Archives of Physical Medicine and Rehabilitation journal homepage: www.archives-pmr.org Archives of Physical Medicine and Rehabilitation 2014;95(3 Suppl 2):S152-73
REVIEW ARTICLE
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 Linda J. Carroll, PhD,a J. David Cassidy, PhD, DrMedSc,b,c,d,e Carol Cancelliere, DC, MPH,b,c Pierre Coˆte´, DC, PhD,c,e,f Cesar A. Hincapie´, DC, MHSc,b,e Vicki L. Kristman, PhD,e,g,h,i Lena W. Holm, DrMedSc,j Jo¨rgen Borg, MD, PhD,k Catharina Nygren-de Boussard, MD, PhD,k Jan Hartvigsen, PhDd,l From the aSchool of Public Health and Alberta Centre for Injury Control and Research, University of Alberta, Edmonton, Canada; bDivision of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada; cInstitute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; dInstitute of Sports Science and Clinical Biomechanics, Faculty of Health, University of Southern Denmark, Odense, Denmark; eDivision of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; fFaculty of Health Sciences, University of Ontario Institute of TechnologyCanadian Memorial Chiropractic College Centre for the Study of Disability Prevention and Rehabilitation, Toronto, Ontario, Canada; g Department of Health Sciences, Lakehead University, Thunder Bay, Ontario, Canada; hInstitute of Work and Health, Toronto, Ontario, Canada; i Division of Human Sciences, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada; jDivision of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; kDepartment of Clinical Sciences, Rehabilitation Medicine, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden; and lNordic Institute of Chiropractic and Clinical Biomechanics, Odense, Denmark.
Abstract Objective: To synthesize the best available evidence on objective outcomes after adult mild traumatic brain injury (MTBI). Data Sources: MEDLINE and other databases were searched (2001e2012) for studies related to MTBI. Inclusion criteria included published, peer-reviewed articles in English and other languages. References were also identified from the bibliographies of eligible articles. Study Selection: Randomized controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI cases and assess objective outcomes in adults. Data Extraction: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables. Data Synthesis: Evidence was synthesized qualitatively according to modified SIGN criteria, and studies were categorized as exploratory or confirmatory based on the strength of their design and evidence. After 77,914 records were screened, 299 were found to be relevant and critically reviewed, and 101 were deemed scientifically admissible. Of these, 21 studies that were related to the objective outcomes form the basis of this review. Most evidence indicates the presence of cognitive deficits in the first 2 weeks post-MTBI, and some evidence suggests that
Supported by the Ontario Neurotrauma Foundation (grant no. 2010-ABI-MTBIWHO-871). The funder was not involved in the design or preparation of the study protocol, or in the management of the project, analysis or interpretation of data, or the preparation of the final article. No commercial party having a direct financial interest in the results of the research supporting this article has conferred or will confer a benefit on the authors or on any organization with which the authors are associated. The findings and conclusions in this research are those of the authors alone and do not necessarily represent the official views or policies of the Centers for Disease Control and Prevention or any agency of the United States government. Inclusion of individuals, programs, or organizations in this article does not constitute endorsement by the United States government.
0003-9993/14/$36 - see front matter ª 2014 by the American Congress of Rehabilitation Medicine http://dx.doi.org/10.1016/j.apmr.2013.08.300
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complete recovery may take 6 months or a year. A small number of studies indicate that MTBI increases the risk of psychiatric illnesses and suicide. Conclusions: Early cognitive deficits are common, and complete recovery may be prolonged. Conclusions about mortality post-MTBI are limited. This review has implications for expected recovery after MTBI and MTBI-related health sequelae. Well-designed confirmatory studies are needed to understand the medium- to long-term consequences of MTBI and to further evaluate the effect of prior MTBI and injury severity on recovery. Archives of Physical Medicine and Rehabilitation 2014;95(3 Suppl 2):S152-73 ª 2014 by the American Congress of Rehabilitation Medicine
Mild traumatic brain injury (MTBI) or concussion is common in the general population. A previous review on the incidence of MTBI estimated that there are 100 to 300 hospital-treated cases of MTBI per 100,000 persons per year. However, this is likely the tip of the iceberg because there is evidence that much MTBI is not treated at hospitals.1 The main causes of MTBI are falls and motor vehicle collisions, and MTBI is a condition that disproportionately affects the young (teenagers and young adults) and is more common in men than women.1 Given its frequency, having good information on the course of recovery and predictors of recovery is a priority. There have been several systematic reviews examining the presence of cognitive outcomes after MTBI. One of these (published in 2003) reports2 a meta-analysis showing a moderate effect of MTBI on cognitive functioning in the early stages of recovery. Although that review was not designed to track the course of recovery after MTBI (which requires studies with a longitudinal design), the authors extrapolated from mostly cross-sectional studies that, on average, cognitive recovery appears to occur within the first 3 months. A subsequent systematic review3 examined the presence of long-term MTBI-related cognitive impairment (>6mo), and reported that there was insufficient evidence to come to a conclusion. The aim of the current article is to expand and update our knowledge about the presence and course of recovery of MTBIrelated cognitive impairment in adults and prognostic factors for that recovery and to report other objectively measured outcomes of MTBI. A previous systematic review4 (a best evidence synthesis) on the course and prognostic factors for MTBI recovery was published in 2004 by the World Health Organization (WHO) Collaborating Centre Task Force on MTBI. To inform about the course of recovery and prognostic factors for recovery, studies must use a longitudinal design. In the 2004 review,4 only 9 longitudinal studies reporting on cognitive deficits in adults after nonesports-related MTBI were sufficiently methodologically sound to be included in the best evidence synthesis. The limited information available at the time suggested the presence of initial cognitive deficits, but generally good recovery of cognitive functioning. However, the paucity of studies limited the authors’ confidence in this conclusion, leaving questions about how long cognitive recovery typically takes in adults and what preinjury or initial postinjury factors predicted good versus poor cognitive recovery. The review4,5 suggested that much of the research on prognosis in adults was methodologically weak. In particular, the review called for more attention to the control of confounding and to selection of control groups. Specifically, investigators designing research were called on to consider the question of whether factors (eg, pain, medications, psychological distress, and other potential confounders) have an impact on assessment of cognitive functioning of adults with MTBI. Moreover, challenges faced by researchers in interpreting neuropsychological test scores have been
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outlined by Iverson and Gaetz,6 among others. Iverson and Gaetz6 point out that intertest score scatter occurs even in the healthy population, and the more tests are administered, the greater the likelihood that an individual will score in the extreme range, even in the absence of a brain dysfunction. Therefore, cautious interpretation of study findings is warranted. Since the above review was published in 2004, there has been a good deal of research activity in MTBI, and the current update of the WHO Collaborating Centre Task Force was undertaken by an international group of researchers and clinicians, the International Collaboration on MTBI Prognosis (ICoMP). The ICoMP conducted a systematic search, critical review, and best evidence synthesis of the research on MTBI prognosis published since the work of the WHO Collaborating Centre Task Force on MTBI. The current article forms a part of this endeavor and reports on those studies concerned with presence, course of recovery, and predictors of recovery of cognitive outcomes (assessed by neuropsychological measures); psychiatric outcomes of MTBI; mortality outcomes associated with MTBI; and other objectively assessed outcomes in adults subsequent to nonesports-related and nonemilitary-related MTBI.
Methods The protocol registration, case definition, literature search, critical review strategy, and data synthesis are outlined in detail elsewhere7 and in this issue.8 Briefly, the electronic databases MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were systematically searched from 2001 to 2012. Reference lists of all systematic reviews and meta-analyses related to MTBI and all articles meeting the eligibility criteria were checked to ensure that relevant studies were not missed. Articles were screened according to predefined criteria. Inclusion criteria included original, published peer-reviewed research reports in English, French, Swedish, Norwegian, Danish, and Spanish; human participants of all ages; and a minimum of 30 participants with MTBI or concussion. The definition of MTBI had to be consistent (but not necessarily identical) with the definitions provided by the WHO Collaborating Centre Task Force on MTBI5 and the Centers for Disease Control and Prevention.9 Eligible study designs were randomized controlled trials with prognostic information, cohort studies, and case-control studies. Exclusion criteria included cross-sectional studies, case reports, case series, and cadaveric, biomechanical, and laboratory studies. Eligible articles were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria.10 Two reviewers performed independent, in-depth reviews of each eligible study, and a third reviewer was consulted for disagreements. ICoMP members also undertook 3 original
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research projects, one of which is included in this review. These studies were critically appraised by the ICoMP members not involved in their conduct. Data from accepted articles were independently extracted into evidence tables by 2 reviewers, and the evidence was synthesized according to the modified SIGN criteria. A best evidence synthesis was performed to provide conclusions based on the best available evidence. We also synthesized the evidence using the phases of study framework described by Coˆte´ et al11 (table 1). The strongest evidence is found in phase III studies, followed by phase II studies. Phase I studies do not consider confounding and are weaker evidence. Our findings were synthesized separately for cognitive, psychiatric, mortality, and other outcomes in adults with MTBI.
Results Out of 77,914 records screened for our entire review, 2170 fulltext articles were assessed for eligibility, 299 were critically reviewed, and 101 (ie, 34%) were deemed scientifically admissible (fig 1). This article presents the 21 accepted studies (all were published in English) reporting findings on course and prognostic factors associated with neuropsychological findings, psychiatric disorders, suicide subsequent to MTBI, mortality outcomes, and other objective outcomes. These studies form the basis of our best evidence synthesis. The findings are divided into 4 sections: neuropsychological outcomes (table 2), psychiatric outcomes (including suicide) (table 3), other articles reporting on mortality after MTBI (table 4), and other outcomes (table 5).
Neuropsychological outcomes Twelve articles addressed cognitive outcomes of MTBI using cognitive testing (ie, not self-report) (table 2). Two are randomized controlled trials conducted in the U.S.,12,13 1 is a nonrandomized experiment conducted in Canada,14 7 are phase II cohort studies conducted in Israel, New Zealand, Canada, the U.S., Sweden, and India,15-20,23 and 2 are phase I cohort studies conducted in the U.S. and Canada.21,22 Sampling frames were varied: admissions to emergency departments,18,19,21,22 inpatient admissions,15,17 trauma database,16 undergraduate students,12-14 a population-based study,23 and unreported.20 Only 2 studies used repeated testing, which involved tracking cognitive recovery at 48 hours and 1 month in one study,21 and at 2 weeks and 3, 6, and 12 months in the other.19 Comparisons were made with test norms, healthy controls, control group made up of non-TBI injured persons, and preinjury test scores. Finally, 3 studies compared neuropsychological findings under experimentally induced testing conditions, thereby experimentally manipulating the prognostic factor of interest.12-14
List of abbreviations: APOE CT GCS ICoMP LOC MTBI PTA SIGN TBI WHO
apolipoprotein E computed tomography Glasgow Coma Scale International Collaboration on MTBI Prognosis loss of consciousness mild traumatic brain injury posttraumatic amnesia Scottish Intercollegiate Guidelines Network traumatic brain injury World Health Organization
Table 1
Phases of prognostic studies framework
Study Phase Description Phase I
Phase II
Phase III
Hypothesis-generating investigations exploring the associations between potential prognostic factors and health outcomes in a descriptive or univariable way Extensive exploratory analyses focusing on particular sets of prognostic factors, or attempting to discover which factors have the highest prognostic value Large confirmatory studies of explicit prestated hypotheses that allow for a focused examination of the strength, direction, and independence of the proposed relation between a prognostic factor and the outcome of interest
Presence of deficits within the first 2 weeks Five studies16,17,19,20,21 (1 phase I and 4 phase II studies) examined neuropsychological outcomes within the first 2 weeks after injury, with comparisons of test scores of people with MTBI against test normative data, uninjured samples, and individuals with injuries other than TBI. Study findings are as follows. Brewer et al21 studied emergency department admissions for MTBI with loss of consciousness (LOC) of 10 minutes (phase I study). At 48 hours postinjury, there were no deficits in tests of executive functioning, but patients were distractible. Another study17 (phase II) also found MTBI-related distractibility at 4 to 5 days postinjury. That study assessed a sample of patients with and without MTBI, all hospitalized because of their injuries. People with MTBI had Glasgow Coma Scale (GCS) scores of 14 or 15, and were mostly hospitalized because of concurrent injuries, rather than the traumatic brain injury (TBI) itself. In addition to increased distractibility, the Landre et al17 study also found the MTBI group to have deficits in attention and memory compared with the injured non-TBI control group. This design potentially controls for the impact of an injury itself on cognitive functioning, although in this study it is unclear whether the overall injury severity was comparable. Although there are challenges in comparing the severity of different types of injuries, it remains a potential confounder, which suggests caution in interpreting these findings. However, pain intensity and emotional distress were measured in both groups and were unassociated with test scores.17 Similarly, deficits in attention and learning/memory of simple and complex material at 2 weeks post-MTBI were also observed in a third study (phase II). In that study,20 people with MTBI were compared with uninjured age-, education-, and socioeconomic status-matched controls (friends or relatives of the participants). In the first assessment period of a 1-year longitudinal study, Heitger et al19 (phase II study, emergency department sample) also reported verbal learning deficits and speed of information processing deficits in people with MTBI compared with age-, sex-, and education-matched healthy controls from a volunteer database at 1 week postinjury. These findings are not entirely consistent with Brewer,21 who found slowed processing speed only in those with LOC, although there is no information in the Heitger19 study on percentage of participants with LOC. Brewer21 also reported impulsivity and deficits in directed attention only in those with LOC. Heitger19 found no MTBIrelated deficits in sustained or divided attention, information www.archives-pmr.org
Prognosis after mild traumatic brain injury: a review
Fig 1
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Flow diagram of literature search.
processing capacity, short-term and working memory, or general cognitive performance. Finally, Iverson16 compared patients with MTBI with and without computed tomography (CT) abnormalities (phase II study, whose data source was a trauma database). At 4 days postinjury, both groups showed deficits in comparison with test norms, although systematic differences between participants and the normative sample are possible. Patients with CT abnormalities performed more poorly on cognitive tests than those with normative CT; however, effect sizes were small to medium; therefore, the clinical importance of these differences is unclear. Moreover, Iverson16 reports that cognitive test findings did not differentiate those with and without CT abnormalities in a multivariable www.archives-pmr.org
statistical model. Iverson16 concluded that the performance of the 2 groups (those with and without CT abnormalities) was more similar than dissimilar. In summary, there were consistent findings that MTBI is associated with cognitive deficits between 48 hours and 2 weeks post-MTBI; however, there was little consistency in the tests administered, and the exact deficits and their magnitude varied across studies. The presence, type, and severity of early cognitive deficits should be confirmed with well-designed confirmatory studies; therefore, although consistent, these findings should be considered exploratory. Limited evidence (ie, from a phase I study)21 suggests that LOC is associated with slower cognitive processing speed, and limited evidence (from a phase II study)16
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Table 2
Neuropsychological outcomes
Author (year); Country Experimental studies Suhr and Gunstad (2002)12; U.S. Randomized controlled trial
Suhr and Gunstad (2005)13; U.S. Randomized controlled trial
Population and Follow-Up Information
Inclusion/Exclusion Criteria
Prognostic Factors/Outcomes
Findings
Self-reported MTBI with LOC of 1e30min
Prognostic factors: negative expectations Outcomes: neuropsychological (cognitive) test performance (AVLT, immediate and delayed recall, delayed recognition, CFT, WAIS-III information and block design subtests, WAIS-III digit span and letter number sequencing subtests, COWA total number words, TMT time to complete parts A and B
Diagnosis threat group: performed significantly worse on intellect and memory tests; did not differ from neutral group in basic attention or psychomotor speed; rated themselves as putting less effort into neuropsychological battery; self-rated effort correlated with test performance
Self-reported MTBI with LOC of 1e30min
Prognostic factors: selfreported anxiety (STAI), effort (first 4 subtests of WMT, Likert-type scale), depression (BDI-II) Outcomes: cognitive performance (digit span, letter number sequencing, mental arithmetic, and digit symbol subtests of WAIS-III; TMT; CFT recall trial; free and delayed free recall subtests of WMT; WCST number of categories, number of failures to maintain set, percent perseverative errors
Diagnosis threat group: performed worse than controls on attention/ working memory, psychomotor speed and memory tasks, but not on measures of executive functioning, anxiety, or effort. Effort, anxiety, and depression were not related to cognitive performance
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w2000 undergraduates Inclusion: history of selfcompleted screening reported MTBI with LOC of 1 evaluation; 11% met e30min inclusion criteria; random Exclusion: symptoms of sample was invited to current depression, selfparticipate (72% agreed) reported neurologic history MTBI (nZ36) Diagnosis threat group (participants informed that experiment was being conducted to examine potential negative effects of head injury on cognitive functioning): nZ17; mean age, 18.6y; 35% men; mean education, 13.2y Neutral group: nZ19; mean age, 18.5y; 53% men; mean education, 13.2y w2000 undergraduates Inclusion: history of selfcompleted screening reported MTBI with LOC evaluation; 17% met of 1e30min inclusion criteria; random Exclusion: self-reported sample was invited to history of neurologic participate (81% agreed) disease, current psychiatric Diagnosis threat (participants diagnosis/treatment, informed that experiment learning disability, was being conducted to attention deficit/ examine potential negative hyperactivity effects of head injury on cognitive functioning) group: nZ28; mean age, 18.8y; mean education, 13.3y; 43% men Neutral (control) group: nZ25; mean age, 19.3y; mean education, 13.9y; 40% men
MTBI Case Definition
Author (year); Country Ozen and Fernandes (2011)14; Canada Nonrandomized trial
Population and Follow-Up Information Participants recruited from a group of undergraduate students (nZ5325) who completed an online prescreen questionnaire at the beginning of either the winter, spring, or fall 2009 semester; nZ475 fit MTBI criteria. Diagnosis threat condition (participants informed that experiment was being conducted to examine potential negative effects of head injury on cognitive functioning): MTBI: nZ22; reported past MTBI; mean age, 19.3y; mean education, 13.5y; 41% women Control: nZ21; no history of head injury; mean age, 19.5y; mean education 13.9y; 52% women Neutral condition (participants unaware that effects of MTBI on cognitive functioning were being investigated): MTBI: nZ21; reported past MTBI; mean age, 20.3y; mean education, 13.7y; 57% women Control: nZ23; no history of head injury; mean age, 20y; mean education, 13.8y; 61% women
Inclusion/Exclusion Criteria
MTBI Case Definition
Inclusion: Fit MTBI criteria at least 6mo before testing
Any strike to the head or any Prognostic factors: symptom acceleration/deceleration expectation (diagnosis force that resulted in LOC; threat) LOC 30min; PTA, Outcomes: self-report and disorientation, and/or cognitive performance confusion 400,000) Controls: recruited via volunteer database; no history of head injury with persisting symptoms/
Inclusion: GCS score of 13e15 on first assessment, without falling below 13 at any consecutive assessment at hospital; PTA 30min; F/U: average 4.5d postinjury (2) GCS score 24hr Catchment area of 3 Inclusion: patients with blunt MTBI: blunt head trauma with Prognostic factors: S100B emergency departments in trauma to the head with GCS score of 14 or 15, LOC (pathologic values the northern and central LOC and/or amnesia, GCS 30min, PTA 24h determined as >97.5 parts of Stockholm County, score of 14 or 15, injury percentile in noninjured about 800,000 adult within 24h of being seen at controls) inhabitants, January 2000 emergency department, age Outcome: cognitive to December 2001 15e65y functioning as assessed on (nZ122). Having complete Exclusion: amnesia >24h; LOC tests from the Automated data (nZ97). 35 >30min; those with no Psychological Test (motor noninjured controls clear history of blunt speed, focused and recruited from same trauma, other major selective attention, catchment area. injuries, and major reaction time, and longF/U: 3mo neurologic disorders (those term associative memory); with prior or current information, digit span and psychiatric illness or digit symbols from WAIS-R, alcohol dependence were block span from the WAISnot excluded) R-NI, Buschke Selective Reminding Test, Stroop test, Paced Auditory Serial Addition Test, TMT. PCS as assessed by the RPSQ and self-reported
Findings
Author (year); Country
Population and Follow-Up Information
Inclusion/Exclusion Criteria
MTBI Case Definition
Prognostic Factors/Outcomes cognitive symptoms
Shanmukhi and Panigrahi (2003)20; India
Sundstro¨m et al (2004)23; Sweden
Unknown source population. nZ80 (40 with MTBI, 40 with no injuries) F/U: within 2wk of injury
Inclusion: patients aged 20 e40y, with MTBI, who were working, and whose minimum education qualification was 7th standard. Controls were aged 20e40y, with the same education qualifications, were volunteers who were relatives or friends of the patients, with similar SES. Exclusions for both groups: prior head injury, alcoholism, drug intake, epilepsy, cerebral disease, mental retardation, or significant psychiatric disorder Data from a population-based Inclusion: head injury had to longitudinal study have occurred during the 5y (nZ3500) were used to in between 2 test identify 34 adults who occasions; experienced MTBI during neuropsychological test course of study results must be available APOE 34 negative group: from both pre- and nZ23; mean age, 55.87y; postinjury assessment; mean education, 9.53y; APOE genotype must be 52.2% women available; postinjury score APOE 34 positive group: on Mini-Mental State nZ11; mean age, 58.18y; Examination had to be 23 mean education, 10.05y; Exclusion: severe visual or 45.5% women auditory handicap, Controls: age- and sexmentally retarded or matched; randomly demented persons, native selected from remaining tongue other than Swedish participants
MTBI defined as GCS score of 13e15, LOC 20min, normative CT or surgical findings
Prognostic factor: MTBI vs healthy controls Outcome: serial learning task
American College of Rehabilitation Medicine
Prognostic factors: APOE genotype Outcomes: neuropsychological outcome (9 tests assessing the following domains: recall and recognition tests of episodic memory, fluency tests of semantic memory, visuospatial ability test)
Findings findings are reported elsewhere.) Those with MTBI had disruption of ability to learn and remember serial pattern information in simple and complex patterns within 2wk of injury
Prognosis after mild traumatic brain injury: a review
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Table 2 (continued )
Within-person comparisons showed that APOE 34 positive subjects had a significantly decreased postinjury performance on 3 measures (divided attention, recognition of faces, recall of actions) compared with APOE 34 negative subjects. There was no significant difference in postinjury performance between APOE 34 positive and negative subjects; neither group was impaired relative to controls
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Table 2 (continued ) Author (year); Country Phase I studies Brewer et al (2002)21; U.S.
Tellier et al (2009)22; Canada
Population and Follow-Up Information Convenience sample from university hospital emergency department (nZ40). F/U (100%): 24 and 48h and 1mo (neuropsychological testing conducted at 48h and 1mo)
Trauma center emergency department (nZ125). F/U: 1mo for neuropsychological assessment and 1 and 6mo for subjective complaints
Inclusion/Exclusion Criteria
MTBI Case Definition
Prognostic Factors/Outcomes
Findings
Inclusion: 18e59y, 21 men, 19 women, 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 Inclusion: Patients presenting to emergency department with MTBI
Physiological disruption of brain function followed by disturbance or LOC 1 was sustained factors were prior group. For those with no unexposed for each exposed GHC for 1y prior to TBI during the year. MTBI psychiatric diagnosis and psychiatric history, subject. Use of diagnosis. Patient from 6 diagnosed if ICD-9-CM type of prior psychiatric adjusted RR of any incident administrative data; counties in Puget Sound codes indicated brief (15y, no TBI, selected prescription for psychiatric psychiatric illness given at random and age, sex, and medication or use of MTBI was 1.6 (95% CI, 1.2 enrollment time frequency psychiatric services. e2.0) in first 6mo. Most risk matched. GHC members on Presence and type of occurred during first 6 their assigned reference psychiatric illness recorded e12mo postinjury. MTBI data and continuously in 6-mo blocks after the subjects without prior during the year prior to this reference date. Findings psychiatric illness showed date. No TBI during the year adjusted for medical prolonged pattern of prior to the reference date. comorbidities and comorbid elevated risk of incident injuries. affective disorders from 1e18mo postinjury. MTBI subjects without prior history of psychiatric illness showed increased risk of incident psychotic illness at 13e18mo. No increased risk of either incident affective or psychotic illness for those with history of psychiatric illness Prognostic factors: type of .59% of those with MTBI TBI, age at injury, sex, days committed suicide. SMRs in hospital, codiagnosis of stratified by age and sex substance misuse. showed that the incidence (continued on next page)
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Population of Denmark. Data Inclusion: hospital discharge MTBI: ICD-8 code 850 sources were National between 1979 and 1993 Bureau of Health Registry of with a main or secondary all hospitalization diagnosis of TBI: ICD-8 850
Prognosis after mild traumatic brain injury: a review
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Table 3
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Table 3 (continued ) Author (year); Country
Population and Follow-Up Information
Inclusion/Exclusion Criteria
discharges in Denmark from (MTBI), 800, 801, 803 1979 to 1993 and national (cranial fracture); 851e854 register of deaths. (cerebral lesion). Total: nZ145,440 Exclusion: children aged
REVIEW ARTICLE
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 Linda J. Carroll, PhD,a J. David Cassidy, PhD, DrMedSc,b,c,d,e Carol Cancelliere, DC, MPH,b,c Pierre Coˆte´, DC, PhD,c,e,f Cesar A. Hincapie´, DC, MHSc,b,e Vicki L. Kristman, PhD,e,g,h,i Lena W. Holm, DrMedSc,j Jo¨rgen Borg, MD, PhD,k Catharina Nygren-de Boussard, MD, PhD,k Jan Hartvigsen, PhDd,l From the aSchool of Public Health and Alberta Centre for Injury Control and Research, University of Alberta, Edmonton, Canada; bDivision of Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada; cInstitute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; dInstitute of Sports Science and Clinical Biomechanics, Faculty of Health, University of Southern Denmark, Odense, Denmark; eDivision of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; fFaculty of Health Sciences, University of Ontario Institute of TechnologyCanadian Memorial Chiropractic College Centre for the Study of Disability Prevention and Rehabilitation, Toronto, Ontario, Canada; g Department of Health Sciences, Lakehead University, Thunder Bay, Ontario, Canada; hInstitute of Work and Health, Toronto, Ontario, Canada; i Division of Human Sciences, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada; jDivision of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; kDepartment of Clinical Sciences, Rehabilitation Medicine, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden; and lNordic Institute of Chiropractic and Clinical Biomechanics, Odense, Denmark.
Abstract Objective: To synthesize the best available evidence on objective outcomes after adult mild traumatic brain injury (MTBI). Data Sources: MEDLINE and other databases were searched (2001e2012) for studies related to MTBI. Inclusion criteria included published, peer-reviewed articles in English and other languages. References were also identified from the bibliographies of eligible articles. Study Selection: Randomized controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI cases and assess objective outcomes in adults. Data Extraction: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables. Data Synthesis: Evidence was synthesized qualitatively according to modified SIGN criteria, and studies were categorized as exploratory or confirmatory based on the strength of their design and evidence. After 77,914 records were screened, 299 were found to be relevant and critically reviewed, and 101 were deemed scientifically admissible. Of these, 21 studies that were related to the objective outcomes form the basis of this review. Most evidence indicates the presence of cognitive deficits in the first 2 weeks post-MTBI, and some evidence suggests that
Supported by the Ontario Neurotrauma Foundation (grant no. 2010-ABI-MTBIWHO-871). The funder was not involved in the design or preparation of the study protocol, or in the management of the project, analysis or interpretation of data, or the preparation of the final article. No commercial party having a direct financial interest in the results of the research supporting this article has conferred or will confer a benefit on the authors or on any organization with which the authors are associated. The findings and conclusions in this research are those of the authors alone and do not necessarily represent the official views or policies of the Centers for Disease Control and Prevention or any agency of the United States government. Inclusion of individuals, programs, or organizations in this article does not constitute endorsement by the United States government.
0003-9993/14/$36 - see front matter ª 2014 by the American Congress of Rehabilitation Medicine http://dx.doi.org/10.1016/j.apmr.2013.08.300
Prognosis after mild traumatic brain injury: a review
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complete recovery may take 6 months or a year. A small number of studies indicate that MTBI increases the risk of psychiatric illnesses and suicide. Conclusions: Early cognitive deficits are common, and complete recovery may be prolonged. Conclusions about mortality post-MTBI are limited. This review has implications for expected recovery after MTBI and MTBI-related health sequelae. Well-designed confirmatory studies are needed to understand the medium- to long-term consequences of MTBI and to further evaluate the effect of prior MTBI and injury severity on recovery. Archives of Physical Medicine and Rehabilitation 2014;95(3 Suppl 2):S152-73 ª 2014 by the American Congress of Rehabilitation Medicine
Mild traumatic brain injury (MTBI) or concussion is common in the general population. A previous review on the incidence of MTBI estimated that there are 100 to 300 hospital-treated cases of MTBI per 100,000 persons per year. However, this is likely the tip of the iceberg because there is evidence that much MTBI is not treated at hospitals.1 The main causes of MTBI are falls and motor vehicle collisions, and MTBI is a condition that disproportionately affects the young (teenagers and young adults) and is more common in men than women.1 Given its frequency, having good information on the course of recovery and predictors of recovery is a priority. There have been several systematic reviews examining the presence of cognitive outcomes after MTBI. One of these (published in 2003) reports2 a meta-analysis showing a moderate effect of MTBI on cognitive functioning in the early stages of recovery. Although that review was not designed to track the course of recovery after MTBI (which requires studies with a longitudinal design), the authors extrapolated from mostly cross-sectional studies that, on average, cognitive recovery appears to occur within the first 3 months. A subsequent systematic review3 examined the presence of long-term MTBI-related cognitive impairment (>6mo), and reported that there was insufficient evidence to come to a conclusion. The aim of the current article is to expand and update our knowledge about the presence and course of recovery of MTBIrelated cognitive impairment in adults and prognostic factors for that recovery and to report other objectively measured outcomes of MTBI. A previous systematic review4 (a best evidence synthesis) on the course and prognostic factors for MTBI recovery was published in 2004 by the World Health Organization (WHO) Collaborating Centre Task Force on MTBI. To inform about the course of recovery and prognostic factors for recovery, studies must use a longitudinal design. In the 2004 review,4 only 9 longitudinal studies reporting on cognitive deficits in adults after nonesports-related MTBI were sufficiently methodologically sound to be included in the best evidence synthesis. The limited information available at the time suggested the presence of initial cognitive deficits, but generally good recovery of cognitive functioning. However, the paucity of studies limited the authors’ confidence in this conclusion, leaving questions about how long cognitive recovery typically takes in adults and what preinjury or initial postinjury factors predicted good versus poor cognitive recovery. The review4,5 suggested that much of the research on prognosis in adults was methodologically weak. In particular, the review called for more attention to the control of confounding and to selection of control groups. Specifically, investigators designing research were called on to consider the question of whether factors (eg, pain, medications, psychological distress, and other potential confounders) have an impact on assessment of cognitive functioning of adults with MTBI. Moreover, challenges faced by researchers in interpreting neuropsychological test scores have been
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outlined by Iverson and Gaetz,6 among others. Iverson and Gaetz6 point out that intertest score scatter occurs even in the healthy population, and the more tests are administered, the greater the likelihood that an individual will score in the extreme range, even in the absence of a brain dysfunction. Therefore, cautious interpretation of study findings is warranted. Since the above review was published in 2004, there has been a good deal of research activity in MTBI, and the current update of the WHO Collaborating Centre Task Force was undertaken by an international group of researchers and clinicians, the International Collaboration on MTBI Prognosis (ICoMP). The ICoMP conducted a systematic search, critical review, and best evidence synthesis of the research on MTBI prognosis published since the work of the WHO Collaborating Centre Task Force on MTBI. The current article forms a part of this endeavor and reports on those studies concerned with presence, course of recovery, and predictors of recovery of cognitive outcomes (assessed by neuropsychological measures); psychiatric outcomes of MTBI; mortality outcomes associated with MTBI; and other objectively assessed outcomes in adults subsequent to nonesports-related and nonemilitary-related MTBI.
Methods The protocol registration, case definition, literature search, critical review strategy, and data synthesis are outlined in detail elsewhere7 and in this issue.8 Briefly, the electronic databases MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were systematically searched from 2001 to 2012. Reference lists of all systematic reviews and meta-analyses related to MTBI and all articles meeting the eligibility criteria were checked to ensure that relevant studies were not missed. Articles were screened according to predefined criteria. Inclusion criteria included original, published peer-reviewed research reports in English, French, Swedish, Norwegian, Danish, and Spanish; human participants of all ages; and a minimum of 30 participants with MTBI or concussion. The definition of MTBI had to be consistent (but not necessarily identical) with the definitions provided by the WHO Collaborating Centre Task Force on MTBI5 and the Centers for Disease Control and Prevention.9 Eligible study designs were randomized controlled trials with prognostic information, cohort studies, and case-control studies. Exclusion criteria included cross-sectional studies, case reports, case series, and cadaveric, biomechanical, and laboratory studies. Eligible articles were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria.10 Two reviewers performed independent, in-depth reviews of each eligible study, and a third reviewer was consulted for disagreements. ICoMP members also undertook 3 original
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research projects, one of which is included in this review. These studies were critically appraised by the ICoMP members not involved in their conduct. Data from accepted articles were independently extracted into evidence tables by 2 reviewers, and the evidence was synthesized according to the modified SIGN criteria. A best evidence synthesis was performed to provide conclusions based on the best available evidence. We also synthesized the evidence using the phases of study framework described by Coˆte´ et al11 (table 1). The strongest evidence is found in phase III studies, followed by phase II studies. Phase I studies do not consider confounding and are weaker evidence. Our findings were synthesized separately for cognitive, psychiatric, mortality, and other outcomes in adults with MTBI.
Results Out of 77,914 records screened for our entire review, 2170 fulltext articles were assessed for eligibility, 299 were critically reviewed, and 101 (ie, 34%) were deemed scientifically admissible (fig 1). This article presents the 21 accepted studies (all were published in English) reporting findings on course and prognostic factors associated with neuropsychological findings, psychiatric disorders, suicide subsequent to MTBI, mortality outcomes, and other objective outcomes. These studies form the basis of our best evidence synthesis. The findings are divided into 4 sections: neuropsychological outcomes (table 2), psychiatric outcomes (including suicide) (table 3), other articles reporting on mortality after MTBI (table 4), and other outcomes (table 5).
Neuropsychological outcomes Twelve articles addressed cognitive outcomes of MTBI using cognitive testing (ie, not self-report) (table 2). Two are randomized controlled trials conducted in the U.S.,12,13 1 is a nonrandomized experiment conducted in Canada,14 7 are phase II cohort studies conducted in Israel, New Zealand, Canada, the U.S., Sweden, and India,15-20,23 and 2 are phase I cohort studies conducted in the U.S. and Canada.21,22 Sampling frames were varied: admissions to emergency departments,18,19,21,22 inpatient admissions,15,17 trauma database,16 undergraduate students,12-14 a population-based study,23 and unreported.20 Only 2 studies used repeated testing, which involved tracking cognitive recovery at 48 hours and 1 month in one study,21 and at 2 weeks and 3, 6, and 12 months in the other.19 Comparisons were made with test norms, healthy controls, control group made up of non-TBI injured persons, and preinjury test scores. Finally, 3 studies compared neuropsychological findings under experimentally induced testing conditions, thereby experimentally manipulating the prognostic factor of interest.12-14
List of abbreviations: APOE CT GCS ICoMP LOC MTBI PTA SIGN TBI WHO
apolipoprotein E computed tomography Glasgow Coma Scale International Collaboration on MTBI Prognosis loss of consciousness mild traumatic brain injury posttraumatic amnesia Scottish Intercollegiate Guidelines Network traumatic brain injury World Health Organization
Table 1
Phases of prognostic studies framework
Study Phase Description Phase I
Phase II
Phase III
Hypothesis-generating investigations exploring the associations between potential prognostic factors and health outcomes in a descriptive or univariable way Extensive exploratory analyses focusing on particular sets of prognostic factors, or attempting to discover which factors have the highest prognostic value Large confirmatory studies of explicit prestated hypotheses that allow for a focused examination of the strength, direction, and independence of the proposed relation between a prognostic factor and the outcome of interest
Presence of deficits within the first 2 weeks Five studies16,17,19,20,21 (1 phase I and 4 phase II studies) examined neuropsychological outcomes within the first 2 weeks after injury, with comparisons of test scores of people with MTBI against test normative data, uninjured samples, and individuals with injuries other than TBI. Study findings are as follows. Brewer et al21 studied emergency department admissions for MTBI with loss of consciousness (LOC) of 10 minutes (phase I study). At 48 hours postinjury, there were no deficits in tests of executive functioning, but patients were distractible. Another study17 (phase II) also found MTBI-related distractibility at 4 to 5 days postinjury. That study assessed a sample of patients with and without MTBI, all hospitalized because of their injuries. People with MTBI had Glasgow Coma Scale (GCS) scores of 14 or 15, and were mostly hospitalized because of concurrent injuries, rather than the traumatic brain injury (TBI) itself. In addition to increased distractibility, the Landre et al17 study also found the MTBI group to have deficits in attention and memory compared with the injured non-TBI control group. This design potentially controls for the impact of an injury itself on cognitive functioning, although in this study it is unclear whether the overall injury severity was comparable. Although there are challenges in comparing the severity of different types of injuries, it remains a potential confounder, which suggests caution in interpreting these findings. However, pain intensity and emotional distress were measured in both groups and were unassociated with test scores.17 Similarly, deficits in attention and learning/memory of simple and complex material at 2 weeks post-MTBI were also observed in a third study (phase II). In that study,20 people with MTBI were compared with uninjured age-, education-, and socioeconomic status-matched controls (friends or relatives of the participants). In the first assessment period of a 1-year longitudinal study, Heitger et al19 (phase II study, emergency department sample) also reported verbal learning deficits and speed of information processing deficits in people with MTBI compared with age-, sex-, and education-matched healthy controls from a volunteer database at 1 week postinjury. These findings are not entirely consistent with Brewer,21 who found slowed processing speed only in those with LOC, although there is no information in the Heitger19 study on percentage of participants with LOC. Brewer21 also reported impulsivity and deficits in directed attention only in those with LOC. Heitger19 found no MTBIrelated deficits in sustained or divided attention, information www.archives-pmr.org
Prognosis after mild traumatic brain injury: a review
Fig 1
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Flow diagram of literature search.
processing capacity, short-term and working memory, or general cognitive performance. Finally, Iverson16 compared patients with MTBI with and without computed tomography (CT) abnormalities (phase II study, whose data source was a trauma database). At 4 days postinjury, both groups showed deficits in comparison with test norms, although systematic differences between participants and the normative sample are possible. Patients with CT abnormalities performed more poorly on cognitive tests than those with normative CT; however, effect sizes were small to medium; therefore, the clinical importance of these differences is unclear. Moreover, Iverson16 reports that cognitive test findings did not differentiate those with and without CT abnormalities in a multivariable www.archives-pmr.org
statistical model. Iverson16 concluded that the performance of the 2 groups (those with and without CT abnormalities) was more similar than dissimilar. In summary, there were consistent findings that MTBI is associated with cognitive deficits between 48 hours and 2 weeks post-MTBI; however, there was little consistency in the tests administered, and the exact deficits and their magnitude varied across studies. The presence, type, and severity of early cognitive deficits should be confirmed with well-designed confirmatory studies; therefore, although consistent, these findings should be considered exploratory. Limited evidence (ie, from a phase I study)21 suggests that LOC is associated with slower cognitive processing speed, and limited evidence (from a phase II study)16
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Table 2
Neuropsychological outcomes
Author (year); Country Experimental studies Suhr and Gunstad (2002)12; U.S. Randomized controlled trial
Suhr and Gunstad (2005)13; U.S. Randomized controlled trial
Population and Follow-Up Information
Inclusion/Exclusion Criteria
Prognostic Factors/Outcomes
Findings
Self-reported MTBI with LOC of 1e30min
Prognostic factors: negative expectations Outcomes: neuropsychological (cognitive) test performance (AVLT, immediate and delayed recall, delayed recognition, CFT, WAIS-III information and block design subtests, WAIS-III digit span and letter number sequencing subtests, COWA total number words, TMT time to complete parts A and B
Diagnosis threat group: performed significantly worse on intellect and memory tests; did not differ from neutral group in basic attention or psychomotor speed; rated themselves as putting less effort into neuropsychological battery; self-rated effort correlated with test performance
Self-reported MTBI with LOC of 1e30min
Prognostic factors: selfreported anxiety (STAI), effort (first 4 subtests of WMT, Likert-type scale), depression (BDI-II) Outcomes: cognitive performance (digit span, letter number sequencing, mental arithmetic, and digit symbol subtests of WAIS-III; TMT; CFT recall trial; free and delayed free recall subtests of WMT; WCST number of categories, number of failures to maintain set, percent perseverative errors
Diagnosis threat group: performed worse than controls on attention/ working memory, psychomotor speed and memory tasks, but not on measures of executive functioning, anxiety, or effort. Effort, anxiety, and depression were not related to cognitive performance
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w2000 undergraduates Inclusion: history of selfcompleted screening reported MTBI with LOC of 1 evaluation; 11% met e30min inclusion criteria; random Exclusion: symptoms of sample was invited to current depression, selfparticipate (72% agreed) reported neurologic history MTBI (nZ36) Diagnosis threat group (participants informed that experiment was being conducted to examine potential negative effects of head injury on cognitive functioning): nZ17; mean age, 18.6y; 35% men; mean education, 13.2y Neutral group: nZ19; mean age, 18.5y; 53% men; mean education, 13.2y w2000 undergraduates Inclusion: history of selfcompleted screening reported MTBI with LOC evaluation; 17% met of 1e30min inclusion criteria; random Exclusion: self-reported sample was invited to history of neurologic participate (81% agreed) disease, current psychiatric Diagnosis threat (participants diagnosis/treatment, informed that experiment learning disability, was being conducted to attention deficit/ examine potential negative hyperactivity effects of head injury on cognitive functioning) group: nZ28; mean age, 18.8y; mean education, 13.3y; 43% men Neutral (control) group: nZ25; mean age, 19.3y; mean education, 13.9y; 40% men
MTBI Case Definition
Author (year); Country Ozen and Fernandes (2011)14; Canada Nonrandomized trial
Population and Follow-Up Information Participants recruited from a group of undergraduate students (nZ5325) who completed an online prescreen questionnaire at the beginning of either the winter, spring, or fall 2009 semester; nZ475 fit MTBI criteria. Diagnosis threat condition (participants informed that experiment was being conducted to examine potential negative effects of head injury on cognitive functioning): MTBI: nZ22; reported past MTBI; mean age, 19.3y; mean education, 13.5y; 41% women Control: nZ21; no history of head injury; mean age, 19.5y; mean education 13.9y; 52% women Neutral condition (participants unaware that effects of MTBI on cognitive functioning were being investigated): MTBI: nZ21; reported past MTBI; mean age, 20.3y; mean education, 13.7y; 57% women Control: nZ23; no history of head injury; mean age, 20y; mean education, 13.8y; 61% women
Inclusion/Exclusion Criteria
MTBI Case Definition
Inclusion: Fit MTBI criteria at least 6mo before testing
Any strike to the head or any Prognostic factors: symptom acceleration/deceleration expectation (diagnosis force that resulted in LOC; threat) LOC 30min; PTA, Outcomes: self-report and disorientation, and/or cognitive performance confusion 400,000) Controls: recruited via volunteer database; no history of head injury with persisting symptoms/
Inclusion: GCS score of 13e15 on first assessment, without falling below 13 at any consecutive assessment at hospital; PTA 30min; F/U: average 4.5d postinjury (2) GCS score 24hr Catchment area of 3 Inclusion: patients with blunt MTBI: blunt head trauma with Prognostic factors: S100B emergency departments in trauma to the head with GCS score of 14 or 15, LOC (pathologic values the northern and central LOC and/or amnesia, GCS 30min, PTA 24h determined as >97.5 parts of Stockholm County, score of 14 or 15, injury percentile in noninjured about 800,000 adult within 24h of being seen at controls) inhabitants, January 2000 emergency department, age Outcome: cognitive to December 2001 15e65y functioning as assessed on (nZ122). Having complete Exclusion: amnesia >24h; LOC tests from the Automated data (nZ97). 35 >30min; those with no Psychological Test (motor noninjured controls clear history of blunt speed, focused and recruited from same trauma, other major selective attention, catchment area. injuries, and major reaction time, and longF/U: 3mo neurologic disorders (those term associative memory); with prior or current information, digit span and psychiatric illness or digit symbols from WAIS-R, alcohol dependence were block span from the WAISnot excluded) R-NI, Buschke Selective Reminding Test, Stroop test, Paced Auditory Serial Addition Test, TMT. PCS as assessed by the RPSQ and self-reported
Findings
Author (year); Country
Population and Follow-Up Information
Inclusion/Exclusion Criteria
MTBI Case Definition
Prognostic Factors/Outcomes cognitive symptoms
Shanmukhi and Panigrahi (2003)20; India
Sundstro¨m et al (2004)23; Sweden
Unknown source population. nZ80 (40 with MTBI, 40 with no injuries) F/U: within 2wk of injury
Inclusion: patients aged 20 e40y, with MTBI, who were working, and whose minimum education qualification was 7th standard. Controls were aged 20e40y, with the same education qualifications, were volunteers who were relatives or friends of the patients, with similar SES. Exclusions for both groups: prior head injury, alcoholism, drug intake, epilepsy, cerebral disease, mental retardation, or significant psychiatric disorder Data from a population-based Inclusion: head injury had to longitudinal study have occurred during the 5y (nZ3500) were used to in between 2 test identify 34 adults who occasions; experienced MTBI during neuropsychological test course of study results must be available APOE 34 negative group: from both pre- and nZ23; mean age, 55.87y; postinjury assessment; mean education, 9.53y; APOE genotype must be 52.2% women available; postinjury score APOE 34 positive group: on Mini-Mental State nZ11; mean age, 58.18y; Examination had to be 23 mean education, 10.05y; Exclusion: severe visual or 45.5% women auditory handicap, Controls: age- and sexmentally retarded or matched; randomly demented persons, native selected from remaining tongue other than Swedish participants
MTBI defined as GCS score of 13e15, LOC 20min, normative CT or surgical findings
Prognostic factor: MTBI vs healthy controls Outcome: serial learning task
American College of Rehabilitation Medicine
Prognostic factors: APOE genotype Outcomes: neuropsychological outcome (9 tests assessing the following domains: recall and recognition tests of episodic memory, fluency tests of semantic memory, visuospatial ability test)
Findings findings are reported elsewhere.) Those with MTBI had disruption of ability to learn and remember serial pattern information in simple and complex patterns within 2wk of injury
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Table 2 (continued )
Within-person comparisons showed that APOE 34 positive subjects had a significantly decreased postinjury performance on 3 measures (divided attention, recognition of faces, recall of actions) compared with APOE 34 negative subjects. There was no significant difference in postinjury performance between APOE 34 positive and negative subjects; neither group was impaired relative to controls
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Table 2 (continued ) Author (year); Country Phase I studies Brewer et al (2002)21; U.S.
Tellier et al (2009)22; Canada
Population and Follow-Up Information Convenience sample from university hospital emergency department (nZ40). F/U (100%): 24 and 48h and 1mo (neuropsychological testing conducted at 48h and 1mo)
Trauma center emergency department (nZ125). F/U: 1mo for neuropsychological assessment and 1 and 6mo for subjective complaints
Inclusion/Exclusion Criteria
MTBI Case Definition
Prognostic Factors/Outcomes
Findings
Inclusion: 18e59y, 21 men, 19 women, 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 Inclusion: Patients presenting to emergency department with MTBI
Physiological disruption of brain function followed by disturbance or LOC 1 was sustained factors were prior group. For those with no unexposed for each exposed GHC for 1y prior to TBI during the year. MTBI psychiatric diagnosis and psychiatric history, subject. Use of diagnosis. Patient from 6 diagnosed if ICD-9-CM type of prior psychiatric adjusted RR of any incident administrative data; counties in Puget Sound codes indicated brief (15y, no TBI, selected prescription for psychiatric psychiatric illness given at random and age, sex, and medication or use of MTBI was 1.6 (95% CI, 1.2 enrollment time frequency psychiatric services. e2.0) in first 6mo. Most risk matched. GHC members on Presence and type of occurred during first 6 their assigned reference psychiatric illness recorded e12mo postinjury. MTBI data and continuously in 6-mo blocks after the subjects without prior during the year prior to this reference date. Findings psychiatric illness showed date. No TBI during the year adjusted for medical prolonged pattern of prior to the reference date. comorbidities and comorbid elevated risk of incident injuries. affective disorders from 1e18mo postinjury. MTBI subjects without prior history of psychiatric illness showed increased risk of incident psychotic illness at 13e18mo. No increased risk of either incident affective or psychotic illness for those with history of psychiatric illness Prognostic factors: type of .59% of those with MTBI TBI, age at injury, sex, days committed suicide. SMRs in hospital, codiagnosis of stratified by age and sex substance misuse. showed that the incidence (continued on next page)
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Population of Denmark. Data Inclusion: hospital discharge MTBI: ICD-8 code 850 sources were National between 1979 and 1993 Bureau of Health Registry of with a main or secondary all hospitalization diagnosis of TBI: ICD-8 850
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Table 3
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Table 3 (continued ) Author (year); Country
Population and Follow-Up Information
Inclusion/Exclusion Criteria
discharges in Denmark from (MTBI), 800, 801, 803 1979 to 1993 and national (cranial fracture); 851e854 register of deaths. (cerebral lesion). Total: nZ145,440 Exclusion: children aged
