Risk For Persistent Post-concussion Symptoms Research Articles

Early aerobic exercise among adolescents at moderate/high risk for persistent post-concussion symptoms: A pilot randomized clinical trial

PurposeTo determine the proportion of adolescents at moderate/high risk for Persistent Postconcussion Symptoms (PPCS) who develop PPCS when randomized to early aerobic exercise or standard-of-care and examine exercise volume/intensity between groups. MethodsUsing a randomized clinical trial design, we enrolled patients 10–18 years of age who obtained a “Predicting/Preventing Postconcussive Problems in Pediatrics” (5P) risk score ≥6 and enrolled/tested ≤ one-week post-concussion (mean = 5.5 ± 1.5 days post-concussion). Participants were randomized to “Exercise” (5 days/week, 20 min/day aerobic exercise at individualized intensity [80% HR at exercise test cessation]) or “Standard-of-Care” (no exercise recommendations). They returned for re-testing one-month post-concussion, and we remotely monitored exercise between assessments. ResultsSixteen participants enrolled (intervention: n = 9, 56% female, 14.2 ± 2.1 years; standard-of-care: n = 7, 57% female, 13.6 ± 1.7 years). A smaller proportion of the early aerobic exercise group developed PPCS when compared to the standard-of-care group (44% vs. 86%; relative risk = 0.52; 95% confidence interval = 0.34–1.36; number-needed-to-treat = 2.4). ConclusionWe observed that participants randomized to early aerobic exercise had a lower risk of PPCS compared to standard-of-care. Although not statistically significant, these results suggest early/individualized aerobic exercise among those at moderate/high PPCS risk may be effective at reducing that risk, and early aerobic exercise is not detrimental to recovery outcomes.

Evaluation of Posttraumatic Headache Phenotype and Recovery Time After Youth Concussion

The Four Corners Youth Consortium was created to fill the gap in our understanding of youth concussion. This study is the first analysis of posttraumatic headache (PTH) phenotype and prognosis in this cohort of concussed youth. To describe the characteristics of youth with PTH and determine whether the PTH phenotype is associated with outcome. This cohort study examined outcomes from patients in a multi-institutional registry of traumatic brain injury (TBI) clinics from December 2017 to June 2019. Inclusion criteria included being between ages 5 and 18 years at enrollment and presentation within 8 weeks of a mild TBI. Data were analyzed between February 2019 and January 2021. Mild TBI with standard care. Time to recovery and headache 3 months after injury; measurement device is the Postconcussion Symptom Inventory (PCSI). PTH with migraine phenotype was defined as moderate-severe headache that is new or significantly worse compared with baseline and associated with nausea and/or photophobia and phonophobia. A total of 612 patients with 625 concussions were enrolled, of whom 387 patients with 395 concussions consented to participate in this study. One hundred nine concussions were excluded (concussions, rather than patients, were the unit of analysis), leaving 281 participants with 286 concussions (168 [58.7%] girls; 195 [75.6%] White; 238 [83.2%] aged 13-18 years). At the initial visit, 133 concussions (46.5%) were from patients experiencing PTH with a migraine phenotype, 57 (20%) were from patients experiencing PTH with a nonmigraine phenotype, and 96 (34%) were from patients with no PTH. Patients with any PTH after concussion were more likely to have prolonged recovery than those without PTH (median [interquartile range], 89 [48-165] days vs 44 [26-96] days; log-rank P < .001). Patients with PTH and a migraine phenotype took significantly longer to recover than those with nonmigraine phenotype (median [interquartile range], 95 [54-195] days vs 70 [46-119] days; log-rank P = .01). Within each phenotype, there was no significant difference between sexes in recovery or PTH at 3 months. PTH with a migraine phenotype is associated with persistent symptoms following concussion compared with nonmigraine PTH or no PTH. Given that female sex is associated with higher rates of migraine and migraine PTH, our finding may be one explanation for findings in prior studies that girls are at higher risk for persistent postconcussion symptoms than boys.

Brief Autonomic Assessment in Concussion Clinic

To examine the feasibility and tolerability of administering a brief autonomic assessment via capnometry and pupillometry in an outpatient concussion clinic. Both acute and chronic phases of concussion have been associated with autonomic nervous system (ANS) dysregulation. Few concussion clinics currently employ autonomic assessments, which could enhance diagnostic accuracy and treatment recommendations. Although less-studied in outpatient concussion clinics, pupillometry and capnometry are two well-validated, peripheral autonomic assessment approaches that together provide information about both sympathetic and parasympathetic responses. In addition to being objective measures, they are fast and non-invasive. In order to investigate the potential utility of these measures as an addition to clinic procedures, the present study sought to examine their feasibility and tolerability as an adjunctive assessment in clinic. This project employed a prospective, observational research design. Eight patients (ages 20-65, 4 females) diagnosed with concussion (>1 month post injury) underwent a 2-minute baseline capnometry that measured end-tidal CO2, respiration rate, pulse rate, and oxygen saturation. Their pupillary response to light was captured using a pupillometer. Tolerability and feasibility were measured via the following metrics: patient tolerability and comfort Likert scales and administration details (e.g., total duration, logistical difficulties, clinic flow variables). Average rating of comfort for the capnometer and pupillometer were between comfortable (4) to very comfortable (5) on a 5-point Likert scale. There were no difficulties due to participant discomfort or time limitations among all patients, and minimal issues with administration logistics were noted. Both measures were completed for all participants in <5 minutes. Capnometry and pupillometry were found to be both tolerable among patients and feasible to administer in a concussion clinic. Given the ease of administration, further studies should investigate the utility of these portable devices in concussion clinics to objectively identify those at risk for persistent post-concussion symptoms and for early treatment stratification.

Saliva microRNA Biomarkers of Cumulative Concussion.

Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects.

Identifying Persistent Postconcussion Symptom Risk in a Pediatric Sports Medicine Clinic

Background: Although most children report symptom resolution within a month of a concussion, some patients experience persistent postconcussion symptoms (PPCS) that continues for more than 1 month. Identifying patients at risk for PPCS soon after an injury can provide useful clinical information. Purpose: To determine if the Predicting Persistent Post-concussive Problems in Pediatrics (5P) clinical risk score, an emergency department (ED)–derived and validated tool, is associated with developing PPCS when obtained in a primary care sports concussion setting. Study Design: Cohort study; Level of evidence, 3. Methods: We conducted a study of patients seen at a pediatric sports medicine concussion clinic between May 1, 2013, and October 1, 2017, who were <19 years of age and evaluated within 10 days of a concussion. The main outcome was PPCS, defined as symptoms lasting >28 days. Nine variables were used to calculate the 5P clinical risk score, and we assessed the association between the 5P clinical risk score and PPCS occurrence. The secondary outcome was total symptom duration. Results: We examined data from 230 children (mean age, 14.8 ± 2.5 years; 50% female; mean time from injury to clinical assessment, 5.6 ± 2.7 days). In univariable analyses, a greater proportion of those who developed PPCS reported feeling slowed down (72% vs 44%, respectively; P < .001), headache (94% vs 72%, respectively; P < .001), sensitivity to noise (71% vs 43%, respectively; P < .001), and fatigue (82% vs 51%, respectively; P < .001) and committed ≥4 errors in tandem stance (33% vs 7%, respectively; P < .001) than those who did not. Higher 5P clinical risk scores were associated with increased odds of developing PPCS (adjusted odds ratio [OR], 1.62 [95% CI, 1.30-2.02]) and longer symptom resolution times (β = 8.40 [95% CI, 3.25-13.50]). Among the individual participants who received a high 5P clinical risk score (9-12), the majority (82%) went on to experience PPCS. The area under the curve for the 5P clinical risk score was 0.75 (95% CI, 0.66-0.84). After adjusting for the effect of covariates, fatigue (adjusted OR, 2.93) and ≥4 errors in tandem stance (adjusted OR, 7.40) were independently associated with PPCS. Conclusion: Our findings extend the potential use for an ED-derived clinical risk score for predicting the PPCS risk into the sports concussion clinic setting. While not all 9 predictor variables of the 5P clinical risk score were independently associated with the PPCS risk in univariable or multivariable analyses, the combination of factors used to calculate the 5P clinical risk score was significantly associated with the odds of developing PPCS. Thus, obtaining clinically pragmatic risk scores soon after a concussion may be useful for early treatments or interventions to mitigate the PPCS risk.

Clinical Risk Score for Persistent Postconcussion Symptoms Among Children With Acute Concussion in the ED.

Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-<18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.

Predicting mild traumatic brain injury patients at risk of persistent symptoms in the Emergency Department

Objective: To identify factors that can predict which emergency department (ED) patients with mTBI are likely to develop persistent post-concussion symptoms (PPCS).Design: A matched case-control study was conducted at a Level 1 trauma centre between June 2006 and July 2009. Patients diagnosed with mTBI in the ED and diagnosed at a concussion management programme with at least one PPCS (85 cases) were compared to patients diagnosed with mTBI in the ED (340 controls) to determine if factors assessed at the time of ED presentation could predict patients likely to develop persistent symptoms.Results: Multivariable hierarchical logistic regression with variables indicating increased risk for PPCS (prior mTBI, history of depression, history of anxiety, multiple injury, forgetfulness/poor memory, noise sensitivity, or light sensitivity) resulted in a final predictive model including prior mTBI, history of anxiety, forgetfulness/poor memory and light sensitivity. The final model had a specificity of 87.9% and a sensitivity of 69.9%.Conclusions: A strong prediction model to identify those ED patients with mTBI at risk for PPCS was developed and could be easily implemented in the ED; therefore, helping to target those patients who would potentially benefit from close follow-up.