Participants

A consecutive series of patients was recruited prospectively from the two Level-I trauma centers in the greater Houston, Texas metropolitan area. Inclusion criteria included patients aged 18-50 years at the time of injury who presented to, and were treated and released from, the Emergency Department (ED) less than 24 hours following an injury to the head or extremities. Patients were fluent in either English or Spanish. Specific inclusion criteria for patients with mTBI included a documented/verified head injury, Glasgow Coma Scale (GCS)(15) score of 13-15, loss of consciousness < 30 minutes, posttraumatic amnesia (PTA) < 24 hours, and no trauma-related abnormalities on emergent CT scan. Patients with mTBI were assessed with the Galveston Orientation and Amnesia Test (GOAT)(16) to determine if they were in PTA (GOAT score < 75) at the time of study consent. If so, a legally authorized representative would be approached to provide consent; however, no enrolled subjects met this criterion, and all were enrolled with self-consent. The definition of mTBI used in this study followed the guidelines of the Department of Defense(17) and the American Congress of Rehabilitation Medicine(18). All enrolled participants with mTBI had visible evidence of head trauma associated with multiple mechanisms, in the form of bruising/contusions/abrasions to the head, scalp, or face (84%) and scalp lacerations (44%), of which 54% (24/44) required sutures. Participants were excluded from the study for the following criteria: previous head injury requiring hospitalization (including treatment and discharge from an ED), Abbreviated Injury Scale (AIS)(19) score > 3 for any single body region, significant history of pre-existing serious mental disorders (e.g., psychotic disorder, bipolar disorder, or preinjury PTSD formally diagnosed by psychiatrist/psychologist), Alcohol Use Disorders Identification Test (AUDIT)(20,21) score > 8, Drug Abuse Screening Test (DAST-10)(22-24) score > 3, blood alcohol level >80 mg/dL (or other ED chart documentation of clinical intoxication) at the time of informed consent, left-hand dominant (due to neuroimaging requirements of the larger study), presence of contraindications for magnetic resonance imaging (MRI; e.g., shrapnel, ferrous metal implants, pacemaker, claustrophobia, etc.), or a positive urine pregnancy test.

Study sample

A total of 101 participants with mild TBI were enrolled in the study (see Table 1). As expected, mechanisms of injury in the mTBI group most frequently included motor vehicle crash (MVC; 37.7%) or fall (20.7%). To facilitate inter-study comparisons, the Injury Severity Score (ISS)(19) was reported both with and without the head region as it inflates the ISS for the mTBI group due to coding for concussion.

Measures

Diagnostic and Statistical Manual, 4th Edition (DSMIV): The DSM-IV(9) proposed criteria for PCD include: (A) history of TBI causing “significant cerebral concussion;” (B) cognitive impairment in attention or memory; (C) at least three of eight symptoms (fatigue, sleep disturbance, headache, dizziness, irritability, affective disturbance, personality change, apathy) appearing shortly after injury and persisting for at least 3 months; (D) symptoms beginning after injury or representing a significant worsening of pre-existing symptoms; (E) interference with social and/or occupational functioning; and (F) exclusion of dementia due to head trauma (code 294.1) and other disorders that better account for the reported symptoms. Criteria C and D set a symptom threshold such that symptom onset or worsening must be contiguous to the injury, are distinguishable from pre-existing symptoms, and have a defined minimum duration. DSM-IV criterion A (history of TBI) was determined by the emergency department (ED) trauma physicians, and criterion F (exclusion) was assumed to have been met because of the study’s inclusion/exclusion criteria. Having satisfied criteria A and F, the diagnosis of PCD under DSM-IV was made if the participant’s interview responses satisfied criteria C (symptoms), D (symptom threshold), and E (clinical significance) and if at least one of the participant’s neuropsychological test scores suggested impairment (Criterion B). A neuropsychological impairment of attention or memory was operationally defined as one or more scores of the study’s three measures (two variables each) of attention and memory including: Symbol-Digit Modalities Test (SDMT; written or oral scores), Verbal Selective Reminding Test (VSRT; consistent long-term retrieval and delayed recall), or the Brief Visuospatial Memory Test-Revised (BVMT-R; total recall across three trials and delayed recall) falling 1.5 or more standard deviations away from the mean in the direction of impairment based on published normative data. The DSM-IV criteria were used in this study as the DSM-5 was not yet published when the 5-year study began.

International Classification of Disease, 10th Edition (ICD-10): The ICD-10 includes both clinical and research criteria for PCS. The World Health Organization has published two diagnostic criteria sets for PCS: clinical criteria(10) and research criteria(11). In the notes for users in the research criteria (pages 1-4), the authors state that the research criteria“ …provides specific criteria for the diagnoses contained in Clinical descriptions and diagnostic guidelines.” The ICD-10 clinical criteria require a history of TBI”… usually sufficiently severe to result in loss of consciousness,” three or more of the following eight symptoms must be present (headache, dizziness, fatigue, irritability, insomnia, concentration or memory difficulty, and intolerance of stress, emotion, or alcohol), and the cognitive and other complaints are”… not necessarily associated with compensation motives.” The criteria also state that at least three of the set of required complaints must be present to make a definite diagnosis. Additionally, the guidelines indicate that the symptoms may be accompanied by depression or anxiety resulting from some loss of self-esteem fear of permanent brain damage; these symptoms are not apparently required, however. The diagnosis of PCS under the ICD-10 clinical criteria was made if the participant’s interview responses indicated that three or more of the symptoms listed had been present for at least 1-week postinjury (operationally defined in the absence of a required duration defined by the ICD-10 clinical criteria) and there was no evidence of suboptimal performance on a measure of performance validity. Patients were considered to have met the TBI criterion (determined by the ED trauma physicians) but were not required to have had a documented loss of consciousness (LOC) as the majority of participants in our sample were injured in the absence of a reliable witness and/or were unreliable historians for this information.

The ICD-10 research criteria require history of head trauma resulting in LOC preceding the onset of symptoms by no longer than four weeks. At least three or more of the following 12 symptoms must be present (headache, dizziness, fatigue, noise intolerance, irritability, emotional lability, depression and/or anxiety, subjective complainants of difficulty in concentration and memory problems (without clear objective evidence from psychological tests), insomnia, reduced tolerance to alcohol, and preoccupation with the previous symptoms and fear of permanent brain damage (even hypochondriacal) with the adoption of a sick role. To our knowledge, this criteria set has not previously been used in any published studies. The diagnosis of PCS under the ICD-10 research criteria was made if the participant’s interview responses indicated that three or more of the symptoms listed had been present for at least 1-week postinjury (operationally defined in the absence of a required duration defined by the ICD-10 research criteria). Participants were considered to have met the TBI criterion (determined by the ED trauma physicians).

Connor-Davidson Resilience Scale (CD-RISC): The CD-RISC(25) is a 25-item self-report of psychological resilience with a reported factor structure including constructs of personal competence/tenacity, tolerance of negative affect/stress, positive acceptance of change, internal locus of control, and spirituality. Items are rated using a 5-point Likert scale ranging from 0 – ‘not true at all’ to 4 – ‘true nearly all of the time.’ The total score was used as the primary variable in this study.

Center for Epidemiologic Studies Depression Scale (CES-D): The CES-D(26) is a 20-item self-report measure of depressive symptom severity rated on a 4-point Likert scale (0 – ‘rarely or none of the time’ to 3 – ‘most or all of the time’). Confirmatory factor analysis has demonstrated a factor structure similar to that of the general population (e.g., depressed affect, positive affect, somatic/reduced activity, and interpersonal relationships) in patients with mild to moderate TBI(27). The total score was used as the primary variable in this study.

Rivermead Post Concussion Symptoms Questionnaire (RPCSQ): The RPCSQ(28-30) is a 16-item self-report of cognitive, emotional, and somatic complaints commonly reported following mTBI. Factor analyses have revealed three factors including cognitive, somatic, and emotional problems(30), although differing factor structures also have been reported.(31) The participants rated the severity of each symptom (current experience compared to preinjury levels) from 0 – ‘not experienced at all’ to 4 – ‘severe problem.’ The onset/duration of each symptom was also recorded. The total score was used as the primary variable in this study.

Brief Visuospatial Memory Test-Revised (BVMT-R): The BVMT-R(32) is a measure of visuospatial learning and memory. Participants are shown design stimuli in a 2×3 array for 10 seconds and are asked to draw as many of the figures as they can in the correct location. This procedure is used for three learning trials. The participants are again asked to draw these figures following a 25-minute delay. The primary variables included the total recall across three trials, and the delayed recall score. Scores were standardized using the BVMT-R scoring software and normative data.

Symbol-Digit Modalities Test: The SDMT(33) is a timed, code substitution task that has demonstrated excellent sensitivity in detecting processing speed deficits secondary to cerebral dysfunction assessing the domains of sustained attention and working memory. Using a reference key, the participant is asked to pair numbers associated with simple geometric figures under time constraints. In the written format, the participant writes the correct number below each geometric figure. In the oral format that follows, the participant verbally produces the correct number associated with each figure and the examiner records these responses. The total numbers of correct responses for written and oral versions are the primary variables. Normative data were obtained from the SDMT manual.

SF-12: The 12-item Short Form Survey (SF-12)(34) is a brief measure of physical and psychological well-being that was derived from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)(35). It has demonstrated reliability and validity in clinical and population-based studies in the U.S.(34,36) and the short form was found to function as well as the longer SF-36 in longitudinal studies(36). The Mental and Physical Component Summary scores were the primary variables using the normative data provided by the publisher.

Verbal Selective Reminding Test (VSRT): The VSRT(37,38) is a multi-trial measure of verbal learning in which a list of 12 semantically-unrelated words is initially presented. On subsequent trials, only those words not recalled in the previous recall trial are presented until the participant either recalls all 12 words on two consecutive trials, or until all learning trials are exhausted. The six-trial version of the VSRT was used in this study. The primary outcome measures used consistent long-term retrieval (CLTR) and 30-minute delayed recall. Normative data used was that reported by Larrabee, et al.(38) for the six-trial version.

Rationale for Measure Selection

 Due to the inclusion of cognitive performance measures required in two of the three criteria sets under study (e.g., DSM-f and ICD-10 research), neuropsychological measures were not appropriate for inclusion as outcome measures. In lieu of this, outcome measures to contrast groups meeting vs. not meeting criteria were selected based on their relevance in assessing outcome following mTBI. Health-related quality of life has been demonstrated to be lower in those with mTBI(6,39-43) and in particular, patients with PCS/PCD(2,3,42). Psychiatric conditions are well-known and documented in mTBI, and depression is a frequently reported postinjury disorder. Although rates differ between studies, depression is a potent pre-injury factor(44-46) and post-mTBI symptom(44,47-50), and depression is often associated with elevated postconcussion symptom severity(51). Although specific postconcussion symptoms are required for diagnosis, the inclusion of a measure of general PCS-like symptoms appeared reasonable, especially as the symptom sets of the DSM-IV and ICD-10 are only partially overlapping with available measures such as the RPCSQ. Psychological resilience is a multi-factorial concept and has been difficult to define precisely; however, it is often conceptualized generally as the ability to maintain a sufficient psychological balance to maintain mental and physical functioning following exposure to aversive stress and/or trauma(52). Components of resilience have been elucidated suggesting that stressors present an opportunity for change/growth(53) and is integral to one’s adaptability to change, strong feelings of self-efficacy, and the formation of secure attachments to others(54) in addition to fostering sufficient tolerance of negative affect(55). In relation to persons with mTBI, McCauley et al.(46) found that preinjury level of resilience was significantly related to trauma-related anxiety and postconcussion symptom severity at one week and one month postinjury; these findings were recently replicated in a similar study by Sullivan et al.(56); resilience was also reported as a key predictor of experiencing PCS-like symptoms following mTBI even after accounting for host factors including age and gender(56). Given these findings, resilience appeared a reasonable attribute to assess as an outcome measure.

Acquisition of PCS/PCD Criteria: Data required to satisfy specific criteria for the diagnosis of PCS/PCD under ICD-10 and DSM-IV were collected in the following manner. Symptoms not included in the RPCSQ (e.g., reduced tolerance to stress, emotional excitement and alcohol, mood swings, etc.) were obtained using the same Likert-scale approach as that of the other RPCSQ symptom items. To consider a symptom as present, the rating for that symptoms had to indicate an increase from before their injury (e.g., a mild, moderate, or severe problem) and were present in the previous week. Structured follow-up questions were used to determine whether or not the symptoms were better accounted for by physical illness, over-the counter medications, illicit substances or alcohol use (DSM-IV criteria), and the level of preoccupation of the participant with her/his physical and/or mental symptoms (ICD-10) was rated as either not present or as mild, moderate, or severe using a standard set of behavioral anchor points. For the cognitive criterion (DSM-IV and ICD-10 research), Z-scores of < -1.5 for total recall and delayed recall of the BVMT-R (linearly transformed from computer-scored T-scores), CLTR and delayed recall of the VSRT, and either the oral or written score of the SDMT were considered indicators of deficits in attention or learning and memory. Only one score indicating impairment was required to satisfy the cognitive impairment criterion. A system of reliability codes ensured that test measures with no modifications or only minor deviations from normal administration were used in the statistical analyses. The investigators acknowledge that the DSM-IV criteria were designed to be used beginning at three months postinjury; however, in the interest of comparing the three criteria sets, this requirement was waived so that performance at each study occasion could be assessed. Procedure

A consecutive series of participants was prospectively screened and recruited from the emergency department (EDs) of the two American College of Surgeons Level-I trauma centers (Ben Taub General Hospital and Memorial Hermann Hospital-Texas Medical Center) in Houston, Texas by study personnel according to a rotating schedule representing all shifts and days of the week. The diagnosis of TBI was made by ED trauma physicians, and Glasgow Coma Scale (GCS) ratings were made by ED trauma physicians or staff. Abbreviated Injury Scale (AIS) ratings were made by AIS-trained research nurses based on thorough medical record review, and results of the AIS body-region severity codes were used to calculate the Injury Severity Score (ISS). All head CT scans were read and coded by a board-certified neuroradiologist.

Participants were administered a baseline assessment (21.8 + 11.5 hours after injury) of their neuropsychological and emotional status. In-person follow-up assessments were also conducted at one week, and at one, three, and six months postinjury by a bachelor’s-level research associate in the participant’s stated preferred language (English or Spanish). Research associates were not blinded to the participant’s injury group status (e.g., mTBI vs. orthopedic controls as part of the larger study). Informed consent was obtained from the participant through an informed consent form and procedure approved by the Institutional Review Boards of Baylor College of Medicine and the University of Texas Medical School-Houston and their affiliate institutions. No participants were recruited while in posttraumatic amnesia (PTA) which would have required consent by a legally authorized representative.

Data analysis

 All analyses were conducted using SAS software for Windows, Version 9.4(57). Independent variables were analyzed for outliers; no data points were excluded from the analysis due to extreme scores. Separate analyses were performed at each study occasion (e.g., one week, and one, three, and six months postinjury) using the General Linear Model (GLM) for analysis of variance (ANOVA) for unbalanced data. Bonferroni correction for multiple comparisons was used resulting in an [[α]] < .0008 (.05/60) when comparing groups meeting vs. not meeting criteria for PCS/PCD for the five main outcome measures at each of the four study occasions. Fisher’s Exact Test was used to determine the difference in rates of litigation and receipt of compensation payments between groups.

AUDIT = Alcohol Use Disorders Identification Test.

DAST-10 = Drug Abuse Screening Test, 10-item version.

BMI = Body Mass Index.

ISS = Injury Severity Score.

GCS = Glasgow Coma Scale score.

LOC = Loss of consciousness, medical chart documentation.

ATV = All-terrain vehicle.

VSVT = Victoria Symptom Validity Test, total items raw score.

* Fisher’s Exact Test.

Percentages presented in the table represent the percentages of those either meeting or not meeting PCS/PCD criteria who were involved in litigation or receiving compensation and not the total sample. Results indicate no difference in the rates of involvement in litigation or receiving compensation under any of the three diagnostic criteria sets. Percentages of those involved in litigation in the full sample of participants with mTBI were 17.3%, 10.9%, and 11.3% at 1, 3, and 6 months, respectively.

Percentages of those receiving insurance compensation in the full sample of participants with mTBI were 10.2%, 5.4%, and 5.6% at 1, 3, and 6 months, respectively.