Robot-assisted Training After Acquired Brain Injury and Disorders of Consciousness

To be deemed feasible, the inclusion rate must be 70% (12 out of 17 eligible patients), with a 95% confidence interval (CI) from 46.9% to 86.7%.

The data analyses are blinded by coding and blinding the groups (groups A and B) for the statistical analyses. After the analysis, two separate conclusions will be written before lifting the blinding and revealing the results.

To be deemed feasible, the ratio of completed sessions must be 80% (68 out of 85 sessions per group) with a 95% CI from 70.3% to 87.1%.

The data analyses are blinded by coding and blinding the groups (groups A and B) for the statistical analyses. After the analysis, two separate conclusions will be written before lifting the blinding and revealing the results.

Adverse events and reactions are recorded during, between and after interventions (days 1 to 26).

The DRS assesses the overall disability in patients with brain injuries in 8 functional areas in 4 categories. The scores range between 0 (no disability) to 29 (extreme vegetative state). A clinician performs the test, which requires no specific training, and takes about 15 minutes or can be done by interviewing staff or relatives. The assessment is blinded for allocation.

The CRS-R assesses the level of consciousness in patients with acquired brain injury and is used for monitoring the course of recovery. It consists of 6 subscales, and the scoring is based on specific behavioural responses to standardised sensory stimuli at the bedside. The minimum score is 0 (reflexive activity), and the maximum score is 23 (cognitively mediated behaviour). A trained clinician performs the test, which takes 15-30 minutes to administer. The CRS-R has a high sensitivity for detecting signs of consciousness and includes criteria for both minimally conscious state and emergence, plus and minus. A score of 10 or greater indicates a minimally conscious state or the emergence minimally conscious state. A trained neuropsychologist blinded for allocation performs the CRS-R.

The EFA assesses the functional status in the early stages of recovery after acquired brain injury. It comprises 20 items in 5 subscales rated on a 5-point ordinal scale. The minimum score is 20 (no function), and the maximum score is 100 (normal function). The EFA has been shown to have a ceiling effect with better functioning. The scoring is based on observations within the last 72 hours and takes 15-30 minutes to administer. The patient's team administers the EFA why assessment is not blinded to allocation.

The FIM assesses the severity of disability in rehabilitation patients and how much assistance is required for an individual to perform activities of daily living. It consists of 18 items (13 motor tasks and five cognitive tasks) rated on a 7-point ordinal scale. Scores range from 18 (totally dependent) to 126 (completely independent). The FIM has some floor effects in patients with low function. The scoring is based on observations within the last 72 hours and takes 15-30 minutes to perform the scale. The patient's team administers the FIM why assessment is not blinded to allocation.

The investigators explore if GAIT and STEP induce a cardiovascular response resembling physical activity, even though muscular activity might be absent. The percentage of heart rate max (HRmax) is used as an indicator of physical activity intensity.

HRmax is calculated from the following formulas:

Female: HRmax = 209.273 - 0.803 x age (R2 = 0.55) Male: HRmax = 208.609 - 0.716 x age (R2 = 0.47)

"Physical activity intensity" is reported using the following cut-offs for physical activity levels: Light intensity: < 65% of HRmax. Moderate intensity: 65-75% of HRmax. Vigorous intensity: 76-96% of HRmax.

In addition, the time (minutes) spent in light, moderate, or vigorous physical activity is explored.

The mean arterial pressure is, among others, regulated by the baroreceptors. It is explored how blood pressure regulates after GAIT and STEP. Continuous non-invasive arterial pressure (CNAP) and MAP are measured in a resting position before GAIT/STEP preparation. The investigators measure CNAP and MAP after the training session when the patient is positioned in a resting position (sitting or lying.)

The HRV is suggested to reflect responsiveness in patients with disorders of consciousness indirectly. HRV might reflect the interaction between the autonomic nervous system and cognitive, sensory, behavioural, and affective processes. The HRV is also an indirect measure of the sympathetic/parasympathetic balance. The HRV signal is obtained from the heart rate measures; the high frequency (HF) interval reflects parasympathetic activity (0.15-0.5Hz; HF); the low-frequency (LF) interval reflects mainly sympathetic but also parasympathetic activity (0.04-0.015 Hz; LF) and is typically correlated to physical stress; The LF/HF is classically considered an index of "sympathetic- vagal balance" of heart rate regulation, particularly during long-term recordings and is thus classically an expression of the baroreceptor feedback loop. It is expected that the interventions stimulate patient awakeness and awareness, which might be reflected in a change in HRV.

It is investigated if behavior differ between interventions. Behavior can be either random/not goal oriented, or a response/goal oriented to an input. This is evaluated from video recordings from the first and last session of each intervention where behavior like communication, visual awareness, and motor output are analysed.

Behavioural changes are explored from observations not blinded to allocation.