Home-Based Exergame Motor-Cognitive Rehabilitation for Traumatic Brain Injury

Traumatic brain injury (TBI) is one of the leading causes of disability among young adults and is associated with a substantial economic burden on healthcare systems, as well as on patients and their families.

TBI may result in cognitive impairments, including deficits in attention, memory, and executive functions, as well as behavioral disturbances such as apathy, anxiety, and depression. In a smaller proportion of cases, motor dysfunctions, including gait and balance impairments, may also occur. These deficits negatively affect patients' independence and social participation and may also reduce caregivers' quality of life.

Conventional rehabilitation for individuals with TBI typically relies on multidisciplinary interventions, including cognitive training, physiotherapy, and occupational therapy. Although these approaches may improve specific functional domains, evidence supporting their effectiveness in enhancing overall independence and social participation remains limited. Therefore, there is a need to develop more targeted and personalized neurorehabilitation programs based on clinical, instrumental, and biological biomarkers, while ensuring continuity of care through integrated hospital-to-home rehabilitation pathways.

In the post-discharge setting, combined cognitive-motor rehabilitation has gained increasing attention due to the close interaction between motor and cognitive functions in everyday activities. In particular, telerehabilitation delivered through virtual reality-based exergames has shown promising results in improving mobility, cognitive performance, and functional independence in individuals with TBI. Compared with traditional face-to-face rehabilitation, which typically requires one-to-one therapist supervision, telerehabilitation enables patients to perform training at home through synchronous, asynchronous, or hybrid modalities, providing a more flexible and efficient model of care while reducing travel requirements and waiting times for rehabilitation services.

In light of the above, this pilot controlled, non-randomized, single-blind (assessor-blinded) clinical trial aims to investigate the effectiveness of home-based cognitive-motor telerehabilitation as a post-discharge continuity-of-care intervention compared with standard outpatient rehabilitation in individuals with traumatic brain injury (TBI) following discharge from intensive inpatient neurorehabilitation. We hypothesize that participants receiving the experimental intervention will demonstrate greater or at least comparable improvements in functional independence, cognitive performance, mobility, and quality of life than those receiving conventional outpatient rehabilitation, while also reducing caregiver burden.

• HOME-EXER telerehabilitation protocol (Other): Participants will follow the HOME-EXER telerehabilitation protocol
• OUT-REHAB rehabilitation protocol (Other): Participants will follow the OUT-REHAB rehabilitation protocol

Primary outcomes

• Disability Rating Scale (DRS) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0)]: The Disability Rating Scale (DRS) is a validated measure of global functional disability after traumatic brain injury. It assesses impairment, disability, and participation restrictions across domains of consciousness, self-care, dependence, and psychosocial functioning. Scores range from 0 to 29, with higher scores indicating greater disability.

Secondary outcomes

• Montreal Cognitive Assessment (MoCA) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated screening tool used to assess global cognitive functioning. Total scores range from 0 to 30, with higher scores indicating better cognitive performance.
• Symbol Digit Modalities Test (SDMT) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated neuropsychological test used to assess information processing speed, attention, and visual scanning. Participants are required to match symbols with corresponding numbers according to a reference key within 90 seconds. The score consists of the number of correct symbol-digit pairings completed in 90 seconds, with higher scores indicating better cognitive performance and faster processing speed.
• California Verbal Learning Test II (CVLT-II) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated neuropsychological test used to assess verbal learning and memory. A list of words is read aloud over five consecutive trials, and after each presentation participants are asked to freely recall as many words as possible. The score consists of the total number of correctly recalled words across the five learning trials, with higher scores indicating better verbal learning and memory performance.
• Brief Visuospatial Memory Test - Revised (BVMT-R) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated neuropsychological test used to assess visuospatial learning and memory. Participants are shown a display containing six geometric figures for 10 seconds and are then asked to reproduce them from memory. This procedure is repeated over three learning trials. The score consists of the total number of points obtained across the three recall trials, based on the accuracy and location of the reproduced figures, with higher scores indicating better visuospatial learning and memory performance.
• Hospital Anxiety and Depression Scale (HADS) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated self-report questionnaire used to assess symptoms of anxiety and depression in medical and rehabilitation settings. The scale consists of 14 items, divided into two subscales: HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D), each comprising 7 items. Scores for each subscale range from 0 to 21, with higher scores indicating greater levels of anxiety or depressive symptoms. The total HADS score ranges from 0 to 42.
• Berg Balance Scale (BBS) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated clinical scale used to assess functional balance. The assessment consists of 14 functional tasks involving sitting, standing, transfers, reaching, turning, and single-leg stance. Each item is scored from 0 to 4, with a total score ranging from 0 to 56. Higher scores indicate better balance performance. Kinematic data will be recorded by an inertial sensor on lower back.
• Six-Minute Walk Test (6MWT) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated test used to assess walking capacity and endurance. Participants are instructed to walk as far as possible along a 30-meter corridor for 6 minutes, with rest periods and walking aids allowed if necessary. The outcome measure is the total distance walked in 6 minutes, with greater distances indicating better walking capacity and endurance. Kinematic data will be recorded by three inertial sensors on lower back and feet.
• Timed Up and Go (TUG) Test [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated measure of functional mobility and dynamic balance that assesses the time required for a participant to stand up from a chair, walk 3 meters, turn around, walk back, and sit down. The test is administered under both single-task and cognitive dual-task conditions. In the dual-task condition (TUG-DT), participants perform the TUG while simultaneously completing a cognitive task consisting of generating alternating letters of the alphabet during walking. Outcome measures include completion time (seconds), and the Dual-Task Cost (DTC) for motor and cognitive performance, calculated as the percentage change between single-task and dual-task conditions. Lower completion times and lower DTC values indicate better functional mobility and dual-task ability. Kinematic data will be recorded by an inertial sensor on lower back.
• EuroQol 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated self-report measure of health-related quality of life, used for clinical and economic appraisal. The questionnaire assesses five dimensions of health status: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated on five levels of severity ranging from no problems to extreme problems. Responses are converted into a health utility index score, with higher scores indicating better perceived health status. The instrument also includes a Visual Analogue Scale (EQ VAS) ranging from 0 (worst imaginable health) to 100 (best imaginable health), on which participants rate their overall health.
• Quality Of Life After Brain Injury (QOLIBRI) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated, disease-specific self-report questionnaire designed to assess health-related quality of life in individuals with traumatic brain injury (TBI). The instrument evaluates six domains: cognition, self, daily life and autonomy, social relationships, emotions, and physical problems. Items are rated on a 5-point scale, and responses are combined to generate a total score ranging from 0 to 100, with higher scores indicating better perceived quality of life after brain injury.
• Community Integration Questionnaire (CIQ) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: A validated questionnaire used to assess community integration following acquired brain injury. The instrument evaluates participation in three domains: home integration, social integration, and productive activities (e.g., work, education, or volunteering). Scores from individual items are summed to generate a total score, typically ranging from 0 to 29, with higher scores indicating greater independence and community participation.
• Caregiver Burden Inventory (CBI) [T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0).]: Caregiver Burden Inventory (CBI): A validated self-report questionnaire used to assess the multidimensional burden experienced by caregivers. The instrument consists of 24 items grouped into five domains: time-dependence burden, developmental burden, physical burden, social burden, and emotional burden. Each item is rated on a 5-point scale (0-4), yielding a total score ranging from 0 to 96, with higher scores indicating greater caregiver burden. The CBI is widely used to evaluate the impact of caregiving responsibilities on caregivers' well-being and daily functioning.
• Adverse events [From T0 (hospital discharge, pre-intervention) to T2 (follow-up, 6 months after T0).]: Organized reporting of adverse events occurring during the study

Other outcomes

• Sex Data [T0 (hospital discharge, pre-intervention)]: Sex of participants, as reported in the medical record.
• Age Data [T0 (hospital discharge, pre-intervention)]: Age of participants
• Body Height [Participant's body height measured in centimeters (cm)]: Participant's body height measured in centimeters (cm)
• Body Weight [T0 (hospital discharge, pre-intervention)]: Participant's body weight measured in kilograms (kg)
• Years of education [T0 (hospital discharge, pre-intervention)]: Number of years of formal education completed by the participant
• Treatment adherence [T1 (post-intervention, 7 weeks after T0),]: Percentage of completed rehabilitation sessions/hours relative to the total number of sessions/hours scheduled during the intervention period.
• Dropout rate [T2 (follow-up, 6 months after T0)]: The proportion of participants who discontinue the study intervention or withdraw from the study before completing the scheduled treatment and/or follow-up assessments, expressed as a percentage of the total enrolled participants.
• System Usability Scale (SUS) [T1 (post-intervention, 7 weeks after T0)]: A validated self-report questionnaire used to assess the usability of a technological system. The SUS consists of 10 items rated on a 5-point Likert scale ranging from strongly disagree to strongly agree. Responses are converted into a total score ranging from 0 to 100, with higher scores indicating greater perceived usability of the system. The questionnaire is administered only to participants in the experimental group.
• Service User Technology Acceptability Questionnaire (SUTAQ) [T1 (post-intervention, 7 weeks after T0)]: A validated questionnaire used to assess participants' acceptance and perceived value of telehealth technologies. The SUTAQ evaluates multiple dimensions of technology acceptance, including perceived benefits, privacy and discomfort, satisfaction, accessibility, and concerns regarding the use of the technology. Items are rated on a Likert scale, with higher scores reflecting greater acceptability and satisfaction with the telerehabilitation service. The questionnaire is administered only to participants in the experimental group.
• Healthcare Resource Utilization and Caregiver Time Costs [From T0 (hospital discharge, pre-intervention) to T1 (post-intervention, 7 weeks after T0).]: Structured questionnaire to collect data about additional rehabilitation treatments, specialist medical visits and instrumental examinations, distance traveled to healthcare facilities, transportation modalities, time spent and work hours lost by patients and/or caregivers to attend healthcare services, participation in sports or recreational activities and related costs, time spent by informal caregivers providing assistance, use of paid caregiving services, assistive devices and their procurement modalities, and concomitant medications.

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

TBI patients Inclusion Criteria

* Discharge from intensive inpatient post-acute rehabilitation following a first traumatic brain injury (TBI).
* Level of Cognitive Functioning Scale (LCF) score ≥ 6, indicating appropriate and goal-directed cognitive responses.
* Ability to walk at least 30 meters, with or without an assistive device.
* Ability to maintain an unsupported standing position for at least 3 minutes.
* Provision of written informed consent.

TBI patients Exclusion Criteria

* Diagnosis or suspected diagnosis of a neurodegenerative disorder.
* Previous history of traumatic brain injury.
* History of major psychiatric disorders (e.g., schizophrenia or bipolar disorder), primary sleep disorders, or epilepsy.
* Severe visual or auditory impairment that could interfere with study assessments or participation in the rehabilitation program.
* Severe expressive and/or receptive aphasia.
* Language barriers preventing reliable cognitive assessment or informed consent procedures.
* Current pregnancy.

Healthy Subjects - Exclusion Criteria

* Presence of any neurological, sensrory, cognitive, psychiatric, cardiopulmonary, or musculoskeletal condition that may affect study participation or outcome measures
* Language barriers preventing reliable cognitive assessment or informed consent procedures.
* Current pregnancy.

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