Traumatic brain injury (TBI) is a common, preventable, and disabling health condition with heterogeneous aetiology, type, severity, and outcomes. Ongoing challenges in TBI care are reflected by rapidly growing literature in the prevention, assessment and treatment of TBI, especially in sports concussion and blast-related TBI. Recent advances include TBI modelling, to predict outcomes of TBI and to improve future data collection, by the International Mission on Prognosis and Analysis of randomized Controlled Trials in TBI (IMPACT) [1] and Transforming Research and Clinical Knowledge in Traumatic Brain Injury pilot (TRACK-TBI) [2], respectively. In comparison, there is a lack of clarity and standardization in the diagnostic criteria, severity grading, and nomenclature to describe TBI, which could improve many aspects of TBI care, especially in developing targeted therapies for TBI [3,4]. TBI is currently defined as ‘an alteration in brain function, or other evidence of brain pathology, caused by an external force’ [5].

Glasgow Coma Scale (GCS) was introduced for clinical monitoring following TBI [6], and was subsequently used to grade TBI severity [7]. Inadequacies of GCS for this latter purpose is widely recognised [8,9], but no clear alternative exists. PTA is an excellent prognostic marker [10], and was incorporated into the criteria for mild TBI by the American College of Rehabilitation Medicine (ACRM) [11]. However, there is no consensus in the literature for the selection of clinical features for TBI diagnosis and severity grading [3]. There is no standardized nomenclature of TBI subtype, which may be based on the history, clinical features and imaging findings [12].

Treatments for TBI patients are varied and complex. Evidence to support early rehabilitation interventions for definable stages of recovery for patients’ emerging from traumatic coma (such as, early application of awareness stimulation techniques), and management of PTA (reducing agitation by environmental modification) is unclear. Treatments for TBI address cardiovascular disorders (e.g. hypertension); respiratory issues; fever; bladder and bowel dysfunction; swallowing and nutrition; and spasticity management. Others target thrombophlebitis; contractures; fractures; peripheral nerve injuries; and heterotopic ossification. Despite a range of cognitive remediative therapies that are cornerstone of rehabilitation, and specific interventions for movement disorders in TBI (such as tremors, rigidity, dystonia, chorea, or tics), the evidence to support these interventions needs clarification.

The objectives of this overview are [1] to critically examine the literature for diagnostic criteria, severity grading, and types of TBI, [2] to present existing evidence for treatment in TBI, and [3] to consider future direction in TBI diagnosis and management.

Search strategy

Firstly, a comprehensive electronic search of Medline, Allied and Complementary Medicine (AMED), Biological Abstracts, Health and Psychosocial Instruments, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO identified studies in TBI diagnosis. Secondly, a further targeted search of the CENTRAL identified studies for TBI rehabilitation interventions. Comprehensive search strategy; and inclusion and exclusion criteria are outlined in Table 1. No restrictions were applied with respect to research design. Medical subject headings (MeSH) search terms were used for all databases. A key word search was used if the medical subject heading was unavailable.

Table 1: Search strategy, inclusion and exclusion criteria for the systematic review in traumatic brain injury (TBI) diagnostic criteria and rehabilitation.

Study selection

Screening of all titles and abstracts from the search strategy identified studies for closer examination. Full texts of included studies were obtained for further assessment to determine whether the study met the inclusion or exclusion criteria inclusion into the evidence synthesis. For the rehabilitation treatment section all current and updated systematic reviews in CENTRAL were included. Wherever comprehensive updated systematic review were identified, search for individual studies within those reviews was not conducted.

Data extraction

Data extraction was conducted for all included studies for TBI diagnosis using a standard proform a consisting of:author; publication year; study location; study design; sample size; TBI type and severity; key findings; recommended outcome measures or criteria for TBI; and key sources for recommendations. The pro forma for TBI rehabilitation consisted of: author; publication year; injury type; intervention; key findings; and level of evidence. For the rehabilitation treatments, all interventions, type of injury, study year and key findings were examined.

Data synthesis

A wide range of terminologies described similar clinical problems in TBI in the literature, and therefore, similar concepts were grouped together for convenience: ‘altered conscious state’ to include ‘disordered consciousness’, ‘dazed’, ‘disorientated’, ‘confused states’; and ‘PTA’ to include ‘amnesia of blow’.

Quality assessment and analysis of the included studies

Quantitative analysis of included studies was not possible due to the heterogeneity of studies in terms of intervention and outcomes measured. Therefore results were presented qualitatively. To determine level of evidence for treatment in TBI, the National Health and Medical Research Council (NHMRC) Levels of Evidence and Grades for Recommendations for Developers of Guidelines 2009 [13] was used. All detailed information from the included studies was tabulated.

Systematic search

For TBI diagnosis, from the initial search (n=972), thirteen studies were included, and a further five studies were identified for inclusion into the evidence synthesis based on the inclusion and exclusion criteria (Figure 1) to a total of nineteen studies in the areas of blastrelated TBI (n=1); concussion (n=2); mild TBI (n=6); ‘GCS 13’ (n=1); severe TBI (n=3); and all TBI (n=6). Data synthesis based on the pro forma is presented in Table 2.

Figure 1: PRISMA outlining search process for studies in TBI diagnostic criteria [36].

Table 2: Summary of the studies in the diagnostic criteria for traumatic brain injury (TBI).

For TBI treatment, the targeted search strategy identified 32 reviews, of which 25 systematic reviews evaluated various rehabilitation interventions in the TBI population, and are tabulated in Table 3.

Table 3: Summary of the systematic reviews in the Cochrane Central Register for the treatment of traumatic brain injury (TBI).

Characteristics of included studies

TBI diagnosis

Consensus for the lowest threshold for TBI diagnosis: The concept of a lowest threshold for diagnosing TBI is significant, firstly, due to a lack of clear consensus in the diagnostic criteria for mild TBI, and secondly, to avoid over-diagnosis in TBI given increasingly sensitive methods for identifying brain dysfunction following head trauma. Ambiguity in TBI diagnosis could also contribute to underdiagnosis of TBI due to lowered community awareness; presentations to hospitals; and accurate documentation of cases [14]. Four of the included studies in TBI diagnosis specifically addressed this issue: two systematic reviews [3,15]; a consensus statement [5]; and a database analysis [16] (Table 4).

Table 4: Summary of lowest thresholds for diagnosingtraumatic brain injury (TBI) in the literature.

There is general agreement that a clear mechanism and suspicion of injury, plus a minimum of one significant clinical feature of TBI comprise this lowest threshold. PTA was the only agreed and emphasised criteria for the lowest threshold for diagnosing TBI by all four studies [3,5,15,16]. As expected, GCS was not criteria for the lowest threshold, being a specific but not a sensitive marker of TBI [15]. There was no consensus over the significance of other clinical features, which were proposed as a diagnostic criteria for TBI, and these were: on history – loss of consciousness [3,5,16], or seizure [3]; on examination – altered consciousness [3,5,15], focal neurological deficit [3,5]; and on imaging – intracranial lesion [3,5,16] or skull fracture [5,16].

Consensus for severity grading in TBI: Accurately diagnosing TBI severity has widespread implications for public health, clinical research, and clinical care of persons with TBI. Eleven studies specifically discussed severity grading system for TBI based on narrative reviews (n=2) [4,17]; systematic reviews (n=2) [3,18]; consensus (n=1) [5]; survey of clinicians (n=1) [8]; and clinical studies including retrospective data reviews (n=5) [16,19-22].

For the purpose of evidence synthesis for TBI grading, we considered their comments but did not explicitly incorporate studies with: no clear alternative grading system [4,8]; recommendations for sub classification within mild TBI [18,19] or severe TBI [21] – which were beyond the scope of this study. Recommendations by the remaining six studies are presented in Table 5.

Table 5: Summary of traumatic brain injury (TBI) severity grading in the literature.

In the included studies, GCS was the most common basis for TBI severity grading [3,17,18,20]. However, there was no consensus for GCS 13, whether this is mild or moderate TBI, despite a metanalysis demonstrating poor outcomes in GCS 13 [20]. Duration of loss of consciousness (LOC) and PTA were included for severity grading by two studies citing the same ACRM position statement [3,16]. There was no agreement over the role of: radiological findings of skull fractures or intracranial lesions [3,16]; Abbreviated Injury Score for head (AIShead) [22]; or neurological abnormality [3], for determining TBI severity. There was no agreement for timing of GCS assessment for severity grading.

Consensus for nomenclature for TBI types: The vast range of potential mechanism of injury and the resulting TBI makes nomenclature for describing types of TBI a challenge, and a potential barrier to developing targeted therapies for TBI [12]. Six studies were included for the nomenclature in TBI: in concussion – a consensus statement [23] and a narrative review [24]; in blast-related TBI – a narrative review [25]; and in TBI, two consensus papers [5,12], and one narrative review [26]. Nomenclatures for TBI in the studies are presented in Table 6.

Table 6: Summary of nomenclature for traumatic brain injury (TBI) types in the literature.

There was no single comprehensive nomenclature system for TBI types in the literature. Each study emphasized different aspects of the injury mechanism or outcomes to describe the TBI type, which were: the context of injury – being sports in concussion [23]; the type of force – being blast-related [25], acceleration-deceleration, or blunt [5]; the distribution of force – being focal or diffuse [17]; the impact of the force – being closed or open, or penetrating [26]; or the pathoanatomical diagnosis – such as skull fractures of intracranial lesions [12]. No study provided clinical correlations of their classification system to support the clinical relevance or superiority of their proposed classification structures.

Rehabilitation interventions in TBI: The current evidence for various rehabilitation interventions in TBI were categorized according to study design using evidence defined by the National Health and Medical Research Council (NHMRC) programme for intervention studies[13] (see Table 3).

A rehabilitation approach to TBI includes a wide spectrum of treatment and use of different interventions. However, many interventions have not yet been carried into comprehensive programmes and are provided often as individual interventions. Based on the NHMRC levels of evidence there is strong evidence for the effectiveness of psychological interventions such as attention training and cognitive interventions after TBI [27]; for nutritional support for improved survival and disability outcomes [28]; and hyperbaric oxygen therapy for reduction of risk of death after TBI [29]. There is moderate evidence for cognitive behavior therapy for managing stress after mild TBI [30]. For all other interventions the evidence is limited or insufficient due to lack of studies in the area. These include: speech therapy for dysarthria; vocational rehabilitation; hypothermia treatment; sensory stimulation programmes; hyperventilation therapy; and use of acupuncture in TBI.

This review provides an overview of literature on the diagnosis and rehabilitation interventions in TBI. Current approach to diagnosing TBI lacks clarity in its structure, and there is limited consensus for current systems in use, with its flow-on effect into the quality of epidemiological data, and acute and long term outcomes in TBI. This is a major issue which needs to be addressed with an international consensus approach, and clinical data to support the recommendations. Although a plethora of rehabilitation interventions are available for TBI population, the evidence to support many is lacking and are discussed below.

Lowest threshold for TBI

In the absence of unified diagnostic criteria for mild TBI, the lowest threshold for TBI diagnosis is useful. Following head trauma, PTA is a specific and agreed diagnostic criterion for TBI. The significance of other structural or functional changes remains unclear, and highly sensitive diagnostic approaches should be carefully correlated with clinical outcomes for their relevance. Excessive or missed diagnoses of TBI should be minimized to prevent psychosocial burden; and to avoid ambiguous outcomes of epidemiological and clinical studies.

TBI severity

The lack of a consensus for grading TBI severity remains problematic for interpreting clinical research and long term outcomes of TBI. Historical grading based on GCS [7] remains the mainstay of severe TBI diagnosis (GCS 3-8), however, there is no consensus on other relevant clinical features such as intracranial haemorrhage or penetrating TBI (together with GCS>8), which potentially should also lead to the diagnosis of severe TBI [8]. Given GCS is a dynamic monitoring tool, we should also consider which GCS to use for severity grading: whether early or delayed; field or arrival; or the best or the worst score [31]. On the other hand, GCS is not sensitive or specific in mild TBI [8], and should no longer be used in isolation to diagnose mild TBI [19,22]. Further, the lack of consensus in the literature regarding GCS 13 as mild or moderate TBI remains a problem [3]. As per ACRM’s position statement, PTA and LOC duration remain key aspects of mild TBI diagnosis [11]. Despite its clinical relevance impacting on the management of TBI, radiological findings and neurological changes are not widely accepted as diagnostic criteria for TBI. Risk of complications in concussion and mild head injury has been examined to identify high risk persons within milder spectrum of TBI [18,19,23].

TBI type

A standardized nomenclature to specify the type of TBI do not exist, but its potential benefits can be anticipated from clinical, research, and knowledge translation perspectives, especially for future targeted therapeutic agents [12]. In the absence of clear guidance for describing TBI, any combination of numerous words to describe the type of TBI are possible – as an example, a person could sustain concussion in football as a result of striking a blunt object (e.g. another person), with diffuse distribution of force, resulting in closed TBI with subdural haematoma. Each of these italicized words contains limited information, and any of these words could reasonably be used in isolation to communicate with other clinicians to describe the type of TBI sustained. A system of clear and mutually exclusive categories and definitions to classify TBI types would be beneficial, especially for clinical research designs [12]. Further, in animal modelling of TBI – especially in designing therapeutic inventions – the type of TBI that is being reproduced by the model should be carefully considered for their relevance and limitations [32].

Regarding concussion, its current definition closely resembles that of TBI, being ‘a brain injury and is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces’ [23]. Concussion as a subset of TBI is predominantly – but not exclusively – used in reference to blunt and low velocity impact resulting in mild injuries in the context of sports [33,34]. However, by definition, concussion could range from no pathological consequences to all severity of TBI [23], and potentially include a wide spectrum of injury mechanisms and pathophysiological processes. For blast-related TBI, the literature has extended beyond mild TBI to include severe TBI of penetrating missile injuries to the brain in military and civilian settings [25], with growing appreciation of extended impact of blastwaves on susceptible organs in close proximity to fluid and air [35]. Therefore, by definition, concussion and blast-related TBI refer to the injury mechanism, respectively, and do not allude to any associated pathoanatomical sequelae of the head trauma.

Treatments in TBI aim to stabilise the medical and rehabilitation issues; prevent secondary complications; restore functional abilities; and provide adaptive equipment to enhance functional independence and social reintegration into the community. The evidence to support psychological interventions (attention training) and cognitive interventions after TBI is strong (Table 3). Cognitive remediative therapies remain the cornerstone of TBI rehabilitation. More evidence, however, is needed for emotional and psychotherapeutic interventions in this population. Although hyperbaric oxygen therapy reduces the risk of death after TBI, there is insufficient evidence that it improves outcomes or quality of life in TBI. Parenteral nutrition is superior to enteral nutrition; and early initiation of nutrition showed reduction in mortality and sepsis in TBI with improved survival and disability outcomes. Interestingly, despite widespread use of physical therapy modalities, the evidence is ‘limited’ for improving balance and gait and ‘insufficient’ to support fitness training in TBI. There is insufficient evidence for acupuncture; hyperventilation; hypothermia therapy; and speech therapy for improving dysarthria in TBI (Table 3). Robust trials in these areas is urgently required to build evidence-based practices in rehabilitation.

Clinical relevance and future directions

The wider community of clinicians treating persons with TBI have much to benefit from a clear and comprehensive diagnostic criterion for TBI according to its severity and type. The present literature is unclear, but alludes to a combination of a etiological, clinical and radiological features to identify the injury sustained. Importantly, GCS, and duration of LOC and PTA, in addition to other clinical and radiological features remain the mainstay for TBI diagnosis. Highly sensitive and emerging diagnostic approaches need clinical correlation for their relevance as a standalone diagnostic marker of TBI. An awareness of various approaches to diagnosing and grading TBI severity should be considered for clinical practice, and should alert clinicians to consider other clinical features suggestive of TBI in for example, isolated skull fractures or small intracranial lesions following head trauma, and guide further management including referrals for rehabilitation assessment and management. For describing the type of TBI, perhaps the most striking aspect of TBI, such as blast-wave exposure in mild TBI; or the findings of a large extradural haemorrhage should be used when communicating with other clinicians.

Limitations

This study has a number of limitations. Firstly, the systematic review was restricted by publication date for recent literature and includes only published data. Secondly, different research methods incorporated in reaching individual recommendations for TBI diagnosis in the included studies have not been weighted in the analysis. Quality assessment was not conducted for studies on diagnosis of TBI and included literature reviews. Thirdly, this review may not be reflective of the clinical pathways and approaches in use in TBI care, which have not been explicitly expressed in the examined literature. The Cochrane register was used for systematic reviews for TBI treatments – individual studies within these reviews were not included.

This systematic review provides an overview of diagnostic criteria and rehabilitation in TBI. Clear diagnostic criteria for TBI could improve TBI care, data collection, and the quality of future clinical trials for specific targeted therapies according to the diagnosis, the severity and the type of TBI. More studies of good methodological design are needed to establish evidence to support interventions used in rehabilitation settings.

We thank Dr. B Amatya for assistance with the NHMRC grading of the Cochrane reviews in TBI.

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