Scott McCullagh

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

Abstract 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.

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.

An open-label study of citalopram for major depression following traumatic brain injury.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti—depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of ≤7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of 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 (R2= 0.098, F = 4.65, p = 0.013). The 5HTTLPR predicted greater occurrence of adverse events (R2= 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.

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 (χ2= 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.

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 ones 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.

An international study of the quality of national-level guidelines on driving with medical illness

BACKGROUND Medical illnesses are associated with a modest increase in crash risk, although many individuals with acute or chronic conditions may remain safe to drive, or pose only temporary risks. Despite the extensive use of national guidelines about driving with medical illness, the quality of these guidelines has not been formally appraised. AIM To systematically evaluate the quality of selected national guidelines about driving with medical illness. DESIGN A literature search of bibliographic databases and Internet resources was conducted to identify the guidelines, each of which was formally appraised. METHODS Eighteen physicians or researchers from Canada, Australia, Ireland, USA and UK appraised nine national guidelines, applying the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS Relative strengths were found in AGREE II scores for the domains of scope and purpose, stakeholder involvement and clarity of presentation. However, all guidelines were given low ratings on rigour of development, applicability and documentation of editorial independence. Overall quality ratings ranged from 2.25 to 5.00 out of 7.00, with modifications recommended for 7 of the guidelines. Intra-class coefficients demonstrated fair to excellent appraiser agreement (0.57-0.79). CONCLUSIONS This study represents the first systematic evaluation of national-level guidelines for determining medical fitness to drive. There is substantive variability in the quality of these guidelines, and rigour of development was a relative weakness. There is a need for rigorous, empirically derived guidance for physicians and licensing authorities when assessing driving in the medically ill.

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.