Cluster-based analysis of PTSD-Checklist for DSM-5 (PCL-5) in civilians with post-concussive cognitive changes.

OBJECTIVE: This study explores the relationship between PTSD symptoms and cognition in patients with persistent post-concussive symptoms (PPCS). METHODS: Adults with PPCS presenting to a specialized brain injury clinic provided demographic and injury information and completed the PTSD checklist for DSM-5, Generalized Anxiety Disorder Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). The Montreal Cognitive Assessment (MoCA) was used to screen for possible cognitive concerns. Multiple regression analysis (MLR) adjusting for age, sex, mechanism of injury, psychiatric history, number of previous concussions, months since most recent injury, and mental health questionnaire scores was used to determine associations between PTSD and cognition. Binomial logistic regression explored the relationship between domains of the MoCA and PCL-5 scores. RESULTS: We found a negative correlation between MoCA scores, PCL-5 (ρ=-0.211, p = 0.009) and PHQ-9 (ρ=-0.187, p = 0.021) in patients with PPCS and collinearity of PCL-5 and PHQ-9 scores. Significantly higher Arousal and Reactivity cluster scores within the PCL-5 were associated with poorer scores on naming and abstract tasks on the MoCA. CONCLUSION: The association between specific PCL-5 clusters and lower MoCA scores may represent a viable target for psychotherapeutic and psychopharmacologic intervention in patients with cognitive changes associated with PPCS.

Unraveling Metabolic Changes following Stroke: Insights from a Urinary Metabolomics Analysis.

The neuropathological sequelae of stroke and subsequent recovery are incompletely understood. Here, we investigated the metabolic dynamics following stroke to advance the understanding of the pathophysiological mechanisms orchestrating stroke recovery. Using a nuclear magnetic resonance (NMR)-driven metabolomic profiling approach for urine samples obtained from a clinical group, the objective of this research was to (1) identify novel biomarkers indicative of severity and recovery following stroke, and (2) uncover the biochemical pathways underlying repair and functional recovery after stroke. Urine samples and clinical stroke assessments were collected during the acute (2-11 days) and chronic phases (6 months) of stroke. Using a 700 MHz 1H NMR spectrometer, metabolomic profiles were acquired followed by a combination of univariate and multivariate statistical analyses, along with biological pathway analysis and clinical correlations. The results revealed changes in phenylalanine, tyrosine, tryptophan, purine, and glycerophospholipid biosynthesis and metabolism during stroke recovery. Pseudouridine was associated with a change in post-stroke motor recovery. Thus, NMR-based metabolomics is able to provide novel insights into post-stroke cellular functions and establish a foundational framework for future investigations to develop targeted therapeutic interventions, advance stroke diagnosis and management, and enhance overall quality of life for individuals with stroke.

Assessment of sleep parameters in adults with persistent post-concussive symptoms.

OBJECTIVES: The primary aim of this study was to characterize sleep in adults with persistent post-concussive symptoms (PPCS). Secondary aims explored relationships between sleep parameters, injury characteristics, and symptom questionnaires. METHODS: This case-controlled, cross-sectional study recruited adults (18-65yrs) diagnosed with PPCS and age and sex-matched controls. Participants wore a wrist-worn actigraph for 3-7 nights and completed daily sleep diaries. Participants completed questionnaires examining daytime sleepiness, fatigue, anxiety/depressive symptoms, and sedentariness. Sleep parameters were compared between groups using Mann-Whitney U tests. Secondary analyses used two-way ANOVA and Spearman's rank correlations. RESULTS: Fifty adults with PPCS (43.7 ± 10.6yrs, 78 % female) and 50 controls (43.6 ± 11.0yrs) were included in this study. Adults with PPCS had significantly longer sleep onset latency (PPCS 16.99 ± 14.51min, Controls 8.87 ± 6.44min, p < 0.001) and total sleep time (PPCS 8.3 ± 1.0hrs, Control 7.6 ± 0.9hrs, p = 0.030) compared to controls, but woke up later (PPCS 7:57:27 ± 1:36:40, Control 7:17:16 ± 0:50:08, p = 0.026) and had poorer sleep efficiency (PPCS 77.9 ± 7.5 %, Control 80.8 ± 6.0 %, p = 0.019) than controls. Adults with PPCS reported more daytime sleepiness (Epworth Sleepiness Scale: PPCS 8.70 ± 4.61, Control 4.28 ± 2.79, p < 0.001) and fatigue (Fatigue Severity Scale: PPCS 56.54 ± 12.92, Control 21.90 ± 10.38, p < 0.001). Injury characteristics did not significantly affect sleep parameters in adults with PPCS. Actigraphy parameters were not significantly correlated to questionnaire measures. CONCLUSION: Several actigraphy sleep parameters were significantly altered in adults with PPCS compared to controls, but did not correlate with sleep questionnaires, suggesting both are useful tools in characterizing sleep in PPCS. Further, this study provides potential treatment targets to improve sleep difficulties in adults with PPCS.

Blood-Derived Metabolic Signatures as Biomarkers of Injury Severity in Traumatic Brain Injury: A Pilot Study.

Metabolomic biomarkers hold promise in aiding the diagnosis and prognostication of traumatic brain injury. In Canada, over 165,000 individuals annually suffer from a traumatic brain injury (TBI), making it one of the most prevalent neurological conditions. In this pilot investigation, we examined blood-derived biomarkers as proxy measures that can provide an objective approach to TBI diagnosis and monitoring. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined whether (1) blood-derived metabolites change during recovery in male participants with mild to severe TBI; (2) biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery; and (3) changes in metabolites correlate to initial injury severity. Eight male participants with mild to severe TBI (with intracranial lesions) provided morning blood samples within 1-4 days and again 6 months post-TBI. Following NMR analysis, the samples were subjected to multivariate statistical and machine learning-based analyses. Statistical modelling displayed metabolic changes during recovery through group separation, and eight significant metabolic pathways were affected by TBI. Metabolic changes were correlated to injury severity. L-alanine (R= -0.63, p < 0.01) displayed a negative relationship with the Glasgow Coma Scale. This study provides pilot data to support the feasibility of using blood-derived metabolites to better understand changes in biochemistry following TBI.

Ultrasound guided platelet rich plasma injections for post-traumatic greater occipital neuralgia following concussion: a pilot randomized controlled trial.

Background: Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can be transient, frequently lasting only 1 month. As a potential alternative, platelet-rich plasma (PRP) injections are an emerging biological treatment with beneficial effects in peripheral nerve disorders. We investigated the feasibility, safety, and effectiveness of a single PRP injection for post-traumatic GON in comparison to saline or steroid/anesthetic injection. Methods: In this pilot randomized, double-blinded, placebo-controlled trial, 32 adults with post-traumatic GON were allocated 1:1:1 to receive a single ultrasound-guided injection of (1) autologous PRP (2) steroid/anesthetic or (3) normal saline. Our primary outcome was feasibility (recruitment, attendance, retention) and safety (adverse events). Exploratory measures included headache intensity and frequency (daily headache diaries) and additional questionnaires (headache impact, and quality of life) assessed at pre-injection, 1 week, 1 month, and 3 months post-injection. Results: We screened 67 individuals, 55% were eligible and 95% of those participated. Over 80% of daily headache diaries were completed with 91% of participants completing the 3-month outcome questionnaires. No serious adverse events were reported. There were no significant differences between groups for headache intensity or frequency. Headache impact on function test-6 scores improved at 3 month in the PRP (ß = -9.7, 95% CI [-15.6, -3.74], p = 0.002) and saline (ß = -6.7 [-12.7, -0.57], p = 0.033) groups but not steroid/anesthetic group (p = 0.135). Conclusion: PRP is a feasible and safe method for treating post-traumatic GON with comparable results to saline and steroid/anaesthetic. Further trials with larger sample sizes are required.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT04051203.

Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion (GET FAB): protocol for a multisite Canadian randomised controlled trial.

INTRODUCTION: Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments. METHODS AND ANALYSIS: We will conduct a multisite randomised controlled trial with three arms. Participants (n=220) will be recruited from concussion clinics and emergency departments in three Canadian provinces and randomly assigned (1:2:2 ratio) to receive enhanced usual care, GET or prescribed aerobic exercise. The outcome assessment will occur remotely 14-18 weeks following baseline assessment, after completing the 12-week treatment phase. The primary outcome will be symptom severity (Rivermead Post-concussion Symptoms Questionnaire). ETHICS AND DISSEMINATION: Informed consent will be obtained from all participants. All study procedures were approved by the local research ethics boards (University of British Columbia Clinical Research Ethics Board, University of Calgary Conjoint Health Research Ethics Board, University Health Network Research Ethics Board-Panel D). Operational approvals were obtained for Vancouver Coastal Health Research Institute and Provincial Health Services Authority. If GET proves effective, we will disseminate the GET treatment manual and present instructional workshops for clinicians. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT05365776.