and with the clinical and paraclinical data necessary for the positive diagnosis of this entity. The reported frequency of traumatic CV with clinical impact ranges between 15-20%. The study team therefore expect an incidence of 15 to 20% of CV with clinical impact in patients with traumatic SAH in Martinique. CV could be responsible for sudden deterioration of the neurological state in patients suffering from traumatic SAH between the 3rd and 12th day inclusive of treatment (according to retrospective studies already carried out) and responsible for its specific morbidity linked to cerebral ischemia localized in the spasmed area manifested by a worsening of the neurological prognosis on the modified Rankin scale.