Therapy and rehabilitation of mild brain injury/concussion: Systematic review

Abstract

Background:

Assessment of therapies for the key consequences of mild traumatic brain injury (mTBI)/concussion is required.

Objective:

Identify all RCTs of mTBI/concussion therapy, risks of bias, and therapies with significant positive results.

Methods:

17 electronic, 9 grey-literature databases searched without language/date restrictions; independent assessment of 1450 Abstracts/titles, 141 fulltext articles, 14 included RCTs.

Results:

Four RCTs used American Congress of Rehabilitation TBI definition, others used unique definitions. Risk of bias: 43% low risk randomization; 14% concealed assignments; 21% blinded participants/personnel; 57% blinded assessors; 64% low risk attrition; 100% no selective reporting. Eleven RCTs included only mTBI. Ten significant positive results: six cognitive behavioral therapy (CBT), three videotape, pagers or personal digital assistants, and one physical therapy. One of referrals to health professionals no significant positive results. Three RCTs included both mTBI and moderate TBI. We wished to assess if authors proved using same interventions with both groups is appropriate. Two used CBT, one used pagers. All three RCTs significant positive results but results for their mild and moderate TBI patients were not separated. Two RCTs assessed return to work and no differences between intervention.

Conclusion:

Of 14 RCTs, six CBT, four digital assistants or videotape feedback and one physical therapy all had significant positive results. One referred patients to consultants and no significant positive results. Two assessed return to employment and no differences between interventions. Limitations are: (1) only four RCTs used the same concussion definition; (2) average age 38 (except for one study of adolescents, (3) all studies used unique interventions; (4) most authors used multiple interventions and effects could not be separated; (5) substantial attrition from eligibles to randomization, (4) only 64% at low risk from randomization, (5) 80 different outcome measures and meta-analysis was not possible, (6) only two studies assessed return to work.

Keywords

Concussion mild traumatic brain injury evaluation therapy systematic review

1 Introduction

The definitions of mild traumatic brain injury (mTBI) and concussion are used almost interchangeably (Table 1). The wide variety of interventions assessed in systematic reviews to date illustrates the large number of potential consequences from mTBI/concussion, the problems of identifying for each patient or groups of patients the key specific consequences of their injury, providing therapies that significantly improve those dysfunctions, and disentangling the individual effects of multiple therapies in studies which employ multiple interventions.

Table 1
Definitions of mild traumatic brain injury (mTBI) and concussion

Mild mTBI Diagnostic criteria of the American Congress of Rehabilitation Medicine ( ACRM) Special Interest Group on Mild Traumatic Brain Injury: “A traumatically induced physiological disruption of brain function, as manifested by at least one of the following: any loss of consciousness, any loss of memory for events immediately before or after the accident, any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused) and focal neurologic deficit(s) that may or may not be transient, but where the severity of the injury does not exceed the following: loss of consciousness of approximately 30 min or less, after 30 min an initial Glasgow Coma Scale score of 13–15, and post-traumatic amnesia not greater than 24 hr.” (Ruff et al., 2009).

mTBI definition of the WHO task force*: “MTBI is an acute brain injury resulting from mechanical energy to the head from external physical forces. Operational criteria for clinical identification include: (i) 1 or more of the following: confusion or disorientation, loss of consciousness for 30 minutes or less, post-traumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; (ii) Glasgow Coma Scale score of 13–15 after 30 minutes post-injury or later upon presentation for healthcare. These manifestations of MTBI must not be due to drugs, alcohol, medications, caused by other injuries or treatment for other injuries (e.g. systemic injuries, facial injuries or intubation), caused by other problems (e.g. psychological trauma, language barrier or coexisting medical conditions) or caused by penetrating craniocerebral injury.” (Ruff et al., 2009).

Definition of Concussion of the Concussion in Sport Group: “A concussion is a disturbance in brain function caused by a direct or indirect force to the head. It results in a variety of non specific signs and/or symptoms and most often does not involve loss of consciousness. Concussion should be suspected in the presence of any one or more of the following: Symptoms (e.g., headache), or Physical signs (e.g., (e.g., unsteadiness), or Impaired brain function (e.g., confusion) or Abnormal behaviour (e.g., change in personality).” [Concussion in Sport Group, SCAT3 and SCAT 5].

Mild mTBI Diagnostic criteria of the American Congress of Rehabilitation Medicine ( ACRM) Special Interest Group on Mild Traumatic Brain Injury: “A traumatically induced physiological disruption of brain function, as manifested by at least one of the following: any loss of consciousness, any loss of memory for events immediately before or after the accident, any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused) and focal neurologic deficit(s) that may or may not be transient, but where the severity of the injury does not exceed the following: loss of consciousness of approximately 30 min or less, after 30 min an initial Glasgow Coma Scale score of 13–15, and post-traumatic amnesia not greater than 24 hr.” (Ruff et al., 2009).
mTBI definition of the WHO task force*: “MTBI is an acute brain injury resulting from mechanical energy to the head from external physical forces. Operational criteria for clinical identification include: (i) 1 or more of the following: confusion or disorientation, loss of consciousness for 30 minutes or less, post-traumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; (ii) Glasgow Coma Scale score of 13–15 after 30 minutes post-injury or later upon presentation for healthcare. These manifestations of MTBI must not be due to drugs, alcohol, medications, caused by other injuries or treatment for other injuries (e.g. systemic injuries, facial injuries or intubation), caused by other problems (e.g. psychological trauma, language barrier or coexisting medical conditions) or caused by penetrating craniocerebral injury.” (Ruff et al., 2009).
Definition of Concussion of the Concussion in Sport Group: “A concussion is a disturbance in brain function caused by a direct or indirect force to the head. It results in a variety of non specific signs and/or symptoms and most often does not involve loss of consciousness. Concussion should be suspected in the presence of any one or more of the following: Symptoms (e.g., headache), or Physical signs (e.g., (e.g., unsteadiness), or Impaired brain function (e.g., confusion) or Abnormal behaviour (e.g., change in personality).” [Concussion in Sport Group, SCAT3 and SCAT 5].

^*The ACRM and WHO definitions can be used almost interchangeably because they focus on the same four diagnostic criteria, but differ on the use of “transient” and “dazed.”

The wide-ranging potential effects of mTBI/concussion are also reflected in the varied focus of systematic reviews and studies on different consequences of mTBI/concussion. The INCOG group identified five possible key consequences: posttraumatic amnesia and delirium (Ponsford et al., 2014a), decreased attention and information processing (Ponsford et al., 2014b); decreased executive function and self-awareness (Tate et al., 2014), decreased cognitive communication (Togher et al., 2014), and decreased memory (Velikonja et al., 2014).

Another focus of therapy is the manifestations of central nervous system or vestibular dysfunction (vertigo, dizziness and imbalance) (Gurley, Hujsak & Kelly, 2013), postural stability (Ruhe, Fejer, Gãnsslen, & Klein, 2014), neck pain and headache (Schneider et al., 2014), problems with ocular function (abnormalities of saccades, pursuit eye movements, convergence, accommodation and vestibular-ocular reflex) (Ventura, Jancuska, Balcer, & Galetta, 2015), often resulting in multidisciplinary rehabilitation from physiotherapists, occupational therapists, speech pathologists and specialized vestibular therapists.

Studies have also focused on issues of return to play and return to work, the relative roles of therapy and rest, the balance between physical and cognitive rehabilitation, and the role of medication (Burke, Fralick, Nejatbakhsh, Tartaglia, & Tator, 2014). Fatigue, sleep disturbances, increased visual and auditory sensitivity and anxiety are also frequent (Bayley et al., 2014).

To assess the individual effects of mTBI/concussion on patients or groups of patients presenting for therapy, to design interventions and assess if they provide significant improvement in symptoms for each patient are thus complex tasks.

1.1 Systematic reviews

Twenty-two systematic reviews of concussion/traumatic brain injury were identified and those with a literature search within the last five years were retained for assessment of identified studies and their results. The International Cognitive rehabilitation guidelines (INCOG) review group (searches to 1 May 2012) published one methods overview (Bayley et al., 2014) and five guidelines (Ponsford et al., 2014b; Velikonja et al., 2014; Tate et al., 2014; Togher et al., 2014; Ponsford et al., 2014a). They defined Level A evidence as at least one meta-analysis, systematic review or RCT of appropriate size with a relevant control group, Level B as cohort studies or small sample RCTs, and Level C as expert opinion. For posttraumatic amnesia/delirium they identified no RCTs, for attention and information processing speed they identified 8 RCTs and assigned an A recommendation for methylphenidate (7 RCTs) and against mindfulness meditation (1 RCT); for executive function and self-awareness they identified 16 RCTs and assigned an A recommendation for metacognitive strategies (8 RCTs), strategies to improve the capacity to analyze and synthesize information (8 RCTs) and direct corrective feedback (3 RCTs); for cognitive communication they identified 10 RCTs and assigned A recommendations for rehearsing communication skills (4 RCTs), education of communication partners (3 RCTs), and patient-identified goals for social communication (7 RCTs); and for memory 10 RCTs and assigned an A recommendation for metacognitive strategies (3 RCTs), and environmental supports and reminders (5 RCTs).

However, the key problems of these five systematic reviews are that they do not assess the risk of bias of any RCT (or the systematic reviews they cite), do not provide any quantitative results for any outcome measure or undertake any meta-analyses, and do not identify whether studies include mild, moderate or severe TBI patients or whether results are reported separately within studies for each of these groups (which can only be ascertained by reading each article on their reference lists).

A systematic review of electronic portable devices (search to end of 2012) identified no RCTs (Charters, Gillett, & Simpson, 2015). The Cochrane review of cognitive rehabilitation for executive dysfunction (Chung, Pollock, Campbell, Durward, & Hagen, 2013). included 18 RCTs (11 stroke and 7 TBI). Of the RCTs of TBI four included mild to severe TBI without separating the outcomes and one included stroke patients and thus only the two RCTs of mild TBI are included in the current review. A systematic review of cognitive prosthetic technology for people with memory impairments (Jamieson, Cullen, McGee-Lennon, Brewster, & Evans, 2014), (search to 7 December 2012) identified 32 single case and 11 “group studies” but did not state if they were RCTs; on reviewing the studies two are RCTs and are included in the present review. A systematic review of occupation-based cognitive rehabilitation for TBI (Park, Maitra, & Martinez, 2015), (search to July 2014) identified eight RCTs (six included severe TBI and one included both TBI and stroke patients without separating the outcomes for mTBI and are excluded from the present review. A systematic review of virtual reality games for TBI (Pietrzak, Pullman, & McGuire, 2014), (search to 19 July 2013) identified five pilot RCTs and concluded that evidence of effect is “very limited.”). A systematic review that examined the characteristics of current trials of concussion (Burke et al., 2015), (search to 3 October 2013) identified 71 trials (64 RCTs) and noted that 44% did not define concussion/TBI and 37% included mild with moderate and 18% moderate and severe TBI. The review did not assess risk of bias or provide any quantitative results or meta-analysis. A systematic review of cognitive rehabilitation (van Heugten, Gregorio, & Wade, 2012), (search to August 2010) identified 95 RCTs but did not separately report outcomes for stroke, TBI and other patients, and merely reported “In more than half of the studies, the experimental treatment was more effective than the control treatment... ” A systematic review for the US Department of Health and Human Services of multidisciplinary rehabilitation programs was limited to moderate and severe TBI, did not separate outcomes for moderate to severe TBI, and did not comment on whether any of the interventions could be used for mTBI (Brasure et al., 2013).

Thus an up-to-date systematic review of interventions for individuals with concussion/mTBI is needed in all languages and which evaluates their risks of bias (randomisation, concealment of group assignment from the researchers, blinding of patients and therapists, blinding of outcome assessors, attrition of patients and attrition of data elements for individual patients, and selective reporting) and assesses which interventions have been proven to show statistically significant improvements in the key consequences of mTBI/concussion.

1.2 Purpose of the present review

To identify all RCTs of therapy for concussion/mTBI, assess their risks of bias, identify interventions which have significant positive, negative or neutral outcomes, and identify gaps in the literature for which further research is needed.

2 Methods

2.1 Data sources and eligibility criteria

A comprehensive search was conducted in the following databases using pre-determined search strategies discussed between the librarian, principal investigator and co-investigators: MEDLINE, EMBASE, EBM Reviews (Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic Evaluation Database), PubMed, PubMed Central, Web of Science, CINAHL, SPORTDiscus, Family & Society Studies Worldwide, Family Studies Abstracts, and Health Source-Nursing/Academic Edition. In addition, nine grey literature resources were searched, including Google, Google Scholar, OpenDOAR (www.opendoar.org), Health Sciences Online [HSO] (www.hso.info), ProQuest Dissertations & Theses, OAISter (http://oaister.worldcat.org), Sports Concussion Institute (http://concussiontreatment.com), Brain Trauma Foundation (https://www.braintrauma.org), and the Canadian Concussion Collaborative (http://casem-acmse.org/education/ccc) to May 2017. No limits on publication date were applied, and the search included studies in all languages and from all countries. All included RCTs and reviews were individually entered in the PubMed single citation matcher and all relevant citation chains followed up to identify relevant references. The complete revised search strategy is listed in Fig. 1.

Fig.1

Search Strategy.

Because multi-disciplinary rehabilitation is often employed, individual searches were also undertaken in MEDLINE for randomised controlled trials and systematic reviews of physiotherapy, occupational therapy, speech-language pathology and vestibular therapy for mTBI/concussion.

2.2 Inclusion/exclusion criteria

RCTs or C-RCTs (cluster-randomised controlled trials) were included which assessed the outcomes of therapy for individuals with concussion/mTBI. RCTs which also included individuals with severe TBI were excluded if the outcomes for the mTBI individuals could not be separately identified, because patients with severe TBI require different therapies. Studies with mixed populations (e.g. stroke, brain tumor or abscess or mTBI/concussion) in which the outcomes for the concussed/mTBI patients could not be separated were excluded. A subset of RCTs was included if the authors used the same intervention for mild and moderate TBI, to assess if the same intervention could efficiently be used for both groups.

2.3 Data extraction and analysis

All abstracts/titles were read independently, and articles elected for full-text assessment and data were entered in tables independently by two reviewers. We included only RCTs and excluded all studies with n < 20 (because the lower sample size limit for statistical tests such as Chi² is 20).

2.4 Risk of bias assessment

The Cochrane risk of bias tool for RCTs was used (Higgins & Green, 2011).

3 Results

3.1 Literature search

1,450 potential articles were identified following a search of the databases. After removal of duplicates, the titles and abstracts of 1,028 papers were screened for relevance, yielding 141 articles for full-text review and 14 were selected as relevant to the goals of this review. (Fig. 2. PRISMA Flow Chart; Tables 2 and 3). Of these 12 were RCTs and 2 were C-RCTs (Rath, Simon, Langenbahn, Sherr, & Diller, 2003; Vas et al., 2015). Eleven RCTs were therapy for patients with mTBI/concussion. To assess whether the same therapy could be provided to patients with mild or moderate TBI/concussion we included a subset of three such RCTs (Table 3) but found that the authors did not separately report the results for mTBI and moderate TBI individuals and did not evaluate whether the same therapy could be appropriately used with both groups. For institutions with limited therapeutic resources who might wish to treat these patients together, the literature does not provide an answer to this question.

Fig.2

Prisma Flow Diagram.

Table 2

RCTs of interventions for mild traumatic brain injury/concussion

Author, date, country, purpose	Study design; power computation; time from TBI to starting therapy; follow-up; definition of TBI;	Population	Intervention	Comparison	Outcome measures	Results
Cognitive therapy interventions
Ashman 2014, USA]; purpose: compare CBT and psychotherapy to improve depression after TBI	RCT; power computation: none; time from TBI to starting therapy: not stated; follow-up: 3 months; intention-to-treat; definition of TBI: “Having a TBI as a result of a blow to the head followed by a loss of consciousness or period of being dazed of confused or a period of posttraumatic amnesia or clinical signs of altered neurological function;”	Community participants recruited at Mount Sinai Medical Center, NY; depressed, on stable antidepressant dosage×6 months; 108 assessed, 28 excluded (not depressed or substance abuse or psychiatric diagnosis); 80 eligibles, 77 randomised, 42 completed; CBT n = 28 (22 completed treatment), SPT n = 26 (21 completed treatment); average age: 47.5 years; gender: 32f, 42m	16 sessions×50 minutes individual CBT to improve memory, processing speed, executive dysfunction using cognitive restructuring, creation of less self-critical dialogues, mastery, planning, social outreach, relaxation, error-correcting feedback	16 sessions individual psychotherapy to improve ability to cope with daily living problems (reduce symptoms, improve self-esteem, naming problems, praise, reassurance, normalizing, encouragement, anticipatory guidance, clarification, confrontation)	Main outcome, measures: DSM-IV Structured Clinical Interview; BDI-II; STAI; Life3-QOL; LES; ISEL	At 3 months all participants improved on BDI-II (p = 0.003), STAI (p = 0.03), Life-3 QOL (<0.001) and LES negative (p = 0.02); at 3 months 35% of intervention group no longer met depression definition, 17% of control group (ns)
Bédard 2013 Canada; purpose compare CBT for depression after TBI to no intervention	RCT; power computation: to detect 5-point difference in change scores between groups: BDI-II Overall, 0.80; BDI-II Cognitive-Affective: 0.99; BDI-II Somatic: 0.99; estimated dropout ≤ 30%, needed 18-21 individuals/arm; time from TBI to starting therapy: not stated; follow-up; 3 months; definition of TBI: “damage to living brain tissue caused by an external, mechanical force. TBI is usually characterized by a period of altered consciousness (amnesia or coma) that can be very brief (minutes) or very long (months/indefinitely;”	TBI patients with depression (BDI-II score ≥ 16), outpatient programs, advertisements, referrals from health practitioners; 119 eligibles; 100 randomised and 5 assigned to the intervention group; 76 completed (38 intervention, 38 control); not intention-to-treat analysis; average age: 47 years; gender; 19f, 24 m	Mindfulness based cognitive therapy (meditation, breathing exercises, yoga, awareness of thoughts and feelings, acceptance, staying in the present, daily home meditation, with focus concussion problems of attention concentration and memory)	Wait list control	Main outcome, measure: BDI-II; Secondary outcome measures: PHQ-9, SCL-90R	Intervention group improved on BDI-II overall p < 0.001; BDI cognitive p < 0.001; BDI somatic p < 0.001; PHQ9 overall p < 0.001; SCL-90 R depression subscale p < 0.001
McMillan et al., 2002, UK; purpose: to assess the efficacy of brief mindfulness training for attention problems	C-RCT (3 arms); power computation: none; time from TBI to starting therapy: average 1 year; follow-up: 6 and 12 months; Definition of TBI: “problems of attention on neuropsychological testing, or who reported attentional problems in everyday life ... no previous head injuries or major neurological disease ... between three months and one year post-injury and living at home, no significant language problems, fully oriented in time, place, and person ... aware of cognitive problems, including concentration difficulties;”	Eligibles: TBI patients who showed problems of attention on neuropsychological testing, or who reported attentional problems in everyday life; patients had between three months and one year post-injury and living at home; Randomised: 145; Completed: treatment phase 0.130 (ACT (n = 44) PE (n = 38) Control (n = 48); average age: ACT 34.6 (11.4), PE 31.4 (13.0), Control 36.2 (13.4); gender: ACT 35m:9f, PE 30m:8f, Control 36m:12f	Attentional control training (ACT) (breathing-based training); five 45 min sessions supervised practice over 4 weeks using ACT audiotape. Daily practice in the intervening periods.	Physical exercise Identical amount of therapist contact. Control group No therapist contact.	Main Outcome Measures: TEA, AMIPB, IPB, PASAT, TMT, SMQ, CFQ, HADQ, GHQ, PCSQS	Significant differences (p < 0.05) on CFQ, TEA Map Search, TEA El. Counting Distraction, TEA Visual Elevator accuracy; TEA Telephone Search, TEA Telephone search dual task, TEA Lottery; all other outcome measures n.s.
Rath et al., 2003 USA; purpose: to assess the efficacy of group treatment of problem-solving deficits	C-RCT (5 successive cohorts randomly assigned to innovative (experimental) or conventional (control) treatments; power computation: none; time from TBI to starting therapy: >1 year; Follow-up: 6 months; definition of TBI: “participants were required to meet minimum ”basic skill “ criteria ... the ability to sustain attention for an hour-long session, take organised notes, give and receive feedback, state cognitive strengths and weaknesses, and relate to others with adequate social skills;”	Eligibles: not stated; 60 outpatients with TBI from large outpatient neuropsychological rehabilitation programme at major metropolitan medical cente; randomised: Innovative 32, Conventional group 28; completed: innovative 27, conventional 19); Age range: 22 to 65 years; average age = 43.6 years; gender: 37f, 23 m;	Innovative treatment: 24 sessions (12 sessions emotional self-regulation/problem-orienting skills; 12 problem-solving skills). Structured agenda included announcements, review of previous sessions, session’s goal and exercise. Group format (5 to 8 participants); 2 h session/week; weekly 1 h “consolidation sessions” (groups of 1–3 participants)	Conventional: 24 sessions (cognitive remediation and psychosocial components). Structured agenda included announcements, review of previous sessions, session’s goal and exercise. Group format (5 to 8 members), 2 to 3 h session/week.	WVCT; SCWT; FAS-COWAT; Will-Temperament Scale; WMS-III; Watson-Glaser Critical Thinking Appraisal; WAIS-III; SIP; CIQ; PCL; BSI; RSES; WCST; PSI; PSQ; PSRPT	Innovative Group Visual Memory immediate recall (p < 0.001); Logical memory immediate recall (p = 0.001); Logical memory delayed recall (p = 0.01); Visual Memory delayed recall (p = 0.01); RSES improved esteem (p < 0.05); WCST fewer perseverative responses p < 0.05); PSI problem solving (p = 0.005); PSQ Clear Thinking and Self-Regulation p < 0.01); PSRPT interpersonal problem solving (p < 0.005); Conventional Group: Watson Glaser Critical Thinking Test (p < 0.05); PCL fewer somatic symptoms (p < 0.005); PCL observer rated less severe cognitive and somatic symptoms (p < 0.05); PSQ emotional self-regulation (p < 0.01)
Silverberg 2013, Canada; purpose: CBT to prevent chronic post-concussion syndrome compared to written information	RCT; power computation: none; time from TBI to starting therapy: ≤ 6 weeks; follow-up; 3 months; definition of TBI: “American Congress of Rehabilitation criteria for MTBI and subjectively reported at least 1 symptom attributable to head trauma;”	Eligibles 884 (32 declined, 271 low risk for poor outcome, 265 head trauma >6 weeks ago, 124 positive neuroimaging, 116 prior MTBI); randomised: ”28 consecutive referrals to concussion clinic within 6 weeks of injury; completed 20; Intervention n = 13 (11 at 3 months), control n = 11 (9 at 3 months); not intention-to-treat analysis; average age: 38.5 years; gender: 15f, 11 m	(1) Education, reassurance, symptom management by occupational therapist (3 hours); (2) CBT to alter maladaptive beliefs and coping behaviours, increase perceived control	(1) Education, reassurance, symptom management by occupational therapist (3 hours)	Main outcome, measure: RPQ; Secondary outcome measures: HADS, ICD-10, lPQ-R, M2PI,	At 3 months: ICD-10 PCS definition of chronic post concussion syndrome: Intervention 7/13, Control 10/11 (p = 0.047); RPQ: Intervention 17.9, Control 28.7 (ns); IPQ-R Consequences, Personal Control, Emotion (all significant at p≤0.025; Identity, Timeline, Coherence (all n.s.); HADS (n.s)
Vas 2015, USA; purpose: Strategic Memory Advanced Reasoning Training for TBI persistent mild functional deficits, compared to an active learning programme	C-RCT; power computation: none; time from TBI to starting therapy: >6 months; “Over two-thirds of the participants sustained their injuries nearly 10 years ago, so there was limited access to medical records that might provide reports of the severity of the TBI;“ follow-up: 3 months; definition of TBI: “individuals with a GOS-E score of 6–7 (characterising mild levels of functional impairments supporting the classification of mild-spectrum TBI”; “all participants reported difficulty in returning to pre-TBI levels of work ability and/or obtaining gainful employment as a result of cognitive difficulties in their initial interview”	Eligibles: not stated; Randomised: “60 community dwelling individuals with a history of TBI in chronic stages of recovery (>6 months post-injury)”; 47 were civilians and 13 were veterans”; completed: 60; Intervention n = 31 (1 missed cognitive testing), control n = 29 (1 missed cognitive testing); not intention-to-treat analysis; age range: 19 to 65 years; gender: 28f, 32m	Strategic Memory and Reasoning Training (SMART) program: set of 3 multidimensional and inter-related strategies to apply to wide range of everyday tasks. Strategies draw upon top-down processes to improve cognitive control functions, including strategic attention, integrative reasoning and innovation. Group format: 4 to 5 participants. Total 18 hours training (12 group sessions×1.5 hours), over 8 weeks.	Brain Health Workshop (BHW) is an information-based manualized program covering education topics relevant to participants’ health and brain injury (e.g., brain anatomy, brain functioning, general brain health, effects of lifestyles on brain health such as different diets and exercises, and cognitive changes following a TBI). Group format: 4 to 5 participants. Total 18 hours training (12 group sessions×1.5 hours)	Main Outcome Measures: TOSL gist reasoning and memory for text details; Wechsler digit backward; Daneman Listening span; D-KEFS Color-Word Inhibition task-3; D-KEFS Hayling sentence completion; D-KEFS Trail making-4; D-KEFS Category switching; WMS Logical Memory; FSE; CIQ; Sherer AQ; BDI-II; PTSD checklist; MRI imaging of resting state cerebral blood flow.	SMART compared to BHW: Gist reasoningp = 0.02; D-KEFS trail making timep = 0.03; D-KEFS trail making errorsp < 0.001; D-KEFS memory for detailsp = 0.01; D-KEFS Contrastp = 0.01; WMS delayed recallp = 0.002; WMS Awarenessp = 0.02; Post-traumatic stress disorder Check List:p = 0.004; Beck Depression Inventoryp = 0.003; MRI cerebral blood flow p < 0.05
Individualized referral to health professionals
Andersson 2007, Sweden; purpose: assessment by rehabilitation specialist and referral to other health professionals vs.usual access to services	RCT; power computation: 384 patients to detect 15% reduction in concussion symptoms; time from TBI to starting therapy: 2–8 weeks; follow-up; 1 year; definition of TBI: American Congress of Rehabilitation criteria for MTBI	Recruited at Södra Älsborgs hospital Sweden; 1997–2000; eligibles: “of 1791 consecutive patients with MTBI, 395 individuals,16–60 years of age, met the MTBI definition” (996 excluded as <16 or >60, 151 outside study area, 92 substance abuse, 33 previous mTBI); 314 randomised to intervention (and rehabilitation specialist examined 96); 131 control; intention-to-treat analysis; average age: 33 years; gender: 150f, 245m	Information, counselling, assessment of need of medication for pain, sleep disturbance; coping strategies; diary for patients with memory problems; 78 referred to occupational therapist, unstated numbers to physiotherapist, social worker or medical specialists as indicated;	No statement other than: “All patients continued to have access to existing hospital services, although local clinical services normally do not include follow-up of patients after an uncomplicated head injury”	Main outcome, measures: PCSQ, LiSat-11; Secondary outcome measures: CIQ, SF-36; Interest Checklist; Role Checklist (Oakley); Job Satisfaction Checklist (Simovici)	No differences on any outcome measure
Videotape, pager or personal digital assistant
Dowds 2011, USA; purpose: “To determine whether automated reminders from 2 contemporary personal digital assistant (PDA) devices produce higher rates of timely task completion in people with traumatic brain injury”	RCT; 8-week memory aid usage study, multiple cross-over design; power computation: none; time from TBI to starting therapy: not stated; follow-up: not stated; definition of TBI: “documented history of TBI; self-perceived memory impairment ... meeting screening criteria for hearing, motor functioning and cognitive functioning adequate for device usage;”	Eligibles: TBI subjects participating in outpatient programs, group homes, and other long-term care settings; randomised: 36; Completed: 36 adults aged 18 to 66 years with TBI and self-determined complaints of memory impairment; average age: 42.1 years. gender: 19f, 17m	3 conditions: (1) paper as a memory aid; (2, 3) two 2 conditions using different palmtop computers. Memory aid condition changed each week for each participant in a randomly determined order.	usual approach to remembering without introduction of a memory aid;	Main Outcome Measure: Rate of timely completion of assigned call-in tasks and personalized tasks.	Timely Task Completion: Baseline condition 27%; paper planner condition 26% : Microsoft Pocket PDA 38%; Palm OS PDA 56%; Microsoft PDA vs. baseline (p < 0.001): Palm PDA vs. baseline (p < 0.005); Palm vs Microsoft PDA (p 0.0005)
Schmidt et al., 2013, Australia; purpose: to compare the effect of different methods of feedback on impaired self-awareness after TBI	RCT; Power computation: “sample of 54 participants (18/group) would provide 80% probability of detecting 30% reduction in errors, assuming 10% loss to follow-up and α= 005; “ time from TBI to starting therapy: mean = 4 years; follow-up: not stated; definition of TBI: “sustained a TBI, have emerged from posttraumatic amnesia (PTA) ... impaired self-awareness, defined as having a positive discrepancy of at least 2 points between participant and therapist ratings on the Awareness Questionnaire ... and observation of errors in performance of a cooking task;”	Participants with TBI and impaired self-awareness recruited from inpatient and community rehabilitation settings; Participants screened (n = 167); randomised: (n = 54); Completed: 36; Intention-to-treat analysis Video feedback group (n = 18): average age 42.7 years; gender: 4f, 14 m Verbal feedback group (n = 18): average age 41.6 years; gender: 4f, 14 m Experiential feedback group (n = 18): average age 37.5 years; gender: 0f, 18 m	All participants completed a meal preparation task (all videotaped) on 4 occasions. Video feedback group: participants watched their videotaped performance of the meal preparation task with the therapist; while viewing, the therapist encouraged the participant to retrospectively identify errors in task performance, observe areas of strength, and suggest compensatory strategies to be used in future sessions. The therapist and participant then verbally discussed any discrepancies in their ratings of the task performance. Verbal feedback group: the therapist followed the same guidelines for verbal discussion of discrepancies between ratings on the MIRS without viewing the videotape.	Experiential feedback group: no direct feedback provided following the meal preparation task. The participant and therapist separately completed the MIRS, and discrepancies and ratings were not discussed.	Primary outcome: improvement in awareness of number of errors made during meal preparation task; Secondary outcomes: AQ; WCST; WMS-III; SPIRQ; DASS-21	Video feedback group compared to experiential feedback group: fewer meal preparation errors (p < 0.001) (average 70.7% reduction (> >30% reduction in errors identified a priori to be clinically meaningful). Verbal feedback group average 20.7% and experiential feedback group average 37.6% mean reduction in errors over intervention period. Secondary outcomes: AQ p < 0.01; SPIRS ns, DASS-21 ns.
Wilson et al., 2005, UK; purpose: to examine if cognitive rehabilitation with a paging system is successful for people with TBI	RCT; power computation: none; time from TBI to starting therapy: 5.3 years follow-up: not stated; definition of TBI: “an interview and a short trial to see if they could (a) read a test message on the screen of the pager and (b) respond appropriately by pressing a button on the pager ... and reported to have memory and/or planning problems;”	Referrals from throughout UK (from clinical psychologists, OTs, STs, psychiatrists, organizations and disability services). TBI participants with memory and/or = planning/problems. Eligibles: 209; Randomised: 198; 173 completed baseline study and 63 identified as TBI; Completed: (n = 63); age range: 18 to 65 years; gender: 10f, 53 m No age or gender data for either Group A or B	Pager system (7 weeks) Participants received pager that would send messages reminding them to carry out everyday tasks (e.g., pick the children up from school). Only messages requested or agreed by the participant were selected for transmission. Messages were selected based on participants’ reported problems with memory or planning.	Wait list	Questionnaire about everyday memory, attention and other cognitive failures. Participants or carers asked to record daily whether or not targets had been achieved.	Achievement of targets: Baseline (without pagers): Group A 47%, Group B 48%; Group A Received pagers for 7 weeks: During last 2 weeks Group A 72%, Group B (waiting list) 49%, p < 0.001); Group B Received pager for 7 weeks: Group A 67%, Group B 74% (p < 0.001); The 81% of participants who completed all stages of the trial achieved significantly more targets achieved) with the pager than they had been in baseline phase. The paging system helped people with TBI carry out everyday tasks more efficiently and increased their level of independence.
Aerobic vs. stretching exercises
Kuroski 2017, USA. Compare aerobic vs stretching exercises	RCT; Power computation: 15/group for 1.25 effect size, alpha 0.05, power 0.9; time from TBI to starting therapy: 54 days; follow-up: 7 weeks; definition of TBI: American Congress of Rehabilitation, and 4-16 weeks of persistent symptoms;	Recruited from community, brain/head injury clinics and emergency departments,Cincinnati, Ohio; screened: 365; eligibles: 136 (102 refused, 54 not interested, 20 time commitment, 13 recovering, 15 other), 34 recruited; randomised: 30 (12 completed aerobic and 14 stretching intervention); Gender: cycling group 10 females, stretching 7 females	Using theory that “dysregulation in cerebral metabolism and cerebral blood flow may largely explain the sequelae” cycling: baseline: increase intensity until experienced symptoms or max 30 minutes; then 5-6 days/week at home up to 80% of symptoms experienced on previous weekly clinic assessment	Stretching: trunk, upper and lower extremities stretching, new exercises every 2 weeks	Post-Concussion Symptom Inventory	Self-rated PCIS: Cycling Group: pre-randomisation 23.93,; final assessment 4.17; Stretching Group: pre-randomisation 27.53, final 15.93; P = 0.036) Parent-rated PCIS: Cycling Group: pre-randomisation 25.86; final assessment 9.50; Stretching Group: pre-randomisation 24.79, final 10.79; no significant differences for groups after therapy Adherence to home exercise programme: greater in stretching group (p < 0.0001)

List of tests (with abbreviations): 4CRT = Four Choice Reaction Time Task; AMIPB = Adult Memory and Information Processing Battery; AQ = Sherer Awareness Questionnaire; BDI-II = Beck Depression Inventory; BSI = Brief Symptom Inventory; CFS = Standardised Cognitive Functioning Sum (Memory and Attention); CIQ = Community Integration Questionnaire; CSI = Caregiver Strain Index; DASS-21 = Depression Anxiety Stress Scales; D-KEFS = Delis-Kaplan Executive Function Systems Hayling sentence completion, D-KEFS Trail Making-, D-KEFS Category switching; D-KEFS Color-word inhibition task-3; DSM = IV = Diagnostic and Statistical Manual IV; FAS-COWAT = FAS-Controlled Word Association Task; FSE = Dikmen FSE Daily function; GHQ = General health Questionnaire; HADS = Hospital Anxiety and Depression Scale; ICD-10 = International Classification of Diseases 10; Interest Checklist (Swedish Version); IPQ-R + Illness Perception Questionnaire-Revised; ISEL = Interpersonal Support Evaluation List; Job Satisfaction = Sikmovici Job Satisfaction Checklist (Swedish version); LES = Life Experience Survey; Life-3 = Life-3 Quality of Life Rating; LiSat-11 = Life Satisfaction Questionnaire; LNS = Letter Number Sequencing Task; M2PI=Mayo-Portland Participation Index; PASAT = Paced Auditory Serial Addition Test; PCL = Problem Checklist: PCSQ = Post-Concussion Symptoms Questionnaire; PHQ-9 = Patient Health Questionnaire; PSI = Problem Solving Inventory; PSQ = Problem Solving Questionnaire; PSRPT = Problem Solving Role Play Test; PTSD = PTSD Checklist; Role Checklist = Oakley Role Checklist (Swedish Version); RPQ = Rivermead Post-Concussion Symptoms Questionnaire; RSAB = Rating Scale of Attentional Behaviour; RSES = Rosenberg Self-Esteem Scale: RUFF = Ruff and Selective Attention Test; SART = Sustained Attention to Response Task; SAT = Selective Attention Task; SCL-90R = Symptom Check List-90R General Symptom Index; SCWT = Stroop Color-Word task; SDMT = Symbol Digit Modalities Test; SF-36 = Short-Form Health Survey; SIP = Sickness Impact Profile; SMQ = Sunderland Memory Questionnaire; SPIRQ = Self Perceptions in Rehabilitation Questionnaire; STAI = State-Trait anxiety Inventory; TEA = Test of Everyday Attention; TMT = Trail Making Test; TOSL = Test of Strategic Learning; Watson-Glaser Critical Thinking Appraisal; WAIS-III = Wechsler Adult Intelligence Test 3rd ed.; WCST = Wisconsin Card Sorting Test; Wechsler Digit Backward; WMS Logical Memory; WMS III = Wechsler Memory Scale 3rd ed.; WVCT = Weinberg Visual Cancellation Test; Will Temperament Scale. C-RCT = cluster-randomised controlled trial.

Table 3

RCTs of interventions for mild to moderate brain injury/concussion

Author, date, country, purpose	Study design	Population	Intervention	Comparison	Outcome measures	Results
Cognitive therapy interventions
Tiersky 2005, USA; purpose: CBT to increase coping; attention, memory, information processing	RCT, wait-list; power computation: none; time from TBI to starting therapy: intervention group 5, control 5 years; f ollow-up 3 months; definition of TBI: “subjects with mild TBI met the definition proposed by the Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine” “Those with moderate TBI must have had a Glasgow Coma Scale (GCS) score between 9 and 12 at the time of injury and a loss of consciousness (LOC) between 30 minutes and 4 hours” “a Disability Rating Scale (DRS) between 1 and 5 at study inclusion”	Eligibles 277 (others excluded for not meeting inclusion criteria, psychiatric disorder, no transport); randomised: 29 (Treatment 14 Control 15); completed: 20 (11 in treatment group, 9 controls); completed 20; not intention-to-treat analysis; Age: Treatment: 47.55(11.78) Control: 46.00(9.35) Total sample (n = 20): 46.85(10.51); gender: 11f, 9m	Experimental group: 50 minutes of individual cognitive-behavioural psychotherapy + 50 minutes of individual cognitive remediation, 3 times a week for 11 weeks. Cognitive remedial training focused on: (1) attention and information processing, (2) memory, (3) organization and problem-solving skills; CBT focused on: (4) increase effective coping behaviours, (5) reduce stress, (6) prevent relapse, (7) cope with feelings of loss; 50 minutes 3x/week×11 weeks	Control group: Wait-list (received treatment after conclusion of follow-up); control group participants met with principal investigator×45 minutes, or spoke on phone 2 or 3 times	Main Outcome Measures: SCL-90R GSI, Depression and Anxiety subscales, PASAT, AQ; Secondary Outcome Measures; SCL-90R Somatization, RAVLT, ACFI, CRI, CIQ	Intervention group improved on divided auditory attention (PASAT) (P = 0.011); SCL-90R anxiety (p = 0.031); depression subscale (p = 0.029); GSI (p = 0.046) compared to control; but CRI and AQ (ns); SCL-90R Somatization, RAVLT, ACFI, CRI,CIQ (all ns)
Twamley 2014, 2015 USA; purpose: Cognitive Symptom Management + supported employment compared to supported employment + therapist attention	RCT; power computation: none; time from TBI to starting therapy: supported employment + CogSMART group 3.6 years, Supported Employment 5 years; follow-up: 3 months; assessment of return to work within 14 weeks; definition of TBI: “mild to moderate TBI (loss of consciousness for <24 hours and posttraumatic amnesia for <7 days), documented in a prior neuropsychological evaluation and confirmed by a structured interview;”	eligibles 257 US veteran soldiers (excluded: 157 not meet inclusion criteria, 12 declined, 12 moved, 10 did not return phone calls); randomised: 50; completed: (34; Supported employment group n = 16; enhanced supported employment group n = 18); intention-to-treat analysis; average age: Supported Employment + CogSMART 29, Supported Employment 34 years; gender: 2 f, 34m	12 weeks supported employment (2 visits/week); plus Compensatory cognitive training 1 visit/week) (psychoeducation, strategies to improve sleep, fatigue, headache, attention, memory, attention, learning and memory, executive functioning)	12 weeks supported employment (2 visits/week);	Main Outcome Measures: Attained competitive work within 14 weeks: MIST; WAIS-III Digit Span Scaled Score; CVLT-II; D-KEFS; WCST-64; NSI; CAPS; HAM-D; QOLI-Brief; Attained competitive work within 14 weeks	Both groups: 13/25 attained competitive work within 14 weeks (ns) Supported + Compensatory group: improved more on Neurobehavioral Symptoms Inventory (p = 0.01) and Memory for Intentions Screening (p = 0.05); all other outcome measures n,s
Virtual environment. memory aids or pagers
Man et al., 2013, China/USA; purpose: to examine the effectiveness of an artificial intelligent virtual reality (VR)- based vocational problem-solving skill training programme designed to enhance employment opportunities for people with TBI. ROSANA	RCT; Power computation: for alpha = 0.05, power = 0.8, effect size 0.4, 22 per group required; time from TBI to starting therapy: not stated; follow-up: 1 and 3 months; 6 months only for job status information; definition of TBI: Mild: post-traumatic amnesia <1 hour, Glasgow Coma Scale 13–15 and loss of consciousness <15 minutes; Moderate: post-traumatic amnesia 1–24 hours, Glasgow Coma Scale 9–12, and loss of consciousness <6 hours;	Participants with mild-to-moderate TBI were recruited through various hospital and community rehabilitation facilities and centres in Hong Kong; age between 18–55 years. 50 assessed for eligibility; randomised (n = 50). AIVTS group (n = 25; completed n = 20): PEVTS group (n = 25; completed n = 20): age range: 18–55; gender: not stated	Artificial intelligent virtual reality-based vocational training system (AIVTS): interactive program, enabling the user to exercise direct control over a virtual environment. The training program was designed by dividing the clerical work process into a series of tasks that required participants to use their problem-solving abilities. 12 sessions of 20–25 minutes each. The structure and contents of the two programs were similar.	Conventional psycho-educational vocational training programme (PEVTS): vocational skill training developed for the study were for clerical work and pertinent to the individual. The programme consisted of the same number of training sessions and had the same problem-solving training content and structure as AIVTS. However, PEVTS was delivered in the form of a training manual under the supervision of a vocational trainer and by practicing routines, tutorials with specific instructional branches, simulations and instructional games on problem-solving. Feedback was given to the trainee by a trainer verbally.	Main Outcome Measures; WCST; TOL; VCRS; return to employment	AIVTS group compared to PEVTS group: WCST errors (p = 0.02); WCST conceptual level response (p < 0.01); No differences for TOL, WCTS perseverative errors, VCRS or return to work

List of tests (with abbreviations): ACFI = Assessment of Client Functioning Inventory; AQ = Attention Questionnaire; BVRT = Benton Visual Retention Test; CAPS = Clinically Administered Posttraumatic Stress Disorder Scale; CFT = Rey-Osterrieth Complex Figure test; CIQ = Community Integration Questionnaire; CRI = Coping Response Inventory, Problem-Solving; CVLT-II = California Verbal Learning Test- 2nd ed.; D-KEFS = Delis-Kaplan Executive Function Systems; HAM-D = Hamilton Depression Rating Scale; MIST = Memory for Intentions Screening Test; NSI = Neurobehavioral Symptom Inventory; QOLI-Brief = Quality of Life Interview – Brief Version; PASAT = Paced Auditory Serial Addition Test; RAVLT = Rey Auditory Learning Test; SCL-90R = Symptom Check List-90R General Symptom Index, Depression, Anxiety and Somatization scales; SRT = Selective Reminding Task; TCF = Taylor Complex Figure test; Test; TLT = Ruff-Light Trail learning Test; TOL = Tower of London Test; VCRS = Vocational Cognitive Rating Scale; WAIS-III Digit Span Scaled Score; WCST = Wisconsin Card Sorting Test; WMS-LM = Wechsler Memory Scale-Logical Memory subtest.

3.2 Description of included studies and participants

The total number of participants randomised was 909 and the number who completed the RCTs 822 (90%). However, higher attrition rate occurred in eight studies (45% in Ashman, Cantor, Tsaousides, Spielman, & Gordon, 2014; 33% in Schmidt, Fleming, Ownsworth, & Lannin, 2012; 31% in Tiersky et al., 2005; 29% in Silverberg et al., 2013; 23% in Rath et al., 2003; 21% in Bédard et al., 2013; 13% in Kuroski et al., 2017; and 10% in McMillan, Robertson, Brock, & Chorlton, 2002). In the remaining six RCTs 100% of those randomised completed the trial. The number of eligibles was reported for nine trials and the main reasons apparent eligibles were not randomised were that they were not TBI, stated they had recovered or they declined participation. For the thirteen RCTs that reported gender data the average was 31% female. For the eleven studies that reported an average age the average was 38 years (not including the 30 adolescents in Kurowski et al., 2017) and for the three that reported only age ranges one included participants 18–55 and two 18–65. For the ten RCTs that reported the interval between the concussion injury and beginning therapy one began after <6 weeks (Silverberg et al., 2013), one after 2–8 weeks (Andersson, Emanuelson, Björklund, Stålhammar, 2007), one after eight weeks (Kurowski et al., 2017), one after 6 months (Vas et al., 2015), two at one year (McMillan et al., 2002; Rath et al., 2003) and four after 4–5 years (Schmidt et al., 2013; Wilson, Emslie, Quirk, Evans, & Watson, 2001; Tiersky et al., 2005; Twamley, Jak, Delis, Bondi, & Lohr, 2014). For the eleven that stated the follow-up period it ranged from 6 weeks (Kurowski et al., 2017), three months (Ashman et al., 2014; Bédard et al., 2014; Man et al., 2013; Silverberg et al., 2013; Tiersky et al., 2005; Twamley et al., 2014; Vas et al., 2015); to six months (Rath et al., 2003); and twelve months (McMillan et al., 2002; Andersson et al., 2007).

3.3 Interventions

Eight RCTs used cognitive behavioural therapy (CBT) (Ashman et al., 2014; Bédard et al., 2014; McMillan et al., 2002; Rath et al., 2003; Silverberg et al., 2013; Vas et al., 2015; Tiersky et al., 2005; Twamley et al., 2014); four used videotape, pagers or personal digital assistants (Dowds et al., 2011; Schmidt et al., 2013; Wilson et al., 2001; Man, Poon, & Lam, 2013), one physical therapy (Kurowski et al., 2017) and one referred selected patients to health professionals (Andersson et al., 2007).

The CBT interventions focused on improving two areas (task performance and sense of well-being) but within each area were very varied. Task-oriented strategies included interventions for memory, attention, spatial integration, information processing, processing speed, executive function, reasoning, cognitive restructuring, error correction, planning and mastery. Interventions to increase the sense of well-being included social outreach, relaxation, meditation, yoga, awareness of thoughts, breathing, reducing maladaptive beliefs, coping behaviours, increasing perceived control, innovation, social outreach, relaxation, mindfulness, stress reduction, coping with feelings of loss due to the concussion, relapse prevention, reduction in self-critical dialogues, and strategies to improve sleep, fatigue and headache.

The four interventions which used electronic devices each had unique protocols. Dowds et al., 2011 compared paper and two different personal digital assistants to increase the rate of timely completion of tasks, Schmidt et al., 2012 videotaped each participant’s preparation of four meals and provided feedback, Wilson et al., 2001 used pagers to remind patients to perform daily tasks such as picking up their children, and Man et al., 2013 compared an “artificial intelligent virtual reality-based vocational training system” to a “conventional psycho-educational vocational training program” to divide clerical tasks into a series of steps and problem solve them.

Eleven RCTs included only mTBI patients. We included three RCTs (Tiersky et al., 2005; Twamley et al., 2014; Man et al., 2013) of mild and moderate TBI (Table 3) to assess if the authors proved it is appropriate and feasible (e.g., if resources such as trainers or evaluators are limited) to use the same interventions with both mild and moderate TBI patients. However, these RCTs did not report the results separately for those with mTBI and moderate TBI and the authors did not report whether the interventions used were appropriate and worked equally well for both groups.

3.4 Definitions of traumatic brain injury/concussion used in the included RCTs

Mild traumatic brain injury (mTBI) and concussion are often used interchangeably, and there are two key definitions of mTBI and one of concussion (Table 1). Only four RCTs included in this review used any of these definitions and all four chose the American Congress of Rehabilitation definition (Andersson et al., 2007; Silverberg et al., 2013; Tiersky et al., 2005; Kurowski et al., 2017).

However, the remaining nine studies each used a unique definition (Tables 2 and 3). The following examples illustrate the variety of definitions used in the RCTs that assessed their subjects as having mTBI: “loss of consciousness or period of being dazed of confused or a period of posttraumatic amnesia or clinical signs of altered neurological function” (Ashman et al., 2014); “problems of attention on neuropsychological testing, or who reported attentional problems in everyday life ... no previous head injuries or major neurological disease ... between three months and one year post-injury and living at home, no significant language problems, fully oriented in time, place, and person ... aware of cognitive problems, including concentration difficulties” (McMillan et al., 2002); and “participants were required to meet minimum ”basic skill “ criteria ... the ability to sustain attention for an hour-long session, take organised notes, give and receive feedback, state cognitive strengths and weaknesses, and relate to others with adequate social skills” (Rath et al., 2015).

The RCTs that grouped together mTBI and moderate TBI each used different definitions: “Those with moderate TBI must have had a Glasgow Coma Scale (GCS) score between 9 and 12 at the time of injury and a loss of consciousness (LOC) between 30 minutes and 4 hours” “a Disability Rating Scale (DRS) between 1 and 5 at study inclusion” (Tiersky et al., 2005); “loss of consciousness for <24 hours and posttraumatic amnesia for <7 days, documented in a prior neuropsychological evaluation and confirmed by a structured interview” (Twamley et al., 2014); and “post-traumatic amnesia 1–24 hours, Glasgow Coma Scale 9–12, and loss of consciousness <6 hours” (Man et al., 2013). The more recent authors neither noted the problem of non-standardized definitions of mTBI/concussion nor attempted to standardize on the most widely used guideline definition.

It is likely that data from team sports injuries will increasingly use the SCAT forms because they have been endorsed by the Federation of International Football Associations (FIFA), the International Ice Hockey Federation (IIHF) and the International Rugby Board (IRB) as their official assessment tool, so it is important for researchers to agree on one definition for mTBI/concussion.

3.5 Outcome measures in the included RCTs

Two studies used a single outcome measure: Dowds et al., 2011 compared the percentage of timely task completion comparing two personal digital assistants and paper, and Wilson et al., 2005 the percentage of successful reminders to complete everyday tasks such as picking up the children using a pager to no intervention, but most RCTs pre-specified multiple outcome measures. The 14 RCTs altogether used 80 individual assessment scales; one scale was used four times (WCST), the BDI = II three times and four scales were used twice (AQ, D-KEFS, PASAT, and SCL-90R), and thus meta-analysis of the outcomes is not possible.

3.6 Risk of bias (Figs. 3 and 4)

Randomization: 43% were at low risk (a strong method was used such as computer assignment by an individual unaware of the study) and 57% unclear (no statement); Concealment: 14% concealed assignment from the researchers, 79% unclear, 7% did not; Blinding of Participants and Personnel administering the intervention: 21% blinded, 43% unclear, 36% not blinded; Blinding of Assessors: 57% blinded, 14% unclear, 29% not blinded; Attrition: 64% low risk from attrition after randomization, five (43%) had attrition rates >20% and in 29% of these it was unclear what the level of risk was and in 7% was high risk; Selective reporting, 0%.

Fig.3

Risk of Bias Summary.

Fig.4

Risk of Bias Graph.

3.7 Outcomes (Tables 2 and 3)

As a measure of effect eleven authors reported means and standard deviations with probabilities (Andersson et al., 2007; Ashman et al., 2014; Bédard et al., 2013; Dowds et al., 2011, Man et al., 2013; McMillan et al., 2002; Silverberg et al., 2013; Tiersky et al., 2005; Twamley et al., 2014; Vas et al., 2015; Wilson et al., 2005) but all for different outcome measures which thus could not be meta-analysed. Five authors computed effect sizes (Ashman et al., 2014; Kurowski et al., 2017; Rath et al., 2003; Silverberg et al., 2013; Twamley et al., 2014) all for different outcome measures, and one author Incidence Rate Ratios with 95% Confidence Intervals (Dowds et al., 2011). One author reported the results of t-tests of means but without the actual means or standard deviations (Rath et al., 2003).

Eleven RCTs (Table 3) included individuals with mTBI. All six that used CBT had significant positive changes on multiple outcome measures at p < 0.05 or better (Ashman et al., 2014 on 4 of 6; Bédard et al., 2013 on 5 of 5; McMillan et al., 2002 on 2 of 10, Rath et al., 2015 Innovative group on 9 of 16 and Conventional group on 4 of 16; Silverberg et al., 2013 on 4 of 8; and Vas et al., 2015 on 14 of 14). All three RCTs that used devices such as pagers or video feedback all three had significant positive changes on outcome measures at p < 0.05 or better. For Dowds et al., 2011 using the Palm personal digital assistant, timely task completion improved from 27% at baseline to 56% after using the PDA (p < 0.0005), for Wilson et al., 2005 from 47% at baseline to 70% after using the PDA (p < 0.001), and for Schmidt et al., 2013 a 71% reduction in errors preparing meals (p < 0.001). The one RCT that tested cycling vs. muscle stretching found a significant improvement reported by the patients (p = 0.036) on the Post-Concussion Symptom Inventory but no significant difference as rated by the primary caregiver (Kurowski et al., 2017). The one RCT (Andersson 2007) [34] that referred individuals to health specialists had no significant effects (and had substantial attrition).

Three RCTs (Table 3) included both mild and moderate TBI individuals. The two which used CBT had significant positive changes on outcome measures (Tiersky et al., 2005 on 4 of 9 outcome measures and Twamley et al., 2014 on 2 of 9) and the one RCT that used virtual reality training (Man et al., 2013) on 2 of 7. In this group were the only two RCTs that assessed return to work and neither RCT found any significant differences in rates of return to work between the two intervention groups. Twamley et al., 2014 reported that both intervention groups achieved the same return to full-time competitive employment (13/25 individuals) and Man et al., 2013 that after six months 60% in the artificial virtual reality group were unemployed and 80% in the conventional psychoeductional group, but neither study used a no-intervention control.

4 Discussion

4.1 Strengths and limitations

The strongest aspect of this group of studies is that most interventions were based on well-researched theories and their implementation was appropriately measured and clearly described.

There are many limitations: (1) The large number of different definitions of mTBI/concussion made the included study populations non-comparable. (2) None of the authors built on the interventions or findings of previous authors and each intervention was unique, (3) No RCT tested the intervention of a previous RCT in a different population to check reproducibility of findings or extend generalizability (e.g., Twamley et al., tested their intervention only on veteran soldiers, nearly all males). (4) Some studies used interventions with multiple intervention components whose individual effects could not be disentangled (e.g., Bédard et al., 2013 used mindfulness cognitive therapy with meditation breathing exercises, yoga, awareness of thoughts and feelings, acceptance of disability, staying in the present, daily meditation, and improvement in attention, concentration and memory) and Ashman et al., 2014 multiple interventions that were similar to Bédard’s but not directly comparable. Other RCTs used a single intervention: McMillan et al., 2002 used only breathing-based attentional control training and Schmidt et al., 2013 focused only on the preparation of four meals, but no other author tested these interventions, (5) Several studies had high attrition rates (Ashman et al., 2014 45%; Schmidt et al., 2012 33%; Tiersky et al., 2005 31%; Silverberg et al., 2013 29%; Rath et al., 2003 23%; Bédard et al., 2013 21%; McMillan et al., 2002 10% and Kurowski et al., 2017 9%) and none of these authors provided a differential attrition analysis to prove that dropouts from the intervention and control groups were equally balanced on attributes that could be related to the outcome measures. The generalizability of the RCTs to other populations is affected by three aspects of study design: (6) only eight RCTs reported the numbers of potential eligibles initially considered or assessed, (7) the large number (80) of outcome assessment measures made the studies non-comparable and prevented meta-analysis, and (8) small sample sizes (average 65 randomised).

Dizziness, balance and ocular dysfunction following mTBI/concussion are often very troubling, may require a long period to improve and often involve multidisciplinary teams of physiotherapists, occupational therapists, speech-language pathologists or vestibular specialists. A 2016 systematic review of vestibular rehabilitation identified only two RCTs and eight non-randomised studies (Murray, Meldrum, & Lennon, 2017). One small RCT (n = 28) found that 11/15 (73%) of the treatment group and 1/14 (7%) of the control group were medically cleared within eight weeks of commencing treatment. (Schneider et al., 2014).

There has been extensive discussion of whether rest or exercise promote more rapid rehabilitation. A systematic review identified three studies of rest and twelve of treatment (Schneider et al., 2013) and did not identify any significant results of clinical applicability. A MEDLINE search identified no RCTs of speech language pathology, occupational therapy or speech- language therapy and mTBI/concussion in sports.

4.2 Recommendations for research

(1) Future studies need to use the same definition of concussion or mTBI (the American Congress of Rehabilitation criteria were used by four of the included studies). (2) Only five RCTs made a power computation to estimate the needed sample size (Anderson et al., 2007; Bédard et al., 2014; Schmidt et al., 2013; Man et al., 2013; Kurowski et al., 2017). (3) The ability to generalise from RCTs needs to be improved. Studies tend to use patients referred to rehabilitation clinics. The average age of the patients in the current studies is 38, and young individuals are underrepresented. Only one RCT included sports injuries (Kurowski et al., 2017) and more RCTs need to focus on the rehabilitation of sports injuries and the internationally accepted SCAT3 criterion for sport concussion needs to be added to the baseline and outcome measures. The largest possible feasible universe of concussed/mTBI candidates should be identified, the most widely used definition of concussion/mTBI should be a standard definition and utilized to identify mTBI individuals, who represent 80% of traumatic brain injured individuals (Kurowski et al., 2017). (4). Every effort should be made to motivate individuals to stay in the trial until completion. (5). The key problems after mTBI/concussion are (a) slowed processing of information (Ponsford, Bayley et al., 2014; Spikman et al., 1996; Willmott et al., 2009), (b) reduced working memory (Vallat-Azouvi, Weber, Legrand, & Azouvi, 2007; Velikonja et al., 2014), (c) decreased sustained attention and difficulty with multiple steps, changing demands and dual tasks (Robertson, Manly, Andrade, Baddeley, & Yiend, 1997; Ziino & Ponsonby, 2006; Tate et al., 2014; Togher et al., 2014), (d) fatigue, (e) sleep disturbances, (f) increased visual sensitivity, (g) increased auditory sensitivity, and (h) anxiety (Bayley et al., 2014). RCTs need to test the effect of interventions separately on these key consequences of concussions so that therapies with statistically significant positive results can be selected to improve the patients’ most concerning problems. (6). The execution of trials needs to improve: only 43% reported a strong method of randomization, 14% concealment of allocation from the researchers, 21% blinding of participants and personnel administering the intervention, 57% blinding of assessors, 64% low risk from attrition after randomization and no study with attrition reported a differential attrition analysis to prove that dropouts were unrelated to the outcome measures. (7) Outcome measures should be standardized on an optimal set instead of the 80 different outcome measures used in the RCTs included in this review. (8) Only two studies were clearly described as cluster-randomised RCTs (C-RCTs) and it is unknown whether individual or group therapy or a combination is optimal. (9) All studies should assess return to work of participants and how the intervention facilitates that return. (10) Physiotherapy is a key area of rehabilitation for many concussed patients, but the RCT literature is too scarce to permit a systematic review.

5 Conclusions

No study used the interventions of previous studies and improved them or tested them in different populations to increase generalizability, only four used the same definition of concussion, and a total of 80 different outcome measures were used: WCST was used four times, BDI = II three times and AQ, D-KEFS, PASAT, and SCL-90R two times each, and thus meta-analysis of the outcomes is not possible.

Eleven RCTs (Table 2) included individuals with concussion/mild traumatic brain injury. All six RCTs that evaluated CBT found significant positive changes on multiple outcome measures at p < 0.05 or better. All three RCTs that used digital assistants, pagers or video feedback had significant positive changes on outcome measures at p < 0.05 or better. In the study by Dowds et al., 2011 timely task completion improved from 27% at baseline to 56% after using the Palm personal digital assistant (p < 0.0005). In the study by Wilson et al., 2005 task achievement improved from 47% at baseline to 70% after using the PDA (p < 0.001). In the Schmidt et al., 2013 study errors in preparing the four meals declined by 71% (p < 0.001). The one RCT of adolescents found significant improvement in the cycling group on the Post-Concussion Symptom Inventory compared to the group which practised muscle stretching (p = 0.036). The one RCT that referred individuals to health specialists had no significant effects (and had substantial attrition) (Andersson et al., 2007).

Of the three RCTs (Table 3) that included both mTBI and moderate TBI individuals, both RCTs that used CBT (Tiersky et al., 2005; Twamley et al., 2014) and the RCT that used virtual reality training (Man et al., 2015) had significant positive changes on outcome measures. The only two RCTs that assessed return to work are in this group and both RCTs found no differences in return to work between the two intervention groups Twamley et al., 2014 reported that both intervention groups achieved the same return to full-time competitive employment (13/25 individuals) and Man et al., 2013 that after six months 60% of those in the artificial virtual reality and of those 80% in the conventional psycho-education group were unemployed, but neither study used a no-intervention control.

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