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Systematic Review of Self-Reported Prognosis in Adults After Mild Traumatic Brain Injury: Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis

  • J. David Cassidy
    Correspondence
    Corresponding author J. David Cassidy, PhD, DrMedSc, University of Southern Denmark, Campusvej 55, Odense M, 5230 Denmark.
    Affiliations
    Institute of Sports Science and Clinical Biomechanics, Faculty of Health, University of Southern Denmark, Odense, Denmark

    Division of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada

    Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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  • Carol Cancelliere
    Affiliations
    Division of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada

    Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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  • Linda J. Carroll
    Affiliations
    School of Public Health and Alberta Centre for Injury Control and Research, School of Public Health, University of Alberta, Edmonton, Alberta, Canada
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  • Pierre Côté
    Affiliations
    Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Faculty of Health Sciences, University of Ontario Institute of Technology, Oshawa, Ontario, Canada

    UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, Toronto, Ontario, Canada
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  • Cesar A. Hincapié
    Affiliations
    Division of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada

    Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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  • Lena W. Holm
    Affiliations
    Division of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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  • Jan Hartvigsen
    Affiliations
    Institute of Sports Science and Clinical Biomechanics, Faculty of Health, University of Southern Denmark, Odense, Denmark

    Nordic Institute of Chiropractic and Clinical Biomechanics, Odense, Denmark
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  • James Donovan
    Affiliations
    Division of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Catharina Nygren-de Boussard
    Affiliations
    Department of Clinical Sciences, Rehabilitation Medicine, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
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  • Vicki L. Kristman
    Affiliations
    Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Department of Health Sciences, Lakehead University, Thunder Bay, Ontario, Canada

    Institute for Work and Health, Toronto, Ontario, Canada

    Division of Human Sciences, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada
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  • Jörgen Borg
    Affiliations
    Department of Clinical Sciences, Rehabilitation Medicine, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
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      Abstract

      Objective

      To update the mild traumatic brain injury (MTBI) prognosis review published by the World Health Organization Task Force in 2004.

      Data Sources

      MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from 2001 to 2012. We included published, peer-reviewed studies with more than 30 adult cases.

      Study Selection

      Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to assess subjective, self-reported outcomes. After 77,914 titles and abstracts were screened, 299 articles were eligible and reviewed for scientific quality. This includes 3 original International Collaboration on MTBI Prognosis (ICoMP) research studies.

      Data Extraction

      Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed each study and tabled data from accepted articles. A third reviewer was consulted for disagreements.

      Data Synthesis

      Evidence from accepted studies was synthesized qualitatively into key findings, and prognostic information was prioritized according to design as exploratory or confirmatory. Of 299 reviewed studies, 101 (34%) were accepted and form our evidence base of prognostic studies. Of these, 23 addressed self-reported outcomes in adults, including 2 of the 3 original ICoMP research studies. These studies show that common postconcussion symptoms are not specific to MTBI/concussion and occur after other injuries as well. Poor recovery after MTBI is associated with poorer premorbid mental and physical health status and with more injury-related stress. Most recover over 1 year, but persistent symptoms are more likely in those with more acute symptoms and more emotional stress.

      Conclusions

      Common subjective symptoms after MTBI are not necessarily caused by brain injury per se, but they can be persistent in some patients. Those with more initial complaints and psychological distress recover slower. We need more high-quality research on these issues.

      Keywords

      List of abbreviations:

      APOE (apolipoprotein E), ED (emergency department), GCS (Glasgow Coma Scale), ICoMP (International Collaboration on MTBI Prognosis), LOC (loss of consciousness), MTBI (mild traumatic brain injury), PCS (postconcussion syndrome), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), PTA (posttraumatic amnesia), PTHA (posttraumatic headache), PTSD (posttraumatic stress disorder), RPSQ (Rivermead Postconcussion Symptoms Questionnaire), SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey), WHO (World Health Organization)
      Mild traumatic brain injury (MTBI) is a common injury after falls and traffic collisions.
      • Styrke J.
      • Stålnacke B.M.
      • Sojka P.
      • Björnstig U.
      Traumatic brain injuries in a well-defined population: epidemiological aspects and severity.
      It represents 70% to 90% of all TBI and has been estimated to affect more than 600 adults per 100,000 each year.
      • Cassidy J.D.
      • Carroll L.J.
      • Peloso P.M.
      • et al.
      Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
      MTBI or concussion has received increasing attention mostly because of contact sports, especially American football and ice hockey.
      • McCrory P.
      • Meeuwisse W.
      • Johnston K.
      • et al.
      Consensus statement on concussion in sport—the 3rd International Conference on Concussion in Sport, held in Zurich, November 2008.
      As a result, there is more public attention and concern about potential long-lasting effects. Clinicians must deal with concerned patients who want to know how long their symptoms might last and what to expect in the future. These concerns can only be addressed by high-quality prognostic studies that follow up defined cohorts of injured subjects and use valid measures of prognostic factors and outcomes.
      In 2004, the World Health Organization (WHO) Collaborating Centre Task Force on MTBI published the first systematic review
      • Carroll L.J.
      • Cassidy J.D.
      • Peloso P.M.
      • et al.
      Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
      of the literature on the course and prognosis after MTBI. They searched MEDLINE, PsycINFO, CINAHL, and Embase up to the year 2000 and found 427 research articles on prognosis. After critically reviewing these studies, 120 (28%) were found to be of sufficient scientific quality to be included in their best-evidence synthesis. Of these studies, 16 focused on subjective symptoms in adults. The Task Force concluded that self-reported symptoms such as headache, fatigue, self-perceived cognitive deficits, and other symptoms reported after concussive events are also common in the acute stage of other injuries, and they are not specific to MTBI. Furthermore, these subjective symptoms are commonly associated with pain, depression, anxiety, posttraumatic stress, litigation, and other injury-related factors. Therefore, the Task Force recommended that postconcussion symptoms be assessed in the light of all contributing psychosocial factors and not be automatically attributed to brain injury per se. In addition, the use of terms such as postconcussion syndrome (PCS) might be misleading because of doubts about the etiology of some subjective postconcussion symptoms. The Task Force found that most patients recover within 3 months to a year but that compensation-related litigation can prolong recovery. Other factors associated with prolonged symptoms were preexisting physical limitations, prior brain injury, prior neurologic problems, psychiatric problems, stress, being a student, sustaining an MTBI in a motor vehicle collision, and age >40 years. They found evidence to suggest that premorbid personality and prior psychiatric history contribute to post-MTBI stress and psychological problems, which in turn are associated with more self-reported symptoms. Also, those with more severe MTBI (eg, Glasgow Coma Scale [GCS] score of 14 or 13 and MTBI complicated by intracranial lesions and/or depressed skull fracture) have more disability than those with a GCS score of 15. Overall the Task Force concluded that self-reported symptoms were common, but there was a need for more high-quality studies on their cause, course, and prognosis.
      The International Collaboration on MTBI Prognosis (ICoMP) is a team of clinicians and scientists assembled to update the WHO Collaborating Centre Task Force findings on MTBI.
      • Cancelliere C.
      • Cassidy J.D.
      • Côté P.
      • et al.
      Protocol for a systematic review of prognosis after mild traumatic brain injury: an update of the WHO Collaborating Centre Task Force findings.
      ICoMP includes many of the same members who served on that task force, and were selected for their expertise in epidemiology of MTBI, clinical management of MTBI, or both. Our purpose here is to update the WHO findings on course and prognosis in adults with respect to self-reported outcomes.

      Methods

      The literature search and critical review strategy are outlined in detail elsewhere. Briefly, the electronic databases MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were systematically searched from January 1, 2001, to June 30, 2011.
      • Cancelliere C.
      • Cassidy J.D.
      • Li A.
      • Donovan J.
      • Côté P.
      • Hincapié C.A.
      Systematic search and review procedures: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      These searches were updated on February 10, 2012. The reference lists of all reviews and meta-analyses related to MTBI, and articles meeting the eligibility criteria were screened for additional studies. ICoMP members also provided studies they had knowledge about. Articles were screened for eligibility according to predefined criteria. Included were original, published, peer-reviewed research reports in English, French, Swedish, Norwegian, Danish, and Spanish, and human participants of all ages. Studies had to have a minimum of 30 MTBI cases, and for this report, had to assess self-reported outcomes after adult MTBI. The definition of MTBI had to fall within the WHO Collaborating Centre Task Force
      • Carroll L.J.
      • Cassidy J.D.
      • Holm L.
      • Kraus J.
      • Coronado V.G.
      WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury
      Methodological issues and research recommendations for mild traumatic brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
      or the Centers for Disease Control and Prevention definitions.
      • Cancelliere C.
      • Cassidy J.D.
      • Côté P.
      • et al.
      Protocol for a systematic review of prognosis after mild traumatic brain injury: an update of the WHO Collaborating Centre Task Force findings.
      Excluded were publication types other than systematic reviews and meta-analyses that included an assessment of the methodological quality of the included studies, randomized controlled trials, cohort studies, and case-control studies. We also excluded basic science, animal, cadaveric, biomechanical, and laboratory studies. Although we screened systematic review reference lists for primary studies, we did not include systematic reviews in our critical review.
      All eligible articles were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network criteria.

      Scottish Intercollegiate Guidelines Network (SIGN). Available at: http://www.sign.ac.uk/. Accessed February 1, 2011.

      Two reviewers performed independent, in-depth methodological reviews of each eligible study, and a third reviewer was consulted for disagreements. Two reviewers independently extracted data from accepted articles into evidence tables, and this evidence was synthesized to provide clear and useful conclusions linked to the evidence tables. ICoMP members also undertook 3 original research projects, and 2 are included in the results of this article.
      We prioritized the evidence on prognostic factors using the framework described by Côté et al.
      • Côté P.
      • Cassidy J.D.
      • Carroll L.
      • Frank J.W.
      • Bombardier C.
      A systematic review of the prognosis of acute whiplash and a new conceptual framework to synthesize the literature.
      Phase I studies are hypothesis generating and explore associations between potential prognostic factors and disease outcomes in a descriptive, or crude univariate way. Phase II studies are exploratory analyses that focus on sets of prognostic factors or markers to discover which have the highest independent prognostic value. Phase III studies are confirmatory studies with explicit hypotheses and focused examination of the strength, direction, and independence of proposed causal relationships. Phase III studies are considered the strongest evidence for prognostic factors followed by phase II studies. Phase I studies are considered more preliminary.
      Our review was conducted and is reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      • PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      Our protocol was registered with the International Prospective Register of Systematic Reviews (registration no. CRD42011001410) and published in Systematic Reviews.
      • Cancelliere C.
      • Cassidy J.D.
      • Côté P.
      • et al.
      Protocol for a systematic review of prognosis after mild traumatic brain injury: an update of the WHO Collaborating Centre Task Force findings.

      Results

      After applying the inclusion and exclusion criteria to 77,914 titles and abstracts, 2170 full-text articles were assessed for eligibility. There were 173 eligible articles that assessed MTBI prognosis in adults, excluding studies of sport and military injuries, which are reported elsewhere.
      • Cancelliere C.
      • Hincapié C.A.
      • Keightley M.
      • et al.
      Systematic review of prognosis and return to play after sport concussion: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      • Boyle E.
      • Cancelliere C.
      • Hartvigsen J.
      • Carroll L.J.
      • Holm L.W.
      • Cassidy J.D.
      Systematic review of prognosis after mild traumatic brain injury in the military: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      Of the 173 articles on prognosis, 51 (29%) were evaluated as having a low risk of bias, and 21 of these included subjective, self-reported outcomes. The other studies reported on objective outcomes and are reported elsewhere.
      • Carroll L.J.
      • Cassidy J.D.
      • Cancelliere C.
      • et al.
      Systematic review of the prognosis after mild traumatic brain injury in adults: cognitive, psychiatric, and mortality outcomes: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      We also include 2 original studies addressing subjective outcomes in adult prognosis done by ICoMP members.
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      • Hartvigsen J.
      • Boyle E.
      • Cassidy J.D.
      • Carroll L.J.
      Mild traumatic brain injury after motor vehicle collisions: what are the symptoms and who treats them? A population-based 1-year inception cohort study.
      In total, 23 studies with self-reported outcomes, including 22 cohort studies and 1 nonrandomized experimental study, form the basis of this report (fig 1). Of the cohort studies, 1 is phase III, 16 are phase II, and 5 are phase I studies. All are English publications. We report our findings according to the length of follow up in these studies, including 1, 3, 6, 12, or more than 12 months of follow up.
      Figure thumbnail gr1
      Fig 1PRISMA flow diagram of literature inclusion/exclusion.

      Up to 1-month follow up

      We accepted 3 cohort studies from the United States that followed up patients for up to 1 month (table 1). Outcomes included self-reported irritability and executive functions, neurobehavioral function and symptoms, bodily pain, mental health, and postconcussion symptoms. One is a phase I study
      • Brewer T.L.
      • Metzger B.L.
      • Therrien B.
      Trajectories of cognitive recovery following a minor brain injury.
      and the other 2 are phase II studies.
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      • Rush B.K.
      • Malec J.F.
      • Moessner A.M.
      • Brown A.W.
      Preinjury personality traits and the prediction of early neurobehavioral symptoms following mild traumatic brain injury.
      All 3 studies recruited patients from hospitals, and 2 included an orthopedic injury group.
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      • Rush B.K.
      • Malec J.F.
      • Moessner A.M.
      • Brown A.W.
      Preinjury personality traits and the prediction of early neurobehavioral symptoms following mild traumatic brain injury.
      Table 1Prognostic studies of self-reported outcomes in adults with up to 1 month of follow up
      Author, Year, CountrySource Population, Study Size, Participation, F/UInclusion/Exclusion CriteriaMTBI Case DefinitionPrognostic Factors/Self-Reported OutcomesFindings
      Brewer et al,
      • Brewer T.L.
      • Metzger B.L.
      • Therrien B.
      Trajectories of cognitive recovery following a minor brain injury.
      2002; U.S.
      Convenience sample from university hospital ED (n=40)

      F/U: 24h, 48h, and 1mo
      Inclusion: age 18–59y, 21 male, 19 female, understand English, sufficient motor facility to manipulate Tinkertoys and paper and pencil. 25/40 (63%) had LOC.

      Exclusion: history of MTBI in last 6mo, substance abuse, domestic abuse, major psychiatric disorder, general anesthesia within 5y, or taking prescription drugs that alter cognition
      Physiological disruption of brain function followed by disturbance or LOC <10min; PTA <24h; mild alteration in mental status (eg, feeling dazed, disoriented, confused immediately after injury); GCS (if available) 13–15Prognostic factors: LOC present or absent

      Outcomes: irritability measured by items from 3 inventories: PHIQ (2 questions), MDI, and AFI (2 questions). Subjective measures of executive function were made using the AFI and PHIQ.
      30% self-reported irritability at 24h postinjury, and it was still 30% at 1mo. 60% self-reported concentration problems at 24h compared with 20% by 1mo.

      Phase I cohort: LOC did not impact self-reported irritability or concentration on the MDI. More LOC patients complained of more executive-type difficulties on the PHIQ at 1mo (28% LOC vs 18% no LOC).
      Landre et al,
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      2006; U.S.
      Consecutively admitted trauma patients at a level 1 trauma center recruited August 1998 through May 2000

      MTBI group: n=37; 34 had other injuries, 86% were injured in an MVC, and 63% had some LOC.

      Trauma group: n=39; 65% injured in an MVC

      Average F/U of 4–5d postinjury
      Inclusion: between the ages of 18 and 60y, fluent in English, and obtained a minimum score of 20 on the Mini-Mental State Examination

      Exclusion: positive findings on brain CT, histories of premorbid neurologic disorder (including moderate to severe TBI), psychiatric disorder, developmental disability; presence of MTBI case definition exclusion criteria
      American Congress of Rehabilitation Medicine, 1993: at least 1 of the following: (1) any period of LOC; (2) any loss of memory for events immediately before or after the accident; (3) any alteration in mental state at the time of the accident (eg, feeling dazed, disoriented, or confused); (4) focal neurologic deficit(s) that may or may not be transient.

      Exclusions: (1) LOC >30min; (2) GCS <13 after 30min; (3) PTA >24h
      Prognostic factors: injury status (MTBI vs control)

      Outcomes: bodily pain and mental health subscales of the SF-36 and a modified version of the PCSC
      Phase II cohort: There were no significant differences between groups on the SF-36 bodily pain or mental health subscale scores. Both groups scored low on the PCSC, and there was no difference between them with respect to frequency, intensity, or duration of symptoms.

      PCSC scores were correlated to the SF-36 mental health subscale, but not the bodily pain subscale. This suggests that PC symptoms are related to emotional distress but not to pain severity.
      Rush et al,
      • Rush B.K.
      • Malec J.F.
      • Moessner A.M.
      • Brown A.W.
      Preinjury personality traits and the prediction of early neurobehavioral symptoms following mild traumatic brain injury.
      2004; U.S.
      Consecutive hospital admissions for MTBI (n=87) or OI (n=82)

      F/U: to hospital discharge
      Inclusion: consented to participate, sustained either OI or MTBI requiring hospitalizationDiagnosis of TBI (as evidenced by abnormality on neurologic examination consistent with external trauma); GCS ≥13; absence of injury-related intracranial abnormality on CT scanPrognostic factors: preinjury personality traits (NEO-PI-R completed by injured and significant other)

      Outcomes: neurobehavioral function and symptoms measured by the NFI
      Phase II cohort: Self-ratings on the NFI did not differ between the OI and the MTBI groups. Self-ratings of personality did not predict NFI scores. Results suggest that early neurobehavioral symptoms after MTBI are related to the injury experience rather than the MTBI.
      Abbreviations: AFI, Attention Function Index; CT, computed tomography; F/U, follow-up; MDI, Multiscore Depression Inventory; MVC, motor vehicle collision; NEO-PI-R, NEO Personality Inventory–Revised; NFI, Neurobehavioral Functioning Inventory; OI, orthopedic injury; PC, postconcussion; PCSC, Postconcussion Symptom Checklist; PHIQ, Philadelphia Head Injury Questionnaire; U.S., United States.
      With respect to recovery, Brewer et al
      • Brewer T.L.
      • Metzger B.L.
      • Therrien B.
      Trajectories of cognitive recovery following a minor brain injury.
      found that 30% of patients continued to complain of irritability and 20% continued to complain of concentration problems at 1 month. Landre et al
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      found that patients with MTBI had similar Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) scores (bodily pain and mental health subscales) and frequency and intensity of postconcussion symptoms as patients with other traffic injuries. Rush et al
      • Rush B.K.
      • Malec J.F.
      • Moessner A.M.
      • Brown A.W.
      Preinjury personality traits and the prediction of early neurobehavioral symptoms following mild traumatic brain injury.
      reported a similar result comparing neurobehavioral function and symptoms at discharge between those with MTBI and those with orthopedic injuries. These results indicate that postconcussion symptoms, pain, and mental health are similar across acute injuries and not unique or specific to MTBI.
      With respect to prognosis, Brewer
      • Brewer T.L.
      • Metzger B.L.
      • Therrien B.
      Trajectories of cognitive recovery following a minor brain injury.
      suggests that the presence of loss of consciousness (LOC) does not impact self-reported irritability or concentration problems measured 1 month postinjury but might impact other executive functions. However, these findings are preliminary phase I findings. Landre
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      found that postconcussion symptoms reported within the first week after injuries are correlated to mental health but not bodily pain. This suggests these symptoms are related to emotional distress but not to pain severity. Rush
      • Rush B.K.
      • Malec J.F.
      • Moessner A.M.
      • Brown A.W.
      Preinjury personality traits and the prediction of early neurobehavioral symptoms following mild traumatic brain injury.
      reported that neurobehavioral function and symptoms were not associated with self-ratings of personality. However, both studies are phase II and exploratory with respect to prognosis.

      Up to 3 months' follow up

      The 3-month follow-up period is important because the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision stipulates that the criteria for a diagnosis of PCS include objective evidence of declines on neuropsychological testing, including difficulty in attention or memory, and 3 or more subjective symptoms present for at least 3 months (ie, fatigue; disordered sleep; headache; vertigo or dizziness; irritability or aggression with little or no provocation; anxiety, depression, or affective liability; changes in personality [eg, social or sexual inappropriateness]; or apathy or lack of spontaneity).
      • American Psychiatric Association
      Diagnostic and statistical manual of mental disorders (DSM-IV-TR).
      We accepted 5 studies
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      • Dischinger P.C.
      • Ryb G.E.
      • Kufera J.A.
      • Auman K.M.
      Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.
      that followed up patients for up to 3 months. Outcomes included various subjective symptoms (table 2). Two studies
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Dischinger P.C.
      • Ryb G.E.
      • Kufera J.A.
      • Auman K.M.
      Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.
      were from the United States, 2
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      were from Canada, and 1 study
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      was from Sweden. All are phase II cohort studies except for the study by Nygren-de Boussard et al,
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      which is a phase I cohort study.
      Table 2Prognostic studies of self-reported outcomes in adults with up to 3 months of follow up
      Author, Year, CountrySource Population, Study Size, Participation, F/UInclusion/Exclusion CriteriaMTBI Case DefinitionPrognostic Factors/Self-Reported OutcomesFindings
      Davis,
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      2002; U.S.
      Acutely injured patients (n=171) were recruited at University of California, Davis, Medical Center

      MTBI: n=102

      Other injuries: n=69

      Age-matched controls (uninjured): n=115 recruited from community.

      Baseline measures were made 1wk postinjury for all groups, and the MTBI group was followed up at 3mo.
      Inclusion: age 18–65y, English speaking, completion of preinjury and postinjury PCSQ, and biographic information 1wk after the injury

      Exclusion: past psychiatric hospitalization, hospitalization for substance abuse or dependency, or prior hospitalization for head injury
      American College of Rehabilitation Medicine criteria for MTBI—at least 1 of the following: (1) any period of LOC; (2) any loss of memory for events before/after accident; (3) any alteration in mental status at time of accident; (4) focal neurologic injuries that may or may not be transient. Severity of injury must not exceed (1) LOC for 30min; (2) initial GCS 13–15 at 30min after injury; and (3) PTA of 24h.Prognostic factors: injury status (MTBI vs other injuries)

      Outcomes: symptoms reported on the PCSQ

      Participants were asked to rate their preinjury symptoms and their postinjury symptoms at 1wk. MTBI group was also measured at 3mo.
      There were no significant differences between groups on postinjury PCSQ scores at 1wk.

      At 3mo, the MTBI group attributed more of their preinjury somatic symptoms to the injury and endorsed more memory symptoms.

      Phase II cohort: When compared with controls, both trauma groups endorsed significantly fewer symptoms in describing their preinjury status.
      Dischinger et al,
      • Dischinger P.C.
      • Ryb G.E.
      • Kufera J.A.
      • Auman K.M.
      Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.
      2009; U.S.
      180 MTBI patients admitted to a level 1 trauma center

      Baseline measures were made within 3–10d postinjury and F/U at 3mo postinjury.
      Inclusion: age 18–64y, acceptable score on Mini-Mental State Examination, and English speaking

      Exclusion: brain lesion requiring intervention; moderate/severe multiple injuries; focal neurologic findings; skull fracture requiring clinical intervention; cerebrospinal fluid leak requiring clinical intervention; prior moderate or severe brain injury; new or prior seizures; history of psychiatric disorder requiring hospitalization, or hallucinations; recent history of substance abuse; current probation/parole; and active duty in military
      American College of Rehabilitation Medicine definition: see previousPrognostic factors: PCS—6 physical (headache, dizziness, blurry/double vision, fatigue, sensitivity to light, sensitivity to noise), 3 cognitive (difficulty concentrating, memory problems, trouble thinking), and 3 emotional (anxiety, depression, irritability). Also sociodemographic factors: age, sex, education, history of substance abuse and depression

      Outcomes: PCS defined by 4 or more PC symptoms.
      At baseline, 84.2% had 4 or more PC symptoms, and 41.4% reported PCS at 3mo.

      Phase II cohort: PCS was associated with noise sensitivity (OR=3.06; 95% CI, 1.09–9.04) and female sex (OR=2.4; 95% CI, 1.10–5.32). Anxiety was associated with PCS in women only (OR=48.66; 95% CI, 7.50–315.8).
      Kashluba et al,
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      2004; Canada
      MTBI patients were drawn from consecutive admissions to 2 hospital emergency wards to participate in an RCT (n=118).

      Control group: n=118 uninjured adult participants recruited from university, hospital, and municipal government workplaces; matched on age, sex, years of education, and socioeconomic status to patients

      F/U: to 3mo
      Inclusion: 118 MTBI patients and controls enrolled in an RCT

      Exclusion: history of inpatient treatment for psychiatric disorder, mental retardation, inability to read English, history of TBI more severe than an MTBI, an MTBI within 1y before study, any central nervous system disorder, and concurrent pregnancy
      American Congress of Rehabilitation Medicine (1993)
      Mild Traumatic Brain Injury Committee, Head Injury Interdisciplinary Special Interest Group, American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J Head Trauma Rehabil 1993;8:86-7.
      Prognostic factors: PCL, which measures incidence and severity of symptoms of PCS

      Outcome: PCL at 3mo
      Overall, the MTBI patients improved substantially by 3mo and did not differ much from healthy controls.

      Phase II cohort: At F/U, MTBI patients did not endorse significantly more PCL symptoms than controls (group means: 14.09±10.77 vs 12.56±8.46). MTBI patients had a higher incidence of doing things more slowly, fatiguing quickly, and having poorer balance than controls. More MTBI patients endorsed at least 1 symptom in the severe range compared with controls (39% vs 15%). Poor balance and slowness best differentiated MTBI from controls.
      Lange et al,
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      2010; Canada
      MTBI patients (n=86) referred to a hospital-based, early intervention concussion clinic

      Controls (n=177) recruited from university and local community

      Patients were evaluated on average 1.8mo after their injury.
      Inclusion: patients evaluated within 8mo of injury (most evaluated within 3mo of injury) and fluent in English

      Controls excluded if they had mental health problems, substance abuse, or neurologic problems
      WHO Collaborating Centre Task Force on MTBI, including: (1) 1 or more of the following: confusion or disorientation, LOC ≤30min, PTA <24h, and/or other transient neurologic abnormalities such as focal signs, seizure, and IC lesion not requiring surgery; and (2) GCS 13–15 after 30min postinjury or later on presentation for health carePrognostic factor: litigation

      Outcomes: preinjury and postinjury frequency and intensity of 13 PC symptoms measured by BC-PSI
      MTBI patients’ preinjury BC-PSI total scores were significantly lower than control subjects’ total scores (small effect size, .27).

      Preinjury symptoms most frequently present:

      Control group: fatigue (39%), headache (26.6.%), and poor sleep (32.8%)

      MTBI group: fatigue (25.6%), irritability (25.6%), headache (20.9%), and poor sleep (30.2%)

      Postinjury, the MTBI group complained of more symptoms: fatigue (76.7%), irritability (74.4%), headache (80.2%), and poor sleep (73.3%).

      Phase II cohort: Patients in litigation (n=34) reported more postinjury symptoms (medium-large effect size, .63), even though they did not have a more serious injury at baseline (ie, LOC, PTA, or abnormal CT scan findings).
      Nygren-de Boussard et al,
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      2005; Sweden
      MTBI patients (n=122) consecutively recruited from 3 hospital EDs from January 2000 through December 2001

      Noninjured controls (n=35) of similar age, sex, and socioeconomic status used to standardize S100 serum protein levels

      F/U: 3mo
      Included patients with blunt trauma to the head seen within 24h of injury, and age 15–65y. Included controls aged 15–65y, in good health, and no history of recent head trauma

      Excluded patients with no clear history of blunt trauma, or other major injuries, or major neurologic disorders. Those with prior or current psychiatric illness or alcohol dependence were not excluded.
      MTBI: blunt head trauma with GCS 14–15, LOC no more than 30min, PTA no more than 24hPrognostic factors: S100B and S100A1B (reference values determined as ≤97.5 percentile of uninjured controls)

      Outcome: PC symptoms assessed by RPSQ
      31% of patients had S100B concentrations above the cutoff, and 48% had S100A1B concentrations above cutoff.

      44% reported at least 1 cognitive symptom on the RPSQ at day 1, 45% on day 7, 27% on day 14, and 26% at 3mo.

      Phase I cohort: no association between S100 and cognitive symptoms. Self-reported cognitive symptoms were not associated with objective cognitive testing results.
      Abbreviations: BC-PSI, British Columbia Postconcussion Symptom Inventory; CI, confidence interval; CT, computed tomography; F/U, follow up; IC, intracranial; OR, odds ratio; PC, postconcussion; PCL, Problem Checklist; PCSQ, Postconcussion Symptom Questionnaire; RCT, randomized controlled trial; RPSQ, Rivermead Postconcussion Symptoms Questionnaire; U.S., United States.
      Mild Traumatic Brain Injury Committee, Head Injury Interdisciplinary Special Interest Group, American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J Head Trauma Rehabil 1993;8:86-7.
      Four of these studies
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      compared patients with MTBI to uninjured controls, and Davis
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      also included a second control group of patients with other injuries. Four studies
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      • Dischinger P.C.
      • Ryb G.E.
      • Kufera J.A.
      • Auman K.M.
      Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.
      recruited acute patients seen at hospitals, but Lange et al
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      recruited patients referred to an early intervention clinic. Two of these studies
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      found little difference in postconcussion symptoms reported after injury when comparing patients with MTBI and controls, although Davis
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      found that patients with MTBI tended to underreport existing symptoms before their injury when compared with healthy controls. They also found that patients with MTBI attribute more of their preinjury somatic symptoms to the injury and endorse more memory symptoms. Kashluba et al
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      found that patients with MTBI improved substantially and did not endorse significantly more postconcussion symptoms than controls at 3 months postinjury. However, they did have a higher incidence of doing things more slowly, fatiguing quickly, and having poor balance compared with controls. Also, more patients with MTBI endorsed at least 1 symptom in the severe range compared with controls (39% vs 15%). However, Lange
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      showed that even though patients with MTBI endorse more symptoms than healthy controls, they recall fewer symptoms than controls before injury. They concluded that patients with MTBI misperceive their preinjury status as better than the average, and they called this the “good-old-days” bias because of the potential of misattributing symptoms to the injury. The weight of this evidence suggests that postconcussion symptoms are not specific to MTBI, and clinicians should be cautious about attributing common postinjury symptoms to the MTBI. This calls into question the validity of diagnosing PCS.
      Nevertheless, postconcussion symptoms are troublesome for patients. Dischinger et al
      • Dischinger P.C.
      • Ryb G.E.
      • Kufera J.A.
      • Auman K.M.
      Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.
      followed up 180 patients with MTBI to see how many developed PCS 3 months after the injury. They defined PCS as having 4 or more symptoms that could include any of 6 physical symptoms (headache, dizziness, blurry/double vision, fatigue, sensitivity to light, sensitivity to noise), 3 cognitive symptoms (difficulty concentrating, memory problems, trouble thinking), or 3 emotional symptoms (anxiety, depression, irritability). At baseline, 84.2% had 4 or more postconcussion symptoms. At 3 months, 41.4% had PCS, and it was associated with female sex, baseline noise sensitivity, and baseline anxiety in women only. Furthermore, Lange et al
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      found that patients in litigation report more postconcussion symptoms than MTBI nonlitigants. All this highlights the complexity of symptom attribution after MTBI and the interactions of biopsychosocial issues.
      Finally, Nygren-de Boussard et al
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      reported a phase I study of the relationship between the serum concentrations of proteins S100A1B and S100B and prognosis. S100 proteins are biochemical markers of acute brain injury, and if present and associated with cognitive impairment, might be used as a prognostic marker. Baseline S100A1B and S100B serum concentrations were elevated in 48% and 31% of the patients, respectively, and 44% reported at least 1 cognitive symptom at baseline and 26% at 3 months. However, there was no association between elevated S100 levels and cognitive symptoms at any time point. This suggests that these markers are not useful in MTBI prognosis with respect to subjective outcomes.

      Up to 6 months' follow up

      Six studies were accepted that reported follow up of patients for up to 6 months, including 2 from the United Kingdom,
      • De Silva M.J.
      for the CRASH Trial Collaborators
      Patient outcome after traumatic brain injury in high-, middle- and low-income countries: analysis of data on 8927 patients in 46 countries.
      • Hou R.
      • Moss-Morris R.
      • Peveler R.
      • Mogg K.
      • Bradley B.P.
      • Belli A.
      When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.
      and 1 each from Israel,
      • Gil S.
      • Caspi Y.
      • Ben-Ari I.Z.
      • Koren D.
      • Klein E.
      Does memory of a traumatic event increase the risk for posttraumatic stress disorder in patients with traumatic brain injury? A prospective study.
      New Zealand,
      • Norrie J.
      • Heitger M.
      • Leathem J.
      • Anderson T.
      • Jones R.
      • Flett R.
      Mild traumatic brain injury and fatigue: a prospective longitudinal study.
      The Netherlands,
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      and Canada.
      • Tellier A.
      • Marshall S.C.
      • Wilson K.G.
      • Smith A.
      • Perugini M.
      • Stiell I.G.
      The heterogeneity of mild traumatic brain injury: where do we stand?.
      Five are phase II studies and 1 is a phase I study. Outcomes included functional disability measured by the Glasgow Outcome Scale, posttraumatic symptoms, posttraumatic stress disorder (PTSD), PCS (ie, defined by ≥3 symptoms on the Rivermead Postconcussion Symptoms Questionnaire [RPSQ]), self-reported symptoms, and community integration (table 3). None of these studies included control groups, and they all included acute patients recruited from hospitals.
      Table 3Studies of self-reported outcomes in adults with up to 6 months of follow up
      Author, Year, CountrySource Population, Study Size, Participation, F/UInclusion/Exclusion CriteriaMTBI Case DefinitionPrognostic Factors/Self-Reported OutcomesFindings
      de Silva et al,
      • De Silva M.J.
      for the CRASH Trial Collaborators
      Patient outcome after traumatic brain injury in high-, middle- and low-income countries: analysis of data on 8927 patients in 46 countries.
      2009; UK/global
      8927 TBI patients from 46 high-, middle-, and low-income countries from the multicentered CRASH trial; n=2676 with MTBI

      F/U: to 6mo postinjury
      Inclusion: ≥16y of age and GCS ≤14.

      Exclusion: patients who had a disability that was not caused by their TBI
      GCS 13–14Prognostic factors: countries were classified using the World Bank Atlas as either high-income (GNP
      Millions of U.S. dollars.
      ≥$10,066) or middle-/low-income country (GNP
      Millions of U.S. dollars.
      ≤$10,065).

      Outcomes:

      GOS: disability defined as anything less than good recovery
      60% of MTBI patients in high-income countries had good recovery compared with 78% in middle-/low-income countries.

      Phase II cohort: The risk of moderate disability (OR=.41; 95% CI, .30–.56) and severe disability (OR=.41; 95% CI, .23–.72) was less for MTBI patients in middle-/low-income vs high-income countries.
      Gil et al,
      • Gil S.
      • Caspi Y.
      • Ben-Ari I.Z.
      • Koren D.
      • Klein E.
      Does memory of a traumatic event increase the risk for posttraumatic stress disorder in patients with traumatic brain injury? A prospective study.
      2005; Israel
      120 MTBI patients recruited from 2 surgical wards of a hospital

      F/U: 1wk, 1mo, and 6mo
      Inclusion criteria: age 18–50y and fluent in Hebrew

      Exclusion criteria: actively receiving psychiatric care, prior history of head trauma, cognitive deficit, substance abuse, and major untreated medical condition
      MTBI defined as GCS 13–15 at the time of admission. None had LOC at the time of admission.Prognostic factors: memory of the injury event within the first 24h of injury. Also, measures of depression and anxiety at 1wk using BDI and BAI, acute posttraumatic symptoms using PTSS and the CA-PTSDS, history of psychiatric disorder, age, sex, education, Injury Severity Score, marital status, country of origin, history of physical illness

      Outcome: PTSD diagnosis based on CA-PTSDS and PTSS
      By 6mo, 14% had developed PTSD. PTSD was more prevalent in those with a memory of the injury event (23%) than those without memory (6%). This difference was primarily due to “reexperiencing” cluster of symptoms.

      Phase II cohort: PTSD was associated with memory of event (OR= 2.2; 95% CI, 1.0–10.1), acute posttraumatic symptoms (OR=5.3; 95% CI, 1.1–9.3 for CA-PTSDS; and OR=5.2; 95% CI, 1.0–9.4 for PTSS), anxiety (OR=4.9; 95% CI, 1.0–9.1), depression (OR=5.1; 95% CI, 1.0–9.2), and history of psychiatric disorder (OR=3.7; 95% CI, 1.1–8.9)
      Hou et al,
      • Hou R.
      • Moss-Morris R.
      • Peveler R.
      • Mogg K.
      • Bradley B.P.
      • Belli A.
      When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.
      2012; UK
      MTBI patients (N=126) seen at an ED of a general hospital

      F/U: 3 and 6mo
      Inclusion: age 18–60y

      Exclusion: those with multitrauma requiring hospitalization and those with major neurologic or psychiatric disorders
      Traumatically induced physiological disruption of brain function with at least 1 of the following: LOC ≤15min, PTA ≤60min, any alteration in mental state at the time of the injury, lack of focal neurologic deficit, and GCS 13–15Prognostic factors: BIPQ measures patients' perceptions of their injury, BRIQ measures behavior after onset of illness/injury and the “all or nothing” subscale measures patterns of activity and rest, HADS, IES measures distress after the injury, Brief SSQ measures perceived social support including availability and satisfaction, sex, age, GCS 14 or 15, LOC, PTA, education, marital status, occupation, and litigation status

      Outcome: PCS defined by ICD-10 criteria of ≥3 of headache, dizziness, fatigue, irritability, insomnia, concentration problems, memory difficulty, or intolerance of stress, emotion or alcohol measure using RPSQ
      PCS was present in 22% at 3mo and 21% at 6mo. Fatigue, forgetfulness, and sleep disturbance were most commonly reported at 3mo. Headache, fatigue, and sleep disturbance were most commonly reported at 6mo. No significant recovery from PCS occurred from 3 to 6mo.

      Phase II cohort: At 3mo, the baseline “all or nothing” subscale score of the BRIQ was the only variable associated with PCS (OR=1.14; 95% CI, 1.05–1.24; P=.002). At 6mo, negative head injury perceptions from the BIPQ were associated with PCS (OR=1.05; 95% CI, 1.01–1.10; P=.02). Cognitive and behavioral responses to head injury might be more important in the development of PCS than emotional and social factors.
      Norrie et al,
      • Norrie J.
      • Heitger M.
      • Leathem J.
      • Anderson T.
      • Jones R.
      • Flett R.
      Mild traumatic brain injury and fatigue: a prospective longitudinal study.
      2010; New Zealand
      MTBI patients (N=159) seen in the ED of a hospital over a 2-y period.

      F/U: 3 and 6mo
      Inclusion: patients with full F/U data and did not report confounding temporary illnesses over the F/U period

      Exclusion: abnormal CT scan findings, intake of psychoactive drugs or history of drug abuse, central neurologic or psychiatric condition, skull/facial fracture, and trauma to other parts of body
      GCS 13–15, LOC <20min, and PTA <24hPrognostic factors: early fatigue severity assessed at 1wk by the FSS, depression and anxiety measured by the HADS

      Outcome: fatigue prevalence defined as a F/U score of ≥2 on the RPSQ–item 6 about fatigue
      Fatigue prevalence diminished from 67.3% at 1wk to 29.6% at 3mo. It remained relatively stable at 26.4% at 6mo.

      Phase II cohort: Fatigue severity and depression at 3mo were associated with fatigue prevalence at 6mo. Anxiety at 3mo was not associated with fatigue at 6mo.
      Stulemeijer et al,
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      2008; The Netherlands
      MTBI patients (N=201) admitted to a level 1 trauma center

      F/U: 6mo postinjury
      Inclusion: age 18–60y, able to speak and write in Dutch, no premorbid mental retardation or dementia

      Exclusion: questionnaires that were completed >6wk postinjury
      European Federation of Neurological Societies’ definition of MTBI: history of impact to head with or without LOC ≤30min, with or without PTA, and admission GCS of 13–15Prognostic factors:
      • 1.
        Preinjury: age, sex, education, emotional problems, physical comorbidities, or prior head injury
      • 2.
        Peri-injury: GCS, LOC, PTA duration, brain CT abnormality, early symptoms (ie, dizziness, nausea/vomiting, headache), additional extracranial injuries (ie, score ≥2 on the AISS)
      • 3.
        Early postinjury: PC symptoms (RPSQ), posttraumatic stress (IES with scores >26 classified as severe), severe fatigue (AFQ with a cutoff value of 20), pain severity score in 5 body regions), self-efficacy (ie, GSES median split)
      Outcome:

      RPSQ: recovered defined as a score <3 on at least 13 of 16 PC symptoms
      64% reported full recovery (ie, absence of PC symptoms).

      Phase II prediction rule: Absence of comorbid physical problems (OR=3.5; 95% CI, 1.6–7.8), low levels of early PC symptoms (OR=5.5; 95% CI, 2.3–13.2), and low levels of early posttraumatic stress (OR=10.0; 95% CI, 2.3–42.9) predicted low PC symptoms (ie, 90% chance of remaining free of PCS). Discriminative ability was good with AUC=.73.

      The rule identified patients with a 90% probability of low PC symptoms at 6-mo F/U.
      Tellier et al,
      • Tellier A.
      • Marshall S.C.
      • Wilson K.G.
      • Smith A.
      • Perugini M.
      • Stiell I.G.
      The heterogeneity of mild traumatic brain injury: where do we stand?.
      2009; Canada
      MTBI patients (N=125) presenting to the ED of a trauma center

      F/U: 6mo
      Inclusion: patients presenting to ED and agreed to participateMTBI defined as lowest GCS 13–15, LOC <30min, and PTA up to 24hPrognostic factors: GCS 15 vs GCS 13–14; PTA length (≤30min, >30min), prior TBI

      Outcomes: self-reported symptoms assessed with the NFI, CIQ Productivity Scale, and a postconcussive checklist developed by the authors, including measures of fatigue, disordered sleep, headaches, vertigo or dizziness, irritability, and changes in mood or personality
      Phase I cohort: GCS score was not associated with symptom differences at 6mo. At 6mo, those with longer PTA showed greater aggressive and disinhibited behaviors on the NFI. Prior TBI not associated with self-reported outcomes
      Abbreviations: AFQ, Abbreviated Fatigue Questionnaire; AISS, Abbreviated Injury Severity Score; AUC, area under the curve; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; BIPQ, Brief Illness Perception Questionnaire; BRIQ, Behavioral Response to Illness Questionnaire; CA-PTSDS, Clinician-Administered Posttraumatic Stress Disorder Scale; CI, confidence interval; CIQ, Community Integration Questionnaire; CRASH, Corticosteroid Randomization After Significant Head injury; CT, computed tomography; FSS, Fatigue Severity Scale; F/U, follow up; GNP, gross national product; GOS, Glasgow Outcome Scale; GSES, General Self-Efficacy Scale; HADS, Hospital Anxiety and Depression Scale; ICD-10, International Statistical Classification of Diseases, 10th Revision; IES, Impact of Event Scale; NFI, Neurobehavioral Functioning Inventory; OR, odds ratio; PC, postconcussion; PTSS, Posttraumatic Stress Scale; RTW, return to work; SSQ, Social Support Questionnaire; UK, United Kingdom.
      Millions of U.S. dollars.
      With respect to course and prognosis, Gil et al
      • Gil S.
      • Caspi Y.
      • Ben-Ari I.Z.
      • Koren D.
      • Klein E.
      Does memory of a traumatic event increase the risk for posttraumatic stress disorder in patients with traumatic brain injury? A prospective study.
      showed that by 6 months, 14% of patients with MTBI had developed PTSD. It was more prevalent in those with a memory of the injury event (23%) than those without memory (6%). This difference was primarily due to the “reexperiencing” cluster of symptoms. PTSD was also associated with acute posttraumatic symptoms, anxiety, depression, and a history of psychiatric disorder. Hou et al
      • Hou R.
      • Moss-Morris R.
      • Peveler R.
      • Mogg K.
      • Bradley B.P.
      • Belli A.
      When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.
      found that PCS was present in 22% of patients at 3 months and 21% at 6 months. Fatigue, forgetfulness, and sleep disturbance were most commonly reported at 3 months, and PCS was associated with self-reported activity levels. Headache, fatigue, and sleep disturbance were most commonly reported at 6 months, and PCS at 6 months was associated with negative head injury perceptions. These results suggest that cognitive and behavioral responses to MTBI might be more important in the development of PCS than demographics, injury severity, and other emotional and social factors. Norrie et al
      • Norrie J.
      • Heitger M.
      • Leathem J.
      • Anderson T.
      • Jones R.
      • Flett R.
      Mild traumatic brain injury and fatigue: a prospective longitudinal study.
      found that fatigue prevalence diminished from 67.3% at 1 week to 29.6% at 3 months and 26.4% at 6 months. Further, fatigue severity and depression measured at 3 months were associated with fatigue prevalence at 6 months. All of these studies indicate that postconcussion symptoms continue to persist in 14% to 26% of patients with MTBI at 6 months. However, all of these studies are phase II and require confirmation.
      Three other studies followed up patients for up to 6 months. De Silva et al
      • De Silva M.J.
      for the CRASH Trial Collaborators
      Patient outcome after traumatic brain injury in high-, middle- and low-income countries: analysis of data on 8927 patients in 46 countries.
      compared functional outcomes after more severe MTBI (GCS score, 13–14) across low-, middle-, and high-income countries using the Glasgow Outcome Scale. In this phase II study they found that 6-month recovery was better in patients from low-income countries compared with high-income countries (78% vs 60%). They speculate that sociocultural or environmental factors are responsible. Tellier et al
      • Tellier A.
      • Marshall S.C.
      • Wilson K.G.
      • Smith A.
      • Perugini M.
      • Stiell I.G.
      The heterogeneity of mild traumatic brain injury: where do we stand?.
      compared 6-month outcomes in patients with MTBI with GCS scores of 13 or 14 with those with a GCS score of 15 and found no difference in postconcussion symptom prevalence. However, they did find that those with longer posttraumatic amnesia (PTA) showed greater aggressive and disinhibited behaviors. This is a phase I study, and the results should be viewed as exploratory.
      Finally, the study by Stulemeijer et al
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      deserves special attention. They developed and internally validated a clinical prediction rule for good recovery, defined as a score of 0 (no problem), 1 (not a problem anymore), or 2 (mild problem but not interfering with daily activities) on 13 of 16 postconcussion symptoms measured by the RPSQ. If the patient did not have any preinjury comorbid physical problems, had low levels of early postconcussion symptoms (ie, a score of 0 [no problem], 1 [not a problem anymore], or 2 [mild, but not interfering with daily activities] on at least 13 of the 16 postconcussion symptoms measured by the RPSQ), and had low levels of early posttraumatic stress, they had a 90% chance of a good recovery. LOC, GCS, PTA, and abnormal computed tomography findings did not predict recovery. These results show that early identification of patients with MTBI who are likely to have good recovery is feasible, but Stulemeijer's prediction rule needs to be validated in another setting before it can be recommended for widespread use.

      Up to 1-year follow up

      Six accepted cohort studies reported 1-year follow up of patients, including 3 studies from Canada,
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      • Hartvigsen J.
      • Boyle E.
      • Cassidy J.D.
      • Carroll L.J.
      Mild traumatic brain injury after motor vehicle collisions: what are the symptoms and who treats them? A population-based 1-year inception cohort study.
      • Friedland J.F.
      • Dawson D.R.
      Function after motor vehicle accidents: a prospective study of mild head injury and posttraumatic stress.
      2 from the United States,
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      • McLean S.A.
      • Kirsch N.L.
      • Tan-Schriner C.U.
      • et al.
      Health status, not head injury, predicts concussion symptoms after minor injury.
      and 1 study from Lithuania
      • Stovner L.J.
      • Schrader H.
      • Mickeviciene D.
      • Surkiene D.
      • Sand T.
      Headache after concussion.
      (table 4). One is a phase III study,
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      3 are phase II studies,
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      • McLean S.A.
      • Kirsch N.L.
      • Tan-Schriner C.U.
      • et al.
      Health status, not head injury, predicts concussion symptoms after minor injury.
      • Stovner L.J.
      • Schrader H.
      • Mickeviciene D.
      • Surkiene D.
      • Sand T.
      Headache after concussion.
      and 2 are phase I studies.
      • Hartvigsen J.
      • Boyle E.
      • Cassidy J.D.
      • Carroll L.J.
      Mild traumatic brain injury after motor vehicle collisions: what are the symptoms and who treats them? A population-based 1-year inception cohort study.
      • Friedland J.F.
      • Dawson D.R.
      Function after motor vehicle accidents: a prospective study of mild head injury and posttraumatic stress.
      Outcomes include self-reported recovery, levels of fatigue, perceived activities and behaviors, satisfaction with reintegration to normal living, posttraumatic stress, psychiatric impairment, postconcussion symptoms, depressive symptomatology, health care use, PCS as defined by >3 symptoms on the RPSQ, and the prevalence of posttraumatic headache (PTHA).
      Table 4Studies of self-reported outcomes in adults with up to 1 year of follow up
      Author, Year, CountrySource Population, Study Size, Participation, F/UInclusion/Exclusion CriteriaMTBI Case DefinitionPrognostic Factors/Self-Reported OutcomesFindings
      Cassidy et al,
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      2013; Canada
      MTBI patients (N=1716) treated after a traffic injury

      F/U: 6wk, 3, 6, 9, and 12mo
      Inclusion: all Saskatchewan residents aged ≥18y or older who were treated for, or made an insurance claim for, a traffic injury over a 2-y period

      Exclusion: those who made a claim, or were treated for a traffic injury more than 42d after the collision, or sustained a serious injury (ie, died, could not answer questionnaire because of injury), or could not understand English. Also excluded were workers’ compensation claims and those with LOC >30min.
      Answered yes to “Did you hit your head in the collision” and answered “yes” or “don’t know” to 1 of the following: LOC, PTA, disorientation or confusion. Also had to answer, “yes” to having at least 1 of the following symptoms: dizziness or unsteadiness, memory problems or forgetfulness, and concentration or attention problems.Prognostic factors: demographics (age, sex, income, marital status, education), position in vehicle, days in hospital, symptoms (checklist of PC symptoms), fractured bones, LOC, PTA, pain intensity (NRS-11: neck, headache, face, low back, midback, arms, hands, leg, foot, and abdomen, chest, or groin), prior health, current health, expectations for recovery, depression (CES-D cut point 16), and number of comorbid health conditions.

      Outcomes: self-reported recovery (ie, “all better or cured” or “very much improved”)
      Course: Median time to recovery was 100d (95% CI, 97–103).

      Phase II cohort: Factors associated with recovery were age >50y vs 18–23y (HRR=.76; 95% CI, .63–.91); > high school education vs some high school (HRR=1.24; 95% CI, 1.07–1.44); expectations for recovery—(1) never get better (HRR=.26; 95% CI, .14–.50), (2) don’t know when will get better (HRR=.52; 95% CI, .43–.63), and (3) will get better slowly (HRR=.79; 95% CI, .67–.94) compared with (4) get better soon; depression (HRR=.99; 95% CI, .99–1); arm numbness (HRR=.83; 95% CI, .73–.94); hearing problems (HRR=.75; 95% CI, .59–.96); confusion after collision—don’t know (HRR=.78; 95% CI, .62–.96) vs none; low back pain intensity (HRR=.97; 95% CI, .95–.98); headache intensity (HRR=.98; 95% CI, .96–1); and mid-back pain intensity (HRR=.97; 95% CI, .95–.99).
      de Leon et al,
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      2009; U.S.
      Patients (N=359) from level 2 trauma center at community hospital ED.

      N1=58: MTBI with LOC ≤30min, and/or PTA <24h.

      N2=173 MTBI with no PTA/LOC.

      N3=128 other mild non-head injuries (25% sprains, 24% contusions, 16% lacerations, 21% closed fractures, 14% others).

      F/U: 12mo
      Inclusion: age ≥18y, presented within 24h of injury, GCS ≥13, did not require adult trauma team, discharged directly from ED, Mini-Mental State Examination of at least 18, and able to describe elements of the study to a research assistant.

      Exclusion: transfer from another hospital, non-English speaking, being incarcerated, hospital admission, evidence of still being in a state of PTA, LOC ≥30min, or LOC not attributable to trauma
      CDC criteria: GCS ≥13 on ED arrival and ≥1 of the following: (1) LOC ≤30min, (2) PTA, or (3) ≥2 PC symptoms (symptoms rated at least “mild” on RPSQ). Patients without direct head impact injury but with LOC/PTA caused by trauma were classified as having MTBI if there was no other demonstrable cause for LOC.Prognostic factors: injury group, preinjury health status variables including baseline fatigue; medical variables including having a past medical disability or a history of psychological or mental health problems, ISS, injury characteristics and cause; demographic variables including age, sex, education, marital status, employment status, and ethnicity; and litigation status

      Outcome: fatigue measured by SF-36 vitality subscale.
      SF-36 vitality scores for all injured patients were within population norms by 12-mo F/U. The less severe MTBI group (N2) with no PTA/LOC had more fatigue (lower mean score ± SD) at 12mo than the other groups: N1=52.3±12.22; N2=49.6±11.83; N3=53.0±10.37.

      Phase III cohort: Worse fatigue at 12mo was associated with preinjury fatigue, marital status (ie, separated, divorced, or widowed), lawyer involvement, and baseline poor medical and mental health. Having a head injury did not result in more fatigue than having a non-head injury. Psychosocial factors were associated with more fatigue.
      Friedland et al,
      • Friedland J.F.
      • Dawson D.R.
      Function after motor vehicle accidents: a prospective study of mild head injury and posttraumatic stress.
      2001; Canada
      MTBI patients (n=64) admitted to tertiary hospital after MVC

      Non–head-injured controls (n=35) admitted to the same hospital after MVC

      F/U: 6 to 9mo
      Inclusion criteria: admission to hospital after an MVC, age 19–65y, and English speaking

      Exclusion: prior history of head injury, neurologic disease or hospitalization for psychiatric illness, severe disfigurement, amputation, or spinal cord injury.

      Non-TBI group excluded if they had LOC, PTA, GCS <15, abnormal CT scan findings if taken, or documented brain injury in medical chart
      American Congress of Rehabilitation Medicine criteria: GCS of 13–15 after 30min, LOC ≤30min, or PTA ≤24hPrognostic factors: type of injury (MTBI vs other)

      Outcomes: SIP and RNL, IES to measure posttraumatic stress, and GHQ-12 to measure psychiatric impairment
      Phase I cohort: MTBI group had lower psychosocial scores on SIP (21.1 vs 10.9) than the non-head injury group. There was no difference on the RNL or GHQ-12 across injury groups. MTBI and non-MTBI group had similar levels of posttraumatic stress.

      Those with no symptoms of posttraumatic stress were less likely to have lost consciousness.
      Hartvigsen et al,
      • Hartvigsen J.
      • Boyle E.
      • Cassidy J.D.
      • Carroll L.J.
      Mild traumatic brain injury after motor vehicle collisions: what are the symptoms and who treats them? A population-based 1-year inception cohort study.
      2013; Canada
      MTBI patients (N=1716) treated after a traffic injury

      F/U: 6wk, 3, 6, 9 and 12mo
      Inclusion: all Saskatchewan residents aged ≥18y who were treated for, or made an insurance claim for, a traffic injury over a 2-y period.

      Exclusion: those who made a claim, or were treated for a traffic injury more than 42d after the collision, or sustained a serious injury (ie, died, could not answer questionnaire because of injury), or could not understand English. Also excluded were workers’ compensation claims and those with LOC >30min.
      Answered yes to “Did you hit your head in the collision” and answered “yes” or “don’t know” to 1 of the following: LOC, PTA, disorientation or confusion. Also had to answer “yes” to having at least 1 of the following symptoms: dizziness or unsteadiness, memory problems or forgetfulness, and concentration or attention problemsPrognostic factors: none

      Outcomes: symptoms (checklist of PC symptoms, depression using CES-D cut point 16, pain at various body regions) and type of health practitioner care at follow-up interviews (MD, PT, DC, and RMT)
      Most common symptoms:

      At 6wk: sleep disturbance (65%), tiredness (59%), neck pain (50%), headache (39%), dizziness (39%), and low back pain (35%). 75% of those with symptoms reported more than 3 symptoms.

      At 1y: sleep disturbances (44%), tiredness (39%), forgetfulness (27%), dizziness (25%), neck pain (25%), and low back pain (19%). More than 50% of symptomatic persons reported more than 3 symptoms.

      Phase I cohort: health utilization

      By 6wk: MD (95%), PT (42%), DC (20%), and RMT (24.4%)

      By 1y: >90% were seeing MDs, but combinations of care were seen in the majority, especially MD-PT.
      McLean et al,
      • McLean S.A.
      • Kirsch N.L.
      • Tan-Schriner C.U.
      • et al.
      Health status, not head injury, predicts concussion symptoms after minor injury.
      2009; U.S.
      MTBI patients (n=251) from level II trauma center ED

      Patients (n=256) with minor injuries seen at the ED of a level II trauma center

      F/U: 1, 3, and 12mo
      Inclusion: patients aged ≥18y and presented within 24h of minor injury

      Exclusion: patients scoring below 19 on the Mini-Mental Status Examination or below 76 on the Galveston Orientation and Amnesia Test indicating current PTA; non-English speaking, prisoners, hospital transfers or admissions, clinically unstable, LOC ≥30min, or not competent to consent
      CDC criteria: GCS ≥13 on ED arrival and ≥1 of the following: (1) LOC ≤30min, (2) PTA, or (3) ≥2 PC symptoms (symptoms rated at least “mild” on RPSQ). Patients without direct head impact injury, but with LOC/PTA caused by trauma were classified as having MTBI if there was no other demonstrable cause for LOC.Prognostic factors: injury group, baseline mental and physical health measured by the SF-36 Mental Component (MnCS) and Physical Component Summary (PhCS) scales, initial postconcussion symptoms measured by the RPSQ, and type of injury (MTBI vs non-head injury)

      Outcomes: PCS defined ≥3 symptoms rated as at least mild on the RPSQ. SIP– Alertness Behavior (ab) subscale to evaluate cognitive symptom outcomes
      Compared with minor injury patients, MTBI patients had slightly worse mental (SF-36 MnCS 48 vs 51) and physical (SF-36 PhCS 50 vs 53) health. MTBI patients had more PC symptoms (RPSQ 13.9 vs 3.7) and had a higher incidence of PCS than other minor injuries (≈56% vs ≈28% at 1y postinjury).

      Phase II cohort: In the combined cohort of 507 patients, baseline MnCS and PhCS were associated with PCS and cognitive symptoms, but having an MTBI was not. PCS and cognitive symptoms are not specific to head injury.
      Stovner et al,
      • Stovner L.J.
      • Schrader H.
      • Mickeviciene D.
      • Surkiene D.
      • Sand T.
      Headache after concussion.
      2009; Lithuania
      Historic cohort: MTBI patients (n=131) admitted to emergency wards in a city

      Prospective cohort: MTBI patients (n=217) admitted to the same emergency wards in the city

      Patients (n=221) with orthopedic injuries not involving the head or neck admitted to the same emergency wards

      F/U: 3mo and 1y
      Inclusion:

      Historical cohort: age 18–67y admitted to emergency wards 22–35mo before the study

      Prospective cohort: age 18–60y for MTBI patients

      Historical and prospective cohort: orthopedic injury patients were age and sex matched to the MTBI patients.

      Exclusion: orthopedic controls with head or neck injury
      Head trauma with LOC <15minPrognostic factor: MTBI vs orthopedic injury

      Outcomes: prevalence of PTHA measured by ICHD-2 criteria and headache severity on a visual analog scale
      Phase II historical cohort: All MTBI patients presented with PTHA, but 92% had recovered by 1wk postinjury and 96% after 1mo. The prevalence of PTHA was similar between head-injured and non–head-injured patients, but MTBI patients complained of more photophobia than those with other injuries (41% vs 30%).

      Phase II prospective cohort: no significant difference in the prevalence of PTHA between MTBI and non–head-injured patients at 3mo and 1y. Fewer MTBI patients than orthopedic-injured patients had a history of headache before the trauma (44% vs 72%). The prevalence of persistent headache (ie, >15d/mo) in MTBI patients was similar to that in other patients at 3mo and 1y (16% vs 10% and 12% vs 13%, respectively).

      No important differences among groups were found in headache diagnosis, frequency, or symptoms at 1y after trauma, except photophobia was more prevalent in concussed patients.

      Headache occurring ≥3mo after injury is unlikely caused by brain injury.
      Abbreviations: CDC, Centers for Disease Control and Prevention; CES-D, Center for Epidemiologic Studies Depression Scale; CI, confidence interval; CT, computed tomography; DC, doctor of chiropractic; GHQ-12, General Health Questionnaire-12; HRR, hazard rate ratio; ICHD-2, International Classification of Headache Disorders. 2nd Edition; IES, Impact of Event Scale; ISS, Injury Severity Score; MD, medical doctor; MnCS, Mental Component Summary; MVC, motor vehicle collision; NRS, numeric rating scale; PC, postconcussion; PhCS, Physical Component Summary; PT, physical therapist; RMT, registered massage therapist; RNL, Reintegration to Normal Living Index; SIP, Sickness Impact Profile; U.S., United States.
      Two studies report on a population-based cohort of MTBI after traffic collisions from the Canadian province of Saskatchewan. Cassidy et al
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      found that the median time to self-reported recovery was 100 days in this cohort, and about 23% reported not being recovered by 1 year. Hartvigsen et al
      • Hartvigsen J.
      • Boyle E.
      • Cassidy J.D.
      • Carroll L.J.
      Mild traumatic brain injury after motor vehicle collisions: what are the symptoms and who treats them? A population-based 1-year inception cohort study.
      found that the most common symptoms reported by those not recovered at 1 year were sleep disturbances (44%), tiredness (39%), forgetfulness (27%), dizziness (25%), neck pain (25%), and low back pain (19%). Some of these symptoms might be due to coexisting whiplash injuries to the spine. They also reported that more than 50% of these symptomatic participants reported more than 3 symptoms. Most who continued to seek care for their symptoms at 1 year postinjury were seeing medical doctors, although a substantial number were also seeking care from physical therapists, registered massage therapists, and chiropractors. In a phase II analysis of prognostic factors from the same cohort, Cassidy
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      found that prolonged recovery was associated with age >50 years, less education, poor expectations for recovery, depressive symptomatology, hearing problems, arm numbness, confusion, headache intensity, low back pain intensity, and mid-back pain intensity. Sex, LOC, and PTA were not associated with recovery. Overall, these results suggest that traffic-related MTBI occurs with other injuries to the neck and back, and expectation for recovery, depression, and somatic complaints determine the outcome.
      The remaining 4 studies all had control groups to compare to patients with MTBI recruited from emergency departments (EDs). One phase III prognostic study
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      focused on fatigue and compared 173 patients with MTBI and no PTA or LOC, with 58 patients with LOC ≤30 minutes and/or PTA <24 hours and 128 patients with other mild nonhead injuries. By 1-year follow up, levels of fatigue were slightly higher in the group with MTBI and no LOC or PTA, but all groups were still within population norms indicating low levels of fatigue. Worse fatigue at 1-year follow up was associated with preinjury fatigue, marital status, lawyer involvement, and baseline poor medical and mental health, but not with type of injury. These results confirm that postinjury fatigue is no worse in MTBI than in other injuries and is associated with psychosocial factors.
      Using the same injury cohort as de Leon et al,
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      McLean et al
      • McLean S.A.
      • Kirsch N.L.
      • Tan-Schriner C.U.
      • et al.
      Health status, not head injury, predicts concussion symptoms after minor injury.
      examined prognostic factors associated with persistent PCS 1 year after injury. They compared 251 patients with MTBI to 256 patients with minor nonhead injuries. Outcomes included PCS defined as ≥3 symptoms rated as at least mild on the RPSQ, mental and physical health measured by the SF-36, and level of cognitive symptoms measured by the Sickness Impact Profile–Alertness Behavior subscale. Compared with non–head-injured patients, those with MTBI had slightly worse mental and physical health at 1 year. They also reported more postconcussion symptoms (RPSQ, 13.9 vs 3.7) and had a higher incidence of PCS (≈56% vs ≈28%) at 1 year postinjury. In the combined cohort of 507 patients, baseline mental and physical health was associated with PCS and cognitive symptoms, but having an MTBI was not. The findings of this phase II study are in agreement with those of previous studies with short-term outcomes that suggest that the development of PCS and cognitive symptoms are not specific to head injury. In another study, Friedland and Dawson
      • Friedland J.F.
      • Dawson D.R.
      Function after motor vehicle accidents: a prospective study of mild head injury and posttraumatic stress.
      came to a similar conclusion after comparing 64 patients with MTBI to 35 non–head-injured patients and following them up to between 6 and 9 months postinjury. In this phase I study, patients with symptoms of posttraumatic stress did not do well in terms of functional outcome regardless of injury type. The patients with MTBI were not particularly worse off compared with those with other injuries, but they did have lower psychosocial scores on the Sickness Impact Profile but no other significant difference on outcomes.
      Finally, Stovner et al
      • Stovner L.J.
      • Schrader H.
      • Mickeviciene D.
      • Surkiene D.
      • Sand T.
      Headache after concussion.
      used historical and prospective cohort designs to measure the prevalence of PTHA in patients with MTBI and patients with orthopedic injuries. Both studies indicate that PTHA prevalence is similar in patients with MTBI and in orthopedic-injured patients. In the historical cohort, more than 90% of all patients had recovered from their PTHA by 1 month. In the prospective cohort, 10% of patients with MTBI and 12% of orthopedic-injured patients complained of persistent headache (ie, >15d/mo) after 1 year. Although photophobia was more common in patients with MTBI, there were no other differences among groups with respect to frequency or types of symptoms at 1 year. The authors conclude that headache occurring more than 3 months after MTBI is unlikely caused by brain injury per se. The results of this phase II study should be interpreted with caution, since other authors have found a very low rate of expectation of any chronic sequelae after MTBI in Lithuania.
      • Ferrari R.
      • Obelieniene D.
      • Russell A.S.
      • Darlington P.
      • Gervais R.
      • Green P.
      Symptom expectation after minor head injury. A comparative study between Canada and Lithuania.
      These results suggest that PTHA is not a problem in Lithuania after MTBI, but studies from other jurisdictions do not necessarily agree.

      More than 1-year follow up

      We accepted 2 phase II cohort studies
      • Ozen L.J.
      • Fernandes M.A.
      Effects of “diagnosis threat” on cognitive and affective functioning long after mild head injury.
      • Iverson G.L.
      • Lange R.T.
      Examination of “postconcussion-like” symptoms in a healthy sample.
      and 1 nonrandomized experimental study
      • Ozen L.J.
      • Fernandes M.A.
      Effects of “diagnosis threat” on cognitive and affective functioning long after mild head injury.
      with follow up for more than 1 year postinjury, including 1 study each from Brazil, Canada, and Sweden (table 5). Outcomes included postconcussion symptoms measured by the RPSQ, health-related quality of life, anxiety, depression, self-reported cognitive function, self-reported memory, fatigue, sleep disturbance, and loneliness.
      Table 5Studies of self-reported outcomes in adults with more than 1 year of follow up
      Author, Year, CountrySource Population, Study Size, Participation, F/UInclusion/Exclusion CriteriaMTBI Case DefinitionPrognostic Factors/Self-Reported OutcomesFindings
      de Almeida Lima et al,
      • De Almeida Lima D.P.
      • Filho C.S.
      • de Campos Vieira Abib S.
      • Poli de Figueiredo L.F.
      Quality of life and neuropsychological changes in mild head trauma. Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission.
      2008; Brazil
      MTBI patients (n=39) treated at a hospital ED of a trauma center

      Household controls (n=39)

      F/U: 18mo
      Cases had isolated head trauma treated at an ED trauma center from September to October 2004.

      Controls lived in the same household as patients and had no history of head trauma and had to preferably be of the same sex and similar age.
      GCS 13–15 and at least 1 of the following symptoms at admission to the ED: headache, vertigo, amnesia, nausea, vomiting, or LOC <15minPrognostic factor: S100B protein levels and injury status

      Outcomes: PC symptoms (RPSQ), HRQL (SF-36), anxiety and depression (HADS)
      No correlation between S100B protein levels at ED visit and positive CT scan or with HRQL, anxiety, or depression at 18-mo F/U

      Phase II cohort: Patients had worse SF-36 domain scores of functional capacity, pain, vitality, social aspects, and mental health compared with controls. Patients complained of more depression and anxiety than controls (47% vs 22% for anxiety; 25% vs 11% for depression). Compared with controls, patients complained of more loss of balance (42.1% vs 20%), dry mouth (44.7% vs 20%), arm pain (39.5% vs 11.4%), loss of memory (36.8% vs 14.3%), and dizziness (60.5% vs 37.1%).
      Ozen and Fernandes,
      • Ozen L.J.
      • Fernandes M.A.
      Effects of “diagnosis threat” on cognitive and affective functioning long after mild head injury.
      2011; Canada
      Participants: university students (n=87) assigned to 2 groups:

      1. Diagnosis threat group (n=43): informed that study to examine negative effects of head injury on cognitive functioning. Included 22 with past MTBI and 21 with no history of MTBI.

      2. Neutral group (n=44): unaware of effects of MTBI on cognitive functioning. Included 21 with past MTBI and 23 with no history of MTBI

      Variable F/U: on average, 5.1–7.5y after injury
      Inclusion: healthy students fluent in English with normal or corrected-to-normal hearing and vision

      Exclusion: past diagnosis of psychological or neurologic disorder, or diagnosis of depression or anxiety
      Any strike to the head or acceleration/deceleration whiplash force that resulted in LOC and occurred at least 6mo before the study testing. Severity was determined by duration of LOC, PTA, disorientation, and/or confusion. MTBI was defined by PTA <24h and LOC ≤30min.Prognostic factors: symptom expectation—diagnosis threat group vs neutral group

      Outcomes:

      self-reported depression (BDI), anxiety (STAI), cognitive errors (ARCES), and memory failures (MFS)
      Nonrandomized experiment: Diagnosis threat group with past MTBI reported more cognitive errors and memory failures than all others. Neutral group with past MTBI reported more anxiety than others. No other significant differences detected between groups. These results suggest that expectations influence self-reported cognitive and memory results.
      Sundström et al,
      • Sundström A.
      • Nilsson L.G.
      • Cruts M.
      • Adolfsson R.
      • Van Broeckhoven C.
      • Nyberg L.
      Fatigue before and after mild traumatic brain injury: pre-post-injury comparisons in relation to apolipoprotein E.
      2007; Sweden
      Random sample of adults from a population registry in northern Sweden forming the Betula Longitudinal Cohort on Aging

      MTBI (n=31)

      Age-, sex-, education-, and APOE-matched controls (n=62)

      F/U: every 5y (minimum 10y of F/U)
      Inclusion: age 35–85y and past MTBI. For each MTBI, 2 non–head-injured controls were chosen matched for age, sex, education, and APOE genotype.

      Exclusion: psychiatric illness, memory disturbance, stroke, brain infection, neurologic disorders, Mini-Mental State Examination scores <23, subjects with missing data, and developing dementia cases
      MTBI: self-reported to have met the American Congress of Rehabilitation Medicine criteriaPrognostic factors: injury status (MTBI vs control) and presence of APOE ε4 genotype.

      Outcome: single questions about the presence of fatigue, anxiety, sleep disturbance, loneliness, and depression
      Compared with preinjury, those with MTBI had more fatigue (16.1% vs 41.9%). There was no increase in fatigue in the control group over time.

      Phase II cohort: Postinjury fatigue was more common in MTBI cases with APOE ɛ4 (58% vs 32%). Among carriers of APOE ɛ4, those with MTBI had more fatigue than those without (58% vs 17%). No significant differences in other outcomes.
      Abbreviations: APOE, apolipoprotein E; ARCES, Attention-Related Cognitive Error Score; BDI, Beck Depression Inventory; CT, computed tomography; F/U, follow up; HADS, Hospital Anxiety and Depression Scale; HRQL, health-related quality of life; MFS, Memory Failures Scale; PC, postconcussion; STAI, State-Trait Anxiety Inventory.
      The 2 phase II studies included uninjured controls to look at the prognostic value of S100B
      • De Almeida Lima D.P.
      • Filho C.S.
      • de Campos Vieira Abib S.
      • Poli de Figueiredo L.F.
      Quality of life and neuropsychological changes in mild head trauma. Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission.
      and the apolipoprotein E (APOE) ε4 genotype.
      • Sundström A.
      • Nilsson L.G.
      • Cruts M.
      • Adolfsson R.
      • Van Broeckhoven C.
      • Nyberg L.
      Fatigue before and after mild traumatic brain injury: pre-post-injury comparisons in relation to apolipoprotein E.
      De Almeida Lima et al
      • De Almeida Lima D.P.
      • Filho C.S.
      • de Campos Vieira Abib S.
      • Poli de Figueiredo L.F.
      Quality of life and neuropsychological changes in mild head trauma. Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission.
      followed up 38 cases of MTBI treated at an ED for 18 months and compared them with 39 household controls. They found no correlation between S100B protein levels and abnormal findings on a computed tomography scan, or between S100B and health-related quality of life or depression at follow up, confirming the results of Nygren-de Boussard et al
      • Nygren-de Boussard C.
      • Lundin A.
      • Karlstedt D.
      • Edman G.
      • Bartfai A.
      • Borg J.
      S100 and cognitive impairment after mild traumatic brain injury.
      that S100B is not a useful prognostic marker in patients with MTBI. Sundström et al
      • Sundström A.
      • Nilsson L.G.
      • Cruts M.
      • Adolfsson R.
      • Van Broeckhoven C.
      • Nyberg L.
      Fatigue before and after mild traumatic brain injury: pre-post-injury comparisons in relation to apolipoprotein E.
      looked at the prognostic value of APOE in 31 patients with MTBI and compared them with matched controls. Outcomes included simple questions about various postconcussion symptoms. Postinjury fatigue was more common in MTBI cases with APOE ε4 than without it (58% vs 32%). Among carriers of APOE ε4, those with MTBI had more fatigue than controls without MTBI (58% vs 17%). These results are preliminary and need to be confirmed in a phase III study.
      Finally, Ozen and Fernandes
      • Ozen L.J.
      • Fernandes M.A.
      Effects of “diagnosis threat” on cognitive and affective functioning long after mild head injury.
      conducted a nonrandomized experiment with undergraduate university students to determine whether expectations of MTBI symptoms influence self-reported symptoms. Students were initially surveyed about past head injuries, and then a subset of those with and without head injury were surveyed again under 2 separate scenarios. Under a “diagnosis threat” scenario, 22 students with and 21 students without past head injury were tested with the knowledge that the tests were focused on comparing outcomes between those with and without past MTBI. Under the “neutral” scenario, 21 students with and 23 students without past head injury were tested without knowledge that the tests were focused on past MTBI status. The diagnosis threat group with past MTBI reported more cognitive errors and memory failures than all others. The neutral scenario group with past MTBI reported more anxiety than others. These results suggest that expectations influence self-reported cognitive and memory results.

      Discussion

      Our results support the previous finding of the WHO Collaborating Centre Task Force on MTBI that self-reported symptoms such as headache, fatigue, self-perceived cognitive deficits and other so-called postconcussion symptoms are common in the acute stage of injury but are not specific to MTBI.
      • Carroll L.J.
      • Cassidy J.D.
      • Peloso P.M.
      • et al.
      Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
      When compared with uninjured controls, patients with MTBI do report more postconcussion symptoms at 3 months
      • Kashluba S.
      • Paniak C.
      • Blake T.
      • Reynolds S.
      • Toller-Lobe G.
      • Nagy J.
      A longitudinal, controlled study of patient complaints following treated mild traumatic brain injury.
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      and at 1 year.
      • De Almeida Lima D.P.
      • Filho C.S.
      • de Campos Vieira Abib S.
      • Poli de Figueiredo L.F.
      Quality of life and neuropsychological changes in mild head trauma. Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission.
      • Sundström A.
      • Nilsson L.G.
      • Cruts M.
      • Adolfsson R.
      • Van Broeckhoven C.
      • Nyberg L.
      Fatigue before and after mild traumatic brain injury: pre-post-injury comparisons in relation to apolipoprotein E.
      However, postconcussion symptoms are equally prevalent in those with other nonhead injuries.
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      • Rush B.K.
      • Malec J.F.
      • Moessner A.M.
      • Brown A.W.
      Preinjury personality traits and the prediction of early neurobehavioral symptoms following mild traumatic brain injury.
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Friedland J.F.
      • Dawson D.R.
      Function after motor vehicle accidents: a prospective study of mild head injury and posttraumatic stress.
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      • Stovner L.J.
      • Schrader H.
      • Mickeviciene D.
      • Surkiene D.
      • Sand T.
      Headache after concussion.
      Most of the postconcussion symptoms could be viewed as common reactions to the stress of injury, or other mental or physical health stressors. For example, Landre et al
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      showed that acute postconcussion symptoms are associated with emotional distress, but not type of injury. De Leon et al
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      found that fatigue severity at 1-year follow up was associated with baseline fatigue, past mental health issues, past medical disability, marital status, and being involved in litigation, but not the type of injury (ie, MTBI vs nonhead injury). All this evidence calls into question the validity of the PCS as a specific diagnosis and sequelae of MTBI. These symptoms are common in the general population,
      • Iverson G.L.
      • Lange R.T.
      Examination of “postconcussion-like” symptoms in a healthy sample.
      in patients with chronic pain,
      • McCracken L.M.
      • Iverson G.L.
      Predicting complaints of impaired cognitive functioning in patients with chronic pain.
      and after whiplash injury to the neck.
      • Merrick D.
      • Stålnacke B.-M.
      Five years post whiplash injury: symptoms and psychological factors in recovered versus non-recovered.
      • Ferrari R.
      • Russell A.S.
      • Carroll L.J.
      • Cassidy J.D.
      A re-examination of the whiplash associated disorders (WAD) as a systemic illness.
      In addition, 2 studies
      • Davis C.H.
      Self-perception in mild traumatic brain injury.
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      we reviewed show that patients with MTBI tend to minimize symptoms that they have before being injured. Thus, we recommend that the term postconcussion syndrome be replaced with posttraumatic symptoms because they are common to all injuries.
      Even though posttraumatic symptoms are not specific to MTBI, they are a problem for patients and clinicians. The literature reviewed by the WHO Collaborating Centre Task Force suggested that most patients recover within 3 months to 1 year.
      • Carroll L.J.
      • Cassidy J.D.
      • Peloso P.M.
      • et al.
      Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
      Our update supports this, but there is evidence that a significant minority continue to have subjective complaints. Hou et al
      • Hou R.
      • Moss-Morris R.
      • Peveler R.
      • Mogg K.
      • Bradley B.P.
      • Belli A.
      When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.
      found that 22% of patients had 3 or more posttraumatic symptoms at 3 months, and there was no significant recovery by 6 months. Norrie et al
      • Norrie J.
      • Heitger M.
      • Leathem J.
      • Anderson T.
      • Jones R.
      • Flett R.
      Mild traumatic brain injury and fatigue: a prospective longitudinal study.
      found that 30% of patients complained of fatigue at 3 months, and this remained relatively stable at 26% by 6 months. Stulemeijer et al
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      found that 36% of patients with MTBI continued to have 3 or more posttraumatic symptoms at 6 months. Cassidy et al
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      reported that the median time to self-reported recovery was 100 days in patients with MTBI after traffic collisions, and that about 23% report not being recovered by 1 year. However, these same studies show that persistent posttraumatic symptoms are associated with psychosocial factors such as depression,
      • Norrie J.
      • Heitger M.
      • Leathem J.
      • Anderson T.
      • Jones R.
      • Flett R.
      Mild traumatic brain injury and fatigue: a prospective longitudinal study.
      posttraumatic stress,
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      negative injury perceptions,
      • Hou R.
      • Moss-Morris R.
      • Peveler R.
      • Mogg K.
      • Bradley B.P.
      • Belli A.
      When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.
      and poor expectations for recovery.
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      Other psychosocial factors associated with posttraumatic symptoms at follow up include mental health status,
      • Landre N.
      • Poppe C.J.
      • Davis N.
      • Schmaus B.
      • Hobbs S.E.
      Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      • McLean S.A.
      • Kirsch N.L.
      • Tan-Schriner C.U.
      • et al.
      Health status, not head injury, predicts concussion symptoms after minor injury.
      anxiety in women,
      • Dischinger P.C.
      • Ryb G.E.
      • Kufera J.A.
      • Auman K.M.
      Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.
      and litigation or lawyer involvement.
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the “good-old-days” bias following mild traumatic brain injury.
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      In fact, these psychosocial factors are more strongly associated with outcomes than the traditional biomedical factors thought to determine recovery. For example, several studies
      • Cassidy J.D.
      • Boyle E.
      • Carroll L.J.
      Population-based, inception cohort study of the incidence, course, and prognosis of mild traumatic brain injury after motor vehicle collisions.
      • Hou R.
      • Moss-Morris R.
      • Peveler R.
      • Mogg K.
      • Bradley B.P.
      • Belli A.
      When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      • de Leon M.B.
      • Kirsch N.L.
      • Maio R.F.
      • et al.
      Baseline predictors of fatigue 1 year after mild head injury.
      found that LOC and PTA were not associated with recovery from self-reported symptoms. The results of our review suggest that patients with persistent posttraumatic symptoms might benefit from psychosocial interventions, and this should be a focus of future intervention studies.
      One purpose of prognosis is the early recognition of patients at risk of a poor or good outcome. Clinical prediction rules are prognostic tools that can help stratify patients into different risk sets at the onset of a disorder and can inform the clinician and patient of the likely course of recovery and aid in treatment decisions.
      • Royston P.
      • Moons K.G.
      • Altman D.G.
      • Vergouwe Y.
      Prognosis and prognostic research: developing a prognostic model.
      Our review found 1 clinical prediction rule. Stulemeijer
      • Stulemeijer M.
      • van der Werf S.
      • Borm G.F.
      • Vos P.E.
      Early prediction of favourable recovery 6 months after mild traumatic brain injury.
      developed a clinical prediction rule in patients admitted to the ED with MTBI in The Netherlands. They defined a good outcome as a score of less than 3 on at least 13 of 16 posttraumatic symptoms measured by the RPSQ. An absence of comorbid physical problems, low levels of early posttraumatic symptoms, and low levels of early posttraumatic stress predicted a good outcome at 6 months with a probability of 90%. However, these results need to be validated in another setting before being recommended for widespread use.

      Study limitations and strengths

      Our study has some limitations and strengths. Although we followed a strict PRISMA-compliant protocol, our conclusions are only as good as the literature that we have accepted, and we found it to be generally weak and heterogeneous. Of the 173 studies we reviewed on adult prognosis of MTBI, only 51 (29%) were considered to have a low risk of bias, and 21 of these included self-reported outcomes relevant to this article. It is disappointing that so few good prognostic studies have been published since the WHO Task Force reviewed the same literature up to the year 2000. Also, only 1 of our accepted articles was a phase III confirmatory prognostic study. However, we may have excluded some good studies that included intentional injuries, or included both adults and children without stratifying the results. We a priori decided to do this because we think children and those with intentional injuries may have a different trajectory for recovery. In addition, most of the prognostic studies we reviewed did not take into account potential confounding effects of varying levels of treatment on prognosis. However, since there is little evidence of treatment effectiveness in MTBI, we do not think this is a major problem.
      • Nygren-de Boussard C.
      • Holm L.W.
      • Cancelliere C.
      • et al.
      Nonsurgical interventions after mild traumatic brain injury: a systematic review. Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      Although our search strategy was comprehensive, we may have missed some good studies that were not in the searched databases or not in languages included in our protocol.
      A strength of the ICoMP is that our group includes a mix of methodological and clinical scientists with a spectrum of experience in systematic reviews and clinical care of MTBI. Our group also carefully considered the strength of the evidence on MTBI prognosis and report only on studies that have a low risk of bias. Thus, our results include only the best current evidence.

      Conclusions

      Since the prognosis review of the WHO Collaborating Centre Task Force, there has been some progress in understanding MTBI prognosis. Our results add to the growing evidence that postconcussion symptoms are not specific to MTBI and occur commonly in the general population and after other nonhead injuries. Our results also confirm the importance of psychosocial determinants of recovery. We conclude that self-reported symptoms can be persistent after MTBI, and there is a need for more intervention research targeting modifiable prognostic factors. Finally, we found only 1 study of a clinical prediction rule, and we recommend more focus on this issue because it holds the potential of identifying those at risk of a poor recovery who might benefit from more focused clinical attention.

      Acknowledgments

      We thank the other members of ICoMP—Jean-Luc af Giejerstam, MD, PhD; Eleanor Boyle, PhD; Victor G. Coronado, MD, MPH; Alison K. Godbolt, MBChB, MD; Ryan Hung, MD, MSc; Michelle Keightley, PhD; Alvin Li, BHSc; Connie Marras, MD, PhD; Peter Rumney, MD; and Britt-Marie Stålnacke, MD, PhD—for their contribution to this work; Panos Lambiris, MSc, Information Scientist, University Health Network, for assisting in developing, testing, and updating the search strategies; and Meijia Zhou, BSc, for assistance with retrieving and screening articles.

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