CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI

The PCL-5 is a self-report rating scale intended to assess 20 DSM-5 symptoms of Posttraumatic Stress Disorder. The standard recall period for the PCL-5 is one month. For CENTER-TBI a recall period of one week was used at the 2-3 week assessment, and the standard one month recall period was used at other time points. The sum of scores can range from 0 to 80, where high scores indicate more pronounced PTSD symptoms.

The Rivermead PCS Questionnaire (RPQ) was originally developed as a measure of severity of symptoms following MTBI. It consists of 16 post-concussion symptoms including headaches, dizziness, nausea/vomiting, noise sensitivity, sleep disturbance, fatigue, irritability, feeling depressed/tearful, feeling frustrated/ impatient, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision and restlessness. In the original version of the RPQ, participants are asked to rate the degree (on a scale of 0 to 4) to which a particular symptom has been absent or a mild, moderate or severe problem over the previous 7 days compared with premorbid levels. Total scores range from 0 to 64 with higher scores indicating more severe symptoms. Scores equal to or greater than 16 were considered indicative of persisting post-concussion symptoms.

The GOAT is a standardised assessment used to determine whether a participant is in post-traumatic amnesia (PTA). PTA is an early phase of TBI recovery during which the person with injury shows markedly impaired memory, confusion, fluctuation in performance, disorientation, and other neurobehavioral signs and symptoms. GOAT questions assess orientation, memory for the first event that the participant can recall after the injury, and memory for the last event that the participant can recall from before the injury.

The GOAT's total score must be achieved by subtracting from 100 the total amount of error scores (Total score = 100 - total amount of error scores). Scores lower than 75 point to the fact that the victim is still experiencing amnesia.

The Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal memory that assesses the ability to acquire 15 words. Recall is assessed after each presentation of the list, after the recall of an interference list, and again following a 20-minute delay. The total score for recall of the principal list ranges from 0 to 75, with higher scores indicating better performance.

Impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers.

In the timed up and go (TUG) test, subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again, for quantifying functional mobility. The presence of slowness, hesitancy, abnormal trunk or arm movements, staggering or stumbling is used to grade the patient from 1 (normal) to 5 (severely abnormal). Impaired mobility was defined as taking 14 seconds or longer to perform the TUG test.

The Coma Recovery Scale- Revised (CRS-R) is a standardized behavioral assessment instrument designed to measure neurobehavioral function in patients with disorders of consciousness (DOC). The CRS-R is comprised of six subscales addressing auditory, visual, motor, oromotor/verbal, communication and arousal functions. Subscale items are hierarchically-arranged, corresponding to brain stem, subcortical and cortically-mediated functions. Scores range between 0 (deep coma) and 23 (able to follow commands and to use objects purposefully). A total score less than 23 indicates impairment.

The Trail Making Test (TMT) is a measure of attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part B is similar except the person must alternate between numbers and letters and is more difficult and takes longer to complete. Both sections are timed and the score represents the amount of time required to complete the task, with shorter times indicating better performance. The maximum time allowed is 100 seconds.

Impairment cutoff: > 55.9 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

The TMT is a measure of attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part B is similar except the person must alternate between numbers and letters, is more difficult, takes longer to complete. Both sections are timed, the score represents the amount of time required to complete the task, with shorter times indicating better performance.

Impairment cutoff: > 143.7 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For CANTAB PAL, the individual must remember 1 to 8 patterns displayed in different positions on the screen. The score is the number of incorrect responses adjusted if necessary for trials that have not been completed. Scores ranged from 0-194 with lower score indicating better performance.

Impairment cutoff: > 72.3 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For CANTAB RTI, the individual must respond as quickly as possible to a circle presented at one of 5 positions. The outcome measure is the median time for correct responses (ms).

Impairment cutoff: > 470.9 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB SWM, the participant searches for tokens in boxes on the screen. The between errors measure is the number of times the participant queries a box that has already been searched. Errors ranged from 0 to 151, with lower numbers indicating better performance.

Impairment cutoff: > 52.0 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB RVP, sequences of numbers must be detected as they appear on the screen. The measure of accuracy is A' (A prime) which is derived from hits and correct rejections. The maximum score is 1 and, a higher A' indicates better performance.

Impairment cutoff: < 0.82 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB SOC, the individual moves circles to match a target in this task based on the Tower of Hanoi game. The score is the number of problems solved in the minimum number of moves, with a maximum of 12. Higher scores indicate better performance.

Impairment cutoff: < 5.7(based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB AST, participants respond either to the position of an arrow or the direction it is pointing, after being cued to the task on each trial. Total correct responses range from 0 to 160, where higher numbers indicate better performance.

Impairment cutoff: <135.5 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

A selected number of sites performed MRI follow up in a subset of patients that consented for imaging data collection. The CENTER-TBI MR protocols included a high-resolution 3D T1-weighted, a T2-weighted, a FLAIR, a DTI, a T2* sequence (gradient echo and/or SWI), and (optionally) a resting-state fMRI. Across all stratum the MRI sites performed a follow up MRI at 2-3 weeks after injury.

Traumatic Intracranial Abnormalities were assessed according to the TBI-Common Data Elements (CDEs). It indicates whether any of the 12 following imaging abnormalities are present (Mass lesion, Extra-axial Hematoma, Epidural Hematoma, Subdural Hematoma Acute, Subdural Hematoma Subacute Chronic, Subdural Collection Mixed Density, Contusion, TAI, traumatic Subarachnoid Hemorrhage, Intraventricular Hemorrhage, Midline Shift or Cisternal Compression.