Traumatic Brain Injury (TBI) Patients

The purpose of this research study is to investigate the effects of a home-based 3-month long walking exercise program on cognitive (thinking) performance in persons with TBI. As a participant, you will complete this 3-month exercise program now or after a 3-month wait period.

The two goals of the proposed study are: (1) To determine how brain activity changes with cognitive recovery over time from acute to chronic phases of traumatic brain injury (TBI). (2) To determine how the time of anodal transcranial electrical stimulation (A-tES) administration affects cognitive performance and brain activity in TBI. To achieve these study goals, the investigators will conduct a pilot clinical trial over three years in which the investigators aim to recruit 60 patients with moderate to severe TBI at the University of Cincinnati Medical Center (UCMC). During the acute phase of TBI, all participants will complete clinical questionnaires and perform 2 cognitive computer tasks while their brain activity is recorded. Half of the participants will be randomly selected to receive A-tES for 15 minutes while performing cognitive tasks and the other half will receive sham stimulation. All participants will be followed for 6 months. During their 3-month follow-up, the investigators will perform another session where all participants complete the questionnaires and receive A-tES while performing cognitive tasks during brain recording. In their last visit at 6 months post-injury, all participants will complete the questionnaires and cognitive tasks with brain recording but no stimulation treatment. From the collected data, the investigators will determine if time from brain injury correlates with brain activity during performance of cognitive tasks. The investigators will also assess the efficacy of early A-tES treatment for improving cognitive task performance and clinical test ratings at 6 months post-injury in comparison to A-tES delivered during the 3-month follow-up visit.

Many people develop intolerance to light after a head injury, leading to ambient light levels causing discomfort. We do not fully understand why this occurs and how it should be treated. A growing number of clinicians have reported improvement in TBI related symptoms reported by patients that undergo daily fixation training with a dim light target. While fixation training using various colored light targets is reported, blue light targets specifically appear to be used in this patient population more often than other light target colors. However, the effectiveness of this approach has yet to be assessed in a well-controlled clinical study. In this work, we will recruit individuals who had a recent brain injury and developed increased light sensitivity. Participants will be divided into two groups: one that first uses daily 20 minute sessions for 12 weeks with the at-home fixation device set to display a blue light target; and another that will undergo similar sessions for 12 weeks using a red light target. Every 6 weeks, masked examiners will measure how well participants can read letters on an eye chart, record pupil responses to light, measure the side vision, measure eye alignment and focusing ability when viewing a near target, and collect information about participants' symptoms. In a cross-over study design, the participants will then switch to sessions involving the other colored fixation light target for another 12 weeks, with data being again collected every 6 weeks. Potential differences in pupil responses to light between the treatment groups will be assessed as an objective outcome measure and compared to subjective symptom survey information. Thus, this work will test the hypothesis that daily fixation training using a blue light target can alleviate light intolerance in participants after head injury more than fixation training with a red light target, and this improvement is associated with altered pupil responses to light. As a significant minority of eye care clinicians currently utilize this approach in this population of patients, this study has the potential to influence clinical practice patterns whether the fixation training is shown to be effective or not.

This study is a Phase II, randomized, quadruple-blinded, placebo-controlled clinical trial designed to test whether vitamin D₃ supplementation can improve recovery after mild-to-moderate traumatic brain injury (TBI) in adults. Traumatic brain injury often leads to inflammation and poor neurological outcomes, and many patients are vitamin D-deficient. Vitamin D₃ is a safe, widely available supplement that may reduce inflammation and support brain recovery. A total of 240 adults (18-65 years) with mild-to-moderate TBI will be enrolled at Lagos State University Teaching Hospital, Nigeria. Participants will be assigned to one of four groups: Group A (Deficient + High-Dose D₃): 40,000 IU loading dose, then 4,000 IU daily for 3 weeks Group B (Deficient + Standard-Dose D₃): 2,000 IU daily for 3 weeks Group C (Sufficient + Standard-Dose D₃): 2,000 IU daily for 3 weeks Group D (Sufficient + Placebo): placebo daily for 3 weeks All groups will be followed for 24 weeks. Blood tests at baseline, week 1, week 2, and week 4 will measure inflammation. Neurological recovery will be assessed at weeks 4, 12, and 24 using the Glasgow Outcome Scale-Extended (GOS-E) and Modified Rankin Scale (mRS). The main outcomes are changes in inflammatory markers. Secondary outcomes include mortality, functional recovery, hospital stay, safety, and cost-effectiveness. The results may identify a low-cost, scalable treatment to improve outcomes after TBI, especially in low-resource settings.

Patients that undergo decompressive craniectomy are at risk of delayed changes in brain function known as "Sunken Flap Syndrome" or "Syndrome of the Trephined." The goal of this clinical trial is to see if placing a prosthetic over patients' skull defects can prevent "Sunken Flap Syndrome." The main questions are: 1. Can placing a prosthetic device over patients' skull defects prevent Sunken Flap Syndrome? 2. Can placing a prosthetic device over patients' skull defects decrease healthcare costs? 3. Can placing a prosthetic device over patients' skull defects improve recovery and return of brain function after decompressive craniectomy? Patients that experience traumatic brain injuries, brain bleeds, and large strokes can build up high levels of pressure in the skull. When this pressure can't be controlled with medications, a life-saving surgery called a decompressive hemicraniectomy (DC) is often performed. In this surgery, a large portion of the patient's skull is removed to decrease pressure on the brain and decrease permanent damage. After this surgery, many patients experience sinking of the brain in the skull as the pressure inside the head improves. The skull normally protects the brain from the outside environment. When large parts of the skull are removed, the brain is not able to regulate itself normally. This can lead to a number of problems, such as headaches, weakness, seizures, and even coma and permanent brain damage. This is referred to as "Sunken Flap Syndrome" (SFS) or "Syndrome of the Trephined" (SoT). After 3-6 months, patients can have the missing skull surgically repaired, which improves and sometimes fixes SFS, but the damage is sometimes too severe to be reversed. There are reports of patients with SFS treated with custom-made prosthetics that cover the missing piece of skull. In this study, the researchers want to see if wearing a custom-made prosthetic can prevent patients from experiencing SFS. Patients will also receive additional non-invasive measurement to see if the prosthetic can improve brain function and recovery. Finally, the researchers want to know if the prosthetic is cost-effective by decreasing the frequency that patients see doctors or receive care to treat SFS. Patients or the patient's medical decision makers will be asked if the patient wants to participate in the study after DC. If the patient or decision maker agrees to participate, the patient will be also asked if the patient wants to wear the prosthetic. The prosthetic is made of a common material used in other facial prosthetics. Patients that agree to wear the prosthetic will have a custom plate made for the participant. All patients will receive the same post-operative care and appointments whether or not the prosthetic is worn. The participant will go to the normally scheduled post-operative doctor's appointments at 2 and 4 weeks after initial DC surgery. Patient's that agree to wear the prosthetic will receive it at the 4-week post-DC appointment. The participant will then be asked to wear it as much as possible, but to let the researchers know if the participant experiences any pain, itching, discomfort or other problems. All patients will also be seen by the patient's physician before and after and after skull repair. At all appointments, patients will receive non-invasive testing of brain function. Recovery and rate of SFS will be compared between patients that do and do not wear the prosthetic. Participants will: * Go to the normally scheduled 2 and 4 week post-DC appointments * Go to the normally scheduled pre- and post-skull repair appointments * Receive additional non-invasive brain health testing at each appointment Participants that agree to wear a prosthetic will: * Receive the custom prosthetic at the 4-week post-DC appointment * Wear the prosthetic as much as possible, including at night * Take a brief survey about the prosthetic at the post-skull repair appointment

This clinical trial aims to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive brain stimulation method, can improve attention and memory in veterans with traumatic brain injury (TBI) and depression and/or posttraumatic stress disorder (PTSD). The study seeks to answer two main questions: 1. Can active taVNS improve attention and memory compared to sham (placebo) stimulation? 2. Does taVNS affect heart rate variability (HRV)? taVNS delivers a gentle electrical current to the vagus nerve through electrodes placed on the ear, targeting brain areas involved in attention and memory without requiring surgery. This study uses a crossover design, meaning all participants will experience two sessions: one with active taVNS and one with sham stimulation. The sham session feels similar but does not deliver actual stimulation, allowing researchers to compare the two and understand taVNS's effects on the brain. In a single visit, participants will: * Complete eligibility screening (questionnaires and vital signs). * Undergo two sessions (one active and one sham), randomly assigned. * Perform attention tasks before and after each session. * Have their heart rate monitored during the sessions. The findings will help determine whether taVNS could be an effective treatment for improving attention and memory in veterans with TBI.

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.

Each year, approximately 69 million people worldwide suffer from traumatic brain injuries (TBI), representing a significant burden on public health, society, and the economy. Timely and accurate care can influence short-, medium-, and long-term outcomes, making the reduction of diagnostic delays crucial. TBI diagnostics require careful consideration, as initial evaluations may differ from final assessments, and patient conditions may evolve over time. In this monocentric, observational, post-market follow-up study we aim to evaluate the Abbott i-STAT™ TBI Plasma Test in detecting circulating brain biomarkers (GFAP and UCH-L1) in adult patients with TBI. The study involves recruiting 200 adult patients (aged 18-65 years) presenting to the emergency department with TBI over a two-year period. For each participant, a blood sample will be collected as part of routine clinical care and analyzed using the Abbott i-STAT™ TBI Plasma Test within 12 hours of the trauma. The results will be compared with those obtained from cranial CT scans, the gold standard for diagnosing intracranial injuries. Specifically, the study aims to assess the diagnostic accuracy of the test in excluding intracranial injuries, particularly in cases of mild TBI, and to explore potential correlations between biomarker presence and injury severity. No additional procedures beyond routine clinical care are required, and all collected data will be used exclusively for the study's predefined objectives.

Accurate and non-invasive methods for objectively identifying and monitoring head injuries (such as a concussion) are still an unmet need. It is known that pupil constriction in response to light stimuli can reflect changes in neural activity in the brain and is associated with sleep disturbances. The investigators aim to examine the feasibility of using virtual reality goggles for monitoring traumatic brain injury by analyzing the pupillary response to multifocal chromatic stimuli. The VR device was programmed to present brief, low-intensity light stimuli (without glare), while the headset's camera records the pupil's reaction.

This prospective observational study evaluates the safety profile and patient-reported outcomes associated with MUSE (Multilineage-differentiating Stress-Enduring) stem cell therapy in individuals aged 6 to 75 with chronic traumatic brain injury (TBI). Participants independently elect to receive MUSE cell treatment through international clinical programs, and this study aims to capture real-world evidence on the potential therapeutic effects and risks of this emerging regenerative approach. The study does not administer any intervention. Instead, it follows participants who have received, or plan to receive, MUSE cell infusions outside the United States. Over a 12-month follow-up period, data will be collected on neurological functioning, quality of life, activities of daily living, and any reported adverse events or complications. Information will be gathered through remote interviews, structured digital surveys, and review of medical documentation when available. This research is sponsored by Healing Hope International and is intended to contribute to the ethical and responsible advancement of novel cell-based therapies by generating real-world evidence that may guide future clinical trial development and inform patient care practices.

The goal of this study is to learn if a enhanced environment (Metro Café) with multi model approach (an approach that combines several therapies) in chronic traumatic brain injury improves outcomes of recovery better than traditional therapy. The main questions it aims to answer are: * Determine the amount of therapy dosage (speech, cognition, arm and leg movements) obtained during the Metro Café therapy session. * Evaluate the connection between environmental enrichment dosage (the Metro Café) and clinical outcome scores. Researchers will compare Metro Café Treatment to those who do not receive this treatment to see if better improvements in function after a traumatic brain injury are seen in the Metro Café Treatment Participants will train in the Metro Cafe during the 2-month gap between assessments, for a total of 18 training sessions, each up to 2 hours, 3 times per week. Participants will greet and serve customers drinks and snacks, maintain food supplies at the counters and performs housekeeping tasks with advice and assistance from a supervising researcher as needed,

Traumatic Brain Injury (TBI) is a significant cause of mortality and morbidity worldwide. However, the literature on determining its severity and predicting prognosis is insufficient. This study aimed to examine the differences in metabolite levels between trauma patients with severe TBI and orthopedic trauma patients without brain injury.

The goal of this observational study is to evaluate the diagnostic accuracy of non-invasive intracranial pressure (ICP) and intracranial compliance (ICC) pulse morphology and associated parameters (such as the P2/P1 ratio and nTTP) obtained with the brain4care system for the screening of intracranial hypertension (ICH) in patients with traumatic brain injury (TBI) and stroke treated in Brazil's public health system (SUS). The main questions it aims to answer are: Can non-invasive ICP and ICC pulse morphology reliably identify or exclude intracranial hypertension, cerebral edema, and hemorrhage compared to CT findings and clinical/neurological evaluations? Can this approach differentiate ischemic stroke from hemorrhagic stroke with sufficient accuracy? Does the use of brain4care contribute to earlier detection, improved clinical decision-making, and cost reduction in emergency settings?

The goal of this clinical trial is to determine which crystalloid (saline or balanced) should be used in the critical management of Traumatic Brain Injury (TBI) in moderate or severe TBI patients. This trial will determine whether the use of saline or balanced crystalloids is associated with improved outcomes in TBI patients. Participants will 1. be given fluids through the veins, either saline or balanced fluid will be given. 2. From the first day to the day 14 of the hospitalization (or discharge, whichever comes first), vital signs, laboratory values, treatments given, and other medical data will be collected from the medical record. 3. Six months later, your final disability, if any, will be assessed during your follow-up with a doctor. It involves answering a short survey that will take about 5 minutes or less.

Rationale/gaps in existing knowledge: The prophylaxis for post-traumatic seizures (PTS) remains controversial due to a lack of class I evidence. Investigators plan to conduct a high-quality, prospective, multicentric, randomized study regarding seizure prophylaxis in traumatic brain injury (TBI) with phenytoin, levetiracetam, and the placebo in three respective treatment groups, along with the effect of drug polymorphism on seizure occurrence. Novelty: Literature is scarce regarding the ideal management of early PTS in traumatic brain injury (TBI), a major public health problem. Further, no study has evaluated the effect of genetic polymorphism on seizure occurrence in traumatic brain injury. This Multicentric study will be the first of its kind, not only in India but also globally. Objectives: To evaluate the seizure incidence \& efficacy of the respective anti-epileptic drug in each treatment arm. Assessment of clinical \& functional outcomes, safety profile, and cost-effectiveness in each group. Effect of genetic polymorphisms on seizure incidence among study participants Methods: A Multicentric prospective randomized placebo-controlled double-blinded clinical trial is planned. After satisfying eligibility criteria and informed consent, TBI patients will be randomly allocated into three arms 'phenytoin arm', 'levetiracetam arm', and 'placebo'. Drug polymorphism will be analyzed in all the patients using quantitative real-time PCR. Expected outcome: This study will provide high-quality evidence in PTS management and will establish the role of prophylactic anti-epileptics in PTS. This study also opens the plethora of undesignated roles of genetic polymorphism in the efficacy and safety of levetiracetam and phenytoin in traumatic brain injury patients.

The role of nonselective beta adrenergic blocker as antistress agent in severe traumatic brain injury