Activity restriction for short-term and medium-term outcomes following mild traumatic brain injury

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of activity restriction or rest in comparison to no restriction for short-term (one week) and medium-term (one month) outcomes in adults and children who have sustained acute mild traumatic brain injury.

Background

Description of the condition

Traumatic brain injury (TBI) involves an alteration of mental functions following trauma to the head (Vos 2002; Cassidy 2004b). It is estimated that approximately 90% of TBIs are classified as 'mild' using the standard definition of the American Congress of Rehabilitation Medicine published in 1993 (Ruff 2009; Mild 1993). According to this definition, a mild TBI (mTBI) is defined by the presence of a head injury resulting from blunt head trauma and/or deceleration or acceleration forces, a Glasgow coma scale of 13 to 15 and at least one of the four following criteria (Mild 1993):

  1. Any period of observed or self-reported loss of consciousness lasting 30 minutes or less,

  2. Any loss of memory for events immediately before or after the trauma,

  3. Any alteration in mental state at the time of the accident (e.g. feeling dazed, disoriented or confused),

  4. Observed signs of other neurological or neuropsychological dysfunction that may or may not be transitory,

and the absence of the following criteria:

  1. Post-traumatic amnesia greater than 24 hours,

  2. Glasgow Coma Scale score of less than 13, more than 30 minutes following the trauma.

Mild TBI is a common reason for consulting an emergency department. A systematic review of the literature, conducted by the World Health Organisation (WHO), reported approximately 600 cases of mTBI per 100,000 adults in North America (Bazarian 2005; Cassidy 2004a; Cassidy 2004b; Jager 2000; Sosin 1996). This incidence is higher for young adults and athletes showing rates varying between 0.4 cases per 1000 participants-games for football, and 17 cases per 1000 participants-games for ice hockey (Boden 1998; Buckley 1988; Cassidy 2004b; Jorgensen 1986; Powell 1999; Roberts 1999; Tegner 1996). The WHO's reported incidence of mTBI in children varies from 50 to 100 cases per 100,000 children-years depending on age (Cassidy 2004b; Durkin 1998; Rivara 1982; Rivara 1984). A review by the American Academy of Paediatrics (AAP) reported in 2001 that TBI was responsible for 600,000 visits to the emergency department, 95,000 hospitalisations and costs exceeding USD 1 billion per year in the United States of America (Schutzman 2001). Also, TBI was the leading cause of death among children.

There are more than 100 published studies evaluating neurological complications due to mTBI (Carroll 2004; Pertab 2009). These studies report that between 55% and 90% of patients suffering from an mTBI will show variable post-concussion symptoms during the week following the incident (Carroll 2004; King 1996). These symptoms can be of a cognitive (memory loss, attention deficit, etc), somatic (headache, fatigue, nausea) or psychological nature (depression, irritability, etc.). For example, it has been reported that the median duration of headache following an mTBI is one week (Lowdon 1989).

Most studies suggest that the long-term evolution of mTBI is excellent with complete resolution of symptoms within three months (Carroll 2004; King 1996; King 1999). However, some conflicting studies report that 40% of patients suffering mTBI will have persistent symptoms at one month post injury (Ingebrigtsen 1998) and as many as 15% remain symptomatic at one year post injury (Alexander 1995; Reitan 1999).

A paediatric systematic review reported that most children aged younger than 16 with symptoms of mTBI have complete resolution of these symptoms within 2 to 12 weeks (Carroll 2004).  However, children sustaining mTBI are at higher risk of developing attention deficit hyperactivity disorder (McGinn 2000). Also, studies have suggested that mTBI increases the risk of behavioural problems for young children (Anderson 2009; Beauchamp 2011). This is related to recent findings in neuropsychology suggesting that the immature brain of young children is more sensitive to trauma during some critical phase of development (Anderson 2005). There are also important financial consequences of paediatric TBI. For example, mTBI children represent 90% of the hospitalisation days among all children admitted for all levels of TBI (Kraus 1987). 

Description of the intervention

Most patients requiring medical resources secondary to mTBI are initially evaluated at the emergency department. Once proper evaluation is completed, treatments offered for patients suffering from mTBI are driven mainly by the symptoms. These include medications given in the acute phase to decrease pain, nausea or dehydration. There are very few studies evaluating potential treatment for patients with mTBI. A systematic review was conducted by the WHO to evaluate the prevalence, outcomes and potential treatments for mTBI (Borg 2004). Only 16 studies describing potential treatment for mTBI were included and none of these evaluated activity restriction or rest.  More recently, a literature review evaluated return-to-play guidelines for children (Purcell 2009). The main conclusion was the paucity of studies regarding management of concussion among children.

Review articles and guidelines discussing the management of mTBI generally recommend activity restriction (Cushman 2001; McCrory 2009; Standaert 2007; Willer 2006). For example, in 2009 a consensus statement from the 3rd international conference on concussion in sport was published in multiple journals (McCrory 2009). The authors reported "the cornerstone of concussion management is physical and cognitive rest until symptoms resolve". A survey reported in 2001 that 40% of neurologists in Europe recommend full bed rest after mTBI (de Kruijk 2001). However, the recommendation regarding activity restriction lacks a scientific evidence base. This was highlighted by a recent study showing poor rigour in the development of guidelines regarding mTBI (Berrigan 2011). Also, a randomised controlled trial published in 2002 suggested that for adults who have sustained mTBI, full bed rest had no impact on symptom resolution (de Kruijk 2002).

Why it is important to do this review

Among people with TBI, 90% have mTBI. Therefore the financial and societal impact of mTBI is of great consequence. While most people with TBI have an excellent prognosis after three months, many present persistent symptoms at one week following injury (Carroll 2004; King 1996; Lowdon 1989). It is therefore imperative to identify treatment modalities capable of improving short-term and medium-term outcomes for people who have sustained mTBI. 

In September 2011, there were 17 systematic reviews evaluating a treatment for TBI in The Cochrane Library. However, the primary outcomes reported in these studies, such as death or the Glasgow Outcome Scale, are only relevant for severe or moderate TBI. To our knowledge, there is no systematic review of the potential treatments to decrease short-term symptoms for patients with mTBI. Nor is there evaluation of the potential impact of activity restriction or rest for these patients.

Objectives

To assess the effects of activity restriction or rest in comparison to no restriction for short-term (one week) and medium-term (one month) outcomes in adults and children who have sustained acute mild traumatic brain injury.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials. A study will be considered randomised if the day of the head injury, the day of admission to the hospital or the date of birth (day) is the method of randomisation because such injuries occur to patients randomly.

Types of participants

We will include patients of all ages suffering from acute mild TBI. Also, we will include studies evaluating all types of TBI (from mild to severe) but from which patients with mTBI can be analysed separately.

The injury will have to have occurred in the preceding 24 hours. Mild TBI is defined by the presence of a head injury resulting from blunt head trauma or deceleration or acceleration forces, a Glasgow Coma Scale score of 13 to 15 and at least one of the four following criteria (Mild 1993):

  1. Any period of observed or self-reported loss of consciousness lasting 30 minutes or less,

  2. Any loss of memory for events immediately before or after the trauma,

  3. Any alteration in mental state at the time of the accident (e.g. feeling dazed, disoriented or confused),

  4. Observed signs of other neurological or neuropsychological dysfunction that may or may not be transitory,

and the absence of the following criteria:

  1. Post-traumatic amnesia greater than 24 hours,

  2. Glasgow Coma Scale score of less than 13, more than 30 minutes following the trauma.

Types of interventions

The intervention of interest will be activity restriction. This will include: bed rest, restriction of intellectual activity, computer restriction, restriction from school, sport activity restriction, or work restriction. It will also include any studies evaluating programs of 'return-to-play' that involve waiting before the return to play.

Types of outcome measures

Primary outcomes

The primary outcome will be the presence of somatic symptoms (headaches, nausea, sleeping problems) one week and one month following TBI.

Secondary outcomes
  1. Cognitive symptoms (attention deficiency, amnesia, learning problems, etc).

  2. Psychological symptoms (irritability, anxiety, depression).

  3. Social issues (work absenteeism, return to play or to school).

  4. Post concussion syndrome as measured by a validated scale at one week following TBI.

  5. Post concussion syndrome as measured by a validated scale at one month following TBI.

  6. Time to return to play for an athlete.

  7. Time to return to work.

  8. Time to return to school for children.

  9. Number of missed days from school or work.

  10. Cognitive performance using a validated scale for cognitive evaluation at one week and one month.

  11. Health-related quality of life as measured by a validated scale.

  12. Adverse effects.

Search methods for identification of studies

We will not restrict our search by language or publication status.

Electronic searches

We will search the following electronic databases:

  1. Cochrane Injuries Group specialised register (present version);

  2. Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) (latest issue);

  3. MEDLINE (Ovid) (1950 to present);

  4. EMBASE (Ovid) (1980 to present);

  5. CINAHL (EBSCO) (1982 to present);

  6. ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to present);

  7. ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to present).

The MEDLINE search strategy (Appendix 1) will be adapted as necessary for each of the other databases.

Searching other resources

We will search the reference lists of all included studies and previously published reviews for additional material. We will also contact authors and experts in the field to identify additional studies.

We will search the following trial registers and contact the authors of unpublished studies:

We will search for unpublished grey literature by evaluating the following internet resources:  

  • OpenSIGLE.

  • New York Academy of Medicine (Grey Literature Collection).

  • Proquest for theses and dissertations.

 We will handsearch the proceedings of the following conferences for the years 2008 to 2011:

  • Society of Academic Emergency Medicine (USA).

  • Canadian Association of Emergency Physician.

  • American Association of Neurological Surgeon.

  • International Brain Injury Association.

  • International Neuropsychological Society.

Data collection and analysis

We will work with the Cochrane Injuries Group Trials Search Co-ordinator to run the searches. The search results will be collated using bibliographic software such as EndNote and duplicates will be removed before two authors independently carry out the screening process. 

Selection of studies

Two authors (AD, BC, JG and MW) will independently screen titles and abstracts for potential inclusion. The full text of all selected studies will be obtained and two authors (MW and either JG or BC) will select studies using pre-specified inclusion criteria.  All excluded studies will be listed, with reasons for the exclusion. Any differences will be resolved through discussion with a third party. This evaluation will permit the exclusion of studies for which it is impossible to isolate data regarding mTBI from other levels of TBI. 

Data extraction and management

One author (MW) with experience in systematic reviews will extract information on method of randomisation and allocation concealment, blinding of participants, blinding of outcome assessment, incomplete follow up, selective reporting, otehr sources of bias, types of participants, types of interventions, types of outcomes and outcome data. Another co-author (JG) will review data extraction. Data will be extracted using a standardised data extraction form. In case of missing or unclear data, we will contact the corresponding author of the study.

Assessment of risk of bias in included studies

For each included study, two authors (MW and JG) will evaluate methodological quality using the 'Risk of bias' assessment tool in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). They will evaluate risk of bias through assessing: sequence generation, allocation concealment, blinding, incomplete outcome data (assessments will be made for each main outcome or class of outcomes), selective outcome reporting and other sources of bias.

Measures of treatment effect

If possible, we will calculate the risk ratio (RR) and 95% confidence interval (CI) for every categorical outcome measured in two or more studies evaluating the same treatment. For continuous outcomes, we will calculate the mean difference (MD). We will report the 95% CI for each measure of effect. There is a possibility that all the identified studies will not be comparable. If this is the case, we will report a qualitative description of all identified studies.

Dealing with missing data

We will contact study authors to obtain missing information. If the missing data remain unavailable we will discuss the potential impact of the missing data during the interpretation of the results.

Assessment of heterogeneity

We will measure heterogeneity of effect among comparable studies using the I2 statistic (Higgins 2011). Using this, a difference of 25% or higher will be considered heterogeneous. In the absence of heterogeneity, we will use a fixed-effect model of analysis (Greenland 1985) while a random-effects model will be used in case of heterogeneity (DerSimonian 1986).

Assessment of reporting biases

We expect to identify fewer than 10 studies in our systematic review. Therefore, we do not anticipate evaluating publication bias using a funnel plot because the power of the test is too low to distinguish chance from real asymmetry. If more than 10 studies are included in a future version, we will perform funnel plots and a linear regression test (Egger 1997) to examine the likely presence of reporting bias in meta-analysis. A P value less than 0.1 will be considered statistically significant for the linear regression test.

Data synthesis

We will perform a meta-analysis using the Mantel-Haenszel method among comparable studies. We will use Review Manager software for all analyses.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analyses by grouping the type of activity restriction:

  • Full bed rest.

  • Sport activity restriction.

  • Cognitive activity restriction (including computer, television, homework, etc.).

  • School/work restriction.

We will perform subgroup analyses for the following age groups:

  • Preschool children (younger than 5 years old).

  • School-aged children (5 to 12 years old).

  • Teenagers (13 to 17 years old).

  • Adults (18 to 65 years old).

  • Seniors (more than 65 years old).

We will perform subgroup analyses for the following potential confounders:

  • Initial Glasgow scale (13 versus 14 to 15).

  • Presence/absence of a bleeding disorder.

  • Presence/absence of abnormalities on the head CT scan.

  • Past medical history of attention deficit and hyperactivity for children.

  • Past medical history of psychiatric disease.

  • Prior TBI.

  • Presence of a concomitant facial injury.

  • Socioeconomic status.

Sensitivity analysis

If the number of included studies is sufficient (more than five), we will perform a sensitivity analysis on the effect the risk of bias on the outcomes. The following sensitivity analysis is planned a priori. We will examine if the conclusions change after removing studies with high risk of bias, and check for the robustness of the observed findings.

We will perform a sensitivity analysis excluding the studies at moderate or high risk of bias according to the 'Risk of bias' assessment tool in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This analysis will exclude studies with high risk of bias according to their allocation concealment status.

Acknowledgements

The authors thank Dr Francine Ducharme and Dr Caroline Chartrand for internal revision of the protocol.

Appendices

Appendix 1. MEDLINE (OvidSP) Search strategy

1.exp Craniocerebral Trauma/
2.exp Unconsciousness/
3.exp Cerebrovascular Trauma/
4.exp Epilepsy, post traumatic/
5.exp Multiple Trauma/
6.exp Glasgow Coma Scale/
7.exp Glasgow Outcome Scale/
8.(Glasgow adj (coma or outcome) adj (scale* or score*)).ab,ti.
9.6 or 7 or 8
10.(injur* or trauma* or damag* or wound* or fractur* or contusion* or haematoma* or hematoma* or haemorrhag* or hemorrhag* or pressur* or lesion* or destruction* or oedema* or edema* or contusion* or concus*).ti,ab.
11.9 and 10
12.(mild adj5 (head or crani* or cerebr* or capitis or brain* or forebrain* or skull* or hemispher* or intra?cran* or inter?cran* or intracran* or intercran* or multiple) adj3 (injur* or trauma* or damag* or lesion* or wound* or destruction* or oedema* or edema* or contusion* or concus* or fracture*)).ab,ti.
13.(mild adj5 (unconscious* or coma* or concuss*) adj3 (injur* or trauma* or damag* or wound* or fracture* or contusion* or haematoma* or hematoma* or haemorrhag* or hemorrhag* or pressur*)).ti,ab.
14.1 or 2 or 3 or 4 or 5 or 11 or 12 or 13
15.exp emergency service, hospital/
16.exp trauma centers/
17.exp Ambulatory Care Facilities/
18.((emergency or emergencies or urgen* or free?standing or walk?in or trauma* or ambulatory) adj3 (room* or department* or cent* or clinic* or unit* or facilit*)).ab,ti.
19.((accident adj1 emergenc*) or "ER" or "ED").ab,ti.
20.15 or 16 or 17 or 18 or 19
21.14 and 20
22.randomi?ed.ab,ti.
23.randomized controlled trial.pt.
24.controlled clinical trial.pt.
25.placebo.ab.
26.clinical trials as topic.sh.
27.randomly.ab.
28.trial.ti.
29.22 or 23 or 24 or 25 or 26 or 27 or 28
30.(animals not (humans and animals)).sh.
31.29 not 30
32.21 and 31

Contributions of authors

ADA conceived the idea for the review. JG drafted the protocol and it was reviewed by all co-authors.

Declarations of interest

None known.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Quebec Health Research Foundation, Canada.

    Traumatology committee

Ancillary