Updated clinical practice guidelines for concussion/mild traumatic brain injury and persistent symptoms.

OBJECTIVE: To introduce a set of revised guidelines for the management of mild traumatic brain injury (mTBI) and persistent symptoms following concussive injuries. QUALITY OF EVIDENCE: The Guidelines for Mild Traumatic Brain Injury and Persistent Symptoms were made available in March 2011 based on literature and information up to 2008. A search for new clinical practice guidelines addressing mTBI and a systematic review of the literature evaluating treatment of persistent symptoms was conducted. Healthcare professionals representing a range of disciplines from Canada and abroad attended a consensus conference to revise the original guidelines in light of new evidence. MAIN MESSAGE: A modified Delphi process was used to create 96 recommendations addressing the diagnosis and management of mTBI and persistent symptoms, including post-traumatic headache, sleep disturbances, mental health disorders, cognitive difficulties, vestibular and vision dysfunction, fatigue and return to activity/work/school. Numerous resources, tools and treatment algorithms were also included to aid implementation of the recommendations. CONCLUSION: The revised clinical practice guideline reflects the most current evidence and is recommended for use by clinicians who provide care to people who experience PPCS following mTBI.

Predicting Posttraumatic Stress Symptoms Following Mild, Moderate, and Severe Traumatic Brain Injury: The Role of Posttraumatic Amnesia.

OBJECTIVE: To explore the relation between posttraumatic amnesia (PTA) and posttraumatic stress symptoms in traumatic brain injury. DESIGN: Single-site prospective cohort study. PARTICIPANTS: A total of 1114 individuals between the ages of 18 and 65 years with a traumatic brain injury seen on average 3 months following injury. Participants were divided into 4 groups according to their duration of PTA: less than 1 hour; 1 to 24 hours; 24 hours to 1 week; and more than 1 week. MAIN MEASURES: Glasgow Coma Scale, PTA, computed tomographic brain scan abnormalities, Impact of Event Scale, the 28-item General Health Questionnaire, and Rivermead Postconcussion Disorder Questionnaire. RESULTS: The duration of PTA less than 1 hour was associated with more avoidant (P < .01) and intrusive (P < .001) posttraumatic stress symptoms and more anxiety according to the General Health Questionnaire (P < .01) than other groups. Regression analysis identified PTA and 3 concussive symptoms (light sensitivity, noise intolerance, and difficulties concentrating) as independent predictors of intrusive posttraumatic stress symptoms. CONCLUSION: Our data, representative of the full range of traumatic brain injury severity, indicate that a brief duration of PTA is a significant risk factor for the development of posttraumatic stress disorder symptoms. The persistence of certain symptoms of postconcussion disorder adds to the risk by possibly acting as a trigger for reminders of the traumatic event.

Clinical practice guidelines for mild traumatic brain injury and persistent symptoms.

OBJECTIVE: To outline new guidelines for the management of mild traumatic brain injury (MTBI) and persistent postconcussive symptoms (PPCS) in order to provide information and direction to physicians managing patients' recovery from MTBI. QUALITY OF EVIDENCE: A search for existing clinical practice guidelines addressing MTBI and a systematic review of the literature evaluating treatment of PPCS were conducted. Because little guidance on the management of PPCS was found within the traumatic brain injury field, a second search was completed for clinical practice guidelines and systematic reviews that addressed management of these common symptoms in the general population. Health care professionals representing a range of disciplines from across Canada and abroad were brought together at an expert consensus conference to review the existing guidelines and evidence and to attempt to develop a comprehensive guideline for the management of MTBI and PPCS. MAIN MESSAGE: A modified Delphi process was used to create 71 recommendations that address the diagnosis and management of MTBI and PPCS. In addition, numerous resources and tools were included in the guideline to aid in the implementation of the recommendations. CONCLUSION: A clinical practice guideline was developed to aid health care professionals in implementing evidencebased, best-practice care for the challenging population of individuals who experience PPCS following MTBI.

Quality of clinical practice guidelines for persons who have sustained mild traumatic brain injury.

BACKGROUND: Mild TBI is one of the most common neurological disorders occurring today. For individuals who experience persistent symptoms following mild TBI, consequences can include functional disability, stress and time away from one's occupation. The objective of the study was to evaluate the quality of clinical practice guidelines (CPGs) that include recommendations on the care of persons who have sustained mild TBI and associated persistent symptoms. METHODS: A minimum of four appraisers used the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument to evaluate seven CPGs found via a systematic search of bibliographic databases and internet resources. RESULTS: High AGREE scores were obtained for the domains Scope and Purpose and Clarity and Presentation. The CPGs fared less well on Rigour of Development, Stakeholder Involvement, Editorial Independence and Applicability. The number of recommendations addressing the care of persistent symptoms following mild TBI was meager, with the exception of military guidelines. CONCLUSIONS: There is considerable variability in the quality of guidelines addressing mild TBI and, overall, the CPGs reviewed score lower on Rigour of Development than CPGs for other medical conditions. There is a clear need for clinical guidance on the management of individuals who experience persistent symptoms following mild TBI.

Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury.

OBJECTIVES: To determine which serotonergic system-related single nucleotide polymorphisms (SNPs) predicted variation in treatment response to citalopram in depression following a traumatic brain injury (TBI). METHODS: Ninety (50 M/40 F, aged 39.9, SD = 18.0 years) post-TBI patients with a major depressive episode (MDE) were recruited into a 6-week open-label study of citalopram (20 mg/day). Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value < 0.025). RESULTS: MTHFR and BDNF SNPs predicted greater treatment response (R(2)= 0.098, F = 4.65, p = 0.013). The 5HTTLPR predicted greater occurrence of adverse events (R(2)= 0.069, F = 5.72, p = 0.020). CONCLUSION: Results suggest that polymorphisms in genes related to the serotonergic system may help predict short-term response to citalopram and tolerability to the medication in patients with MDE following a TBI.

A randomized controlled trial of antidepressant continuation for major depression following traumatic brain injury.

OBJECTIVE: This study examines whether continuation therapy with citalopram can prevent a relapse following remission of major depression due to traumatic brain injury. METHOD: After 65 subjects with DSM-IV-diagnosed major depression following traumatic brain injury were treated with open-label citalopram (20 mg to 50 mg/d), 25 subjects (38.5%) met criteria for remission. Of those, 21 (84.0%) were randomly assigned to either same-dose citalopram or placebo and followed monthly over 40 weeks. Remission was defined as a Hamilton Depression Rating Scale (HDRS) score of ≤ 7 or a Clinical Global Impressions-Improvement rating of "much improved" or better. The main outcome variable was the presence of relapse, as defined by meeting criteria for major depressive episode according to the DSM-IV and an HDRS score ≥ 16. Data were collected from February 16, 2005, to May 5, 2008. RESULTS: Ten subjects were randomly assigned to citalopram and 11 to placebo. There were 3 dropouts, including 1 for adverse drug effects (diarrhea). Relapse occurred in 11 subjects (52.4%), with a mean ± SD time to relapse of 23.52 ± 16.6 weeks. The groups did not differ in relapse rates (drug: 50.0% [5/10] vs placebo: 54.5% [6/11], Fisher exact test, P = .835) or time to relapse (log rank test χ² = 0.148, P = .700). CONCLUSIONS: The present study suggests important limitations of continuation pharmacotherapy in the prevention of relapse of major depression following traumatic brain injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00162916.

Factor analysis of the Rivermead Post-Concussion Symptoms Questionnaire in mild-to-moderate traumatic brain injury patients.

Posttraumatic brain injury patients with depressive symptoms were compared with nondepressed mild and moderate traumatic brain injury (TBI) patients based on their scores on the Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ). A factor analysis demonstrated that the items of the RPCSQ loaded into three factors: mood and cognition, general somatic, and visual somatic symptom groups. Factor scores based on this model were calculated for each group and it was found that depressed subjects reported a greater severity of all three symptom groups compared to nondepressed patients. These results suggest that depression post-TBI may influence patient perception of postconcussion symptoms.

The serotonin transporter polymorphisms and major depression following traumatic brain injury.

OBJECTIVE: The purpose of this study was to examine the role of the serotonin transporter gene polymorphisms on the risk of major depression following traumatic brain injury (TBI). METHODS: Seventy-five patients who had sustained a TBI and who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for mood disorder due to TBI were compared to 99 controls with TBI but no mood disorder. The severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) for the depressed patients. All patients were genotyped for the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with the assay for the rs25531 allelic variant. RESULTS: The distribution of genotype frequencies was not different between the depressed and control groups (chi(2) = 1.43, df = 2, p = 0.488) and for the depressed patients there was no association between HAMD scores and the polymorphisms (t-test = 1.71, df = 68, p = 0.092). CONCLUSION: There was no evidence of association between the serotonin transporter gene polymorphisms and depression post-TBI. Future research is indicated into the possible role of other candidate genes as risk factors for depression in this population.

Randomized treatment trial in mild traumatic brain injury.

OBJECTIVE: To determine whether multidisciplinary treatment of mild traumatic brain injury (MTBI) improves neurobehavioral outcome at 6 months postinjury. METHODS: Subjects with MTBI were randomly assigned to treatment (n=97) or nontreatment (control, n=94) groups. Treated patients were assessed within 1 week of injury and thereafter managed by a multidisciplinary team according to clinical need for a further 6 months. Control subjects were not offered treatment. Six-month outcome measures included: severity of postconcussive symptoms (Rivermead Post-Concussion Disorder Questionnaire), psychosocial functioning (Rivermead Follow-up Questionnaire), psychological distress (General Health Questionnaire), and cognition (neurocognitive battery). RESULTS: Treatment and control subjects were well-matched for demographic and MTBI severity data. In addition, the two groups did not differ on any outcome measure. However, in individuals with preinjury psychiatric difficulties (22.9% of the entire sample), subjects in the treatment group had significantly fewer depressive symptoms 6 months postinjury compared with untreated controls (P=.01). CONCLUSIONS: These findings suggest that routine treatment of all MTBI patients offers little benefit; rather, targeting individuals with preinjury psychiatric problems may prove a more rational and cost-effective approach.

Cognitive impairment associated with major depression following mild and moderate traumatic brain injury.

Traumatic brain injury (TBI) and major depression are neuropsychiatric conditions that have been associated with cognitive dysfunction. The aim of this study was to explore the relationship between major depression and cognitive impairment following mild and moderate TBI. Seventy-four TBI patients were assessed for the presence of major depression using the Structured Clinical Interview for the DSM-IV and completed a neurocognitive assessment battery. Subjects with major depression (28.4%), compared to those without, were found to have significantly lower scores on measures of working memory, processing speed, verbal memory and executive function. Potential mechanisms and implications for treatment are discussed.

Age and major depression after mild traumatic brain injury.

OBJECTIVE: The authors investigated the relationship between age and major depression in the acute period following mild traumatic brain injury (TBI). METHODS: Patients with mild TBI (N=210) were assessed for the presence of major depression with the Structured Clinical Interview for DSM-IV. RESULTS: Older patients (age 60-plus) had lower rates of major depression than younger patients. CONCLUSION: Older patients seem to be relatively resilient to major depression shortly after mild TBI.

The clinical significance of major depression following mild traumatic brain injury.

OBJECTIVE: The authors assessed the association of major depression with behavioral outcome following mild traumatic brain injury. METHOD: Consecutive patients with mild traumatic brain injury (N=170) were assessed for major depression. Those with major depression were compared with those without on self-report measures of psychosocial dysfunction, psychological distress, and postconcussive symptoms in addition to examiner-rated neurobehavioral disturbance. RESULTS: Major depression was seen in 15.3% (N=26) of the subjects after traumatic brain injury, and these individuals showed subjective and objective evidence of poorer outcome. CONCLUSIONS: Major depression is associated with poor outcome across multiple domains. This study highlights the need for the early diagnosis and prompt treatment of major depression following mild traumatic brain injury.

Posttraumatic amnesia and recall of a traumatic event following traumatic brain injury.

The relationship between posttraumatic amnesia (PTA) and symptoms of posttraumatic stress disorder (PTSD) was examined in 282 outpatients at a mean of 53 days after traumatic brain injury (TBI). Patients were assessed for TBI severity, intrusive and avoidant PTSD-type symptoms, and psychological distress, and were stratified into four comparison groups by duration of PTA. Levels of PTSD-type symptoms and psychological distress did not differ significantly between groups. Even patients with PTA >1 week reported intrusive and avoidant PTSD-type symptoms. However, when patients were stratified into those with PTA of <1 hour or >1 hour, the former were more likely to report such symptoms. TBI patients with brief PTA are more likely to experience PTSD-type reactions, but severe TBI with prolonged PTA is not incompatible with such reactions in a subset of patients. Possible mechanisms that could account for this finding are discussed.