Dataset Information

Multi-tract multi-symptom relationships in pediatric concussion.

ABSTRACT:

Background

The heterogeneity of white matter damage and symptoms in concussion has been identified as a major obstacle to therapeutic innovation. In contrast, most diffusion MRI (dMRI) studies on concussion have traditionally relied on group-comparison approaches that average out heterogeneity. To leverage, rather than average out, concussion heterogeneity, we combined dMRI and multivariate statistics to characterize multi-tract multi-symptom relationships.

Methods

Using cross-sectional data from 306 previously concussed children aged 9-10 from the Adolescent Brain Cognitive Development Study, we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first representing microstructural complexity, the second representing axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 symptom measures.

Results

Early multi-tract multi-symptom pairs explained the most covariance and represented broad symptom categories, such as a general problems pair, or a pair representing all cognitive symptoms, and implicated more distributed networks of white matter tracts. Further pairs represented more specific symptom combinations, such as a pair representing attention problems exclusively, and were associated with more localized white matter abnormalities. Symptom representation was not systematically related to tract representation across pairs. Sleep problems were implicated across most pairs, but were related to different connections across these pairs. Expression of multi-tract features was not driven by sociodemographic and injury-related variables, as well as by clinical subgroups defined by the presence of ADHD. Analyses performed on a replication dataset showed consistent results.

Conclusions

Using a double-multivariate approach, we identified clinically-informative, cross-demographic multi-tract multi-symptom relationships. These results suggest that rather than clear one-to-one symptom-connectivity disturbances, concussions may be characterized by subtypes of symptom/connectivity relationships. The symptom/connectivity relationships identified in multi-tract multi-symptom pairs were not apparent in single-tract/single-symptom analyses. Future studies aiming to better understand connectivity/symptom relationships should take into account multi-tract multi-symptom heterogeneity.

Funding

Financial support for this work came from a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (G.I.G.), an Ontario Graduate Scholarship (S.S.), a Restracomp Research Fellowship provided by the Hospital for Sick Children (S.S.), an Institutional Research Chair in Neuroinformatics (M.D.), as well as a Natural Sciences and Engineering Research Council CREATE grant (M.D.).

SUBMITTER: Guberman GI

PROVIDER: S-EPMC9132577 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-tract multi-symptom relationships in pediatric concussion.

Guberman Guido I GI Stojanovski Sonja S Nishat Eman E Ptito Alain A Bzdok Danilo D Wheeler Anne L AL Descoteaux Maxime M

eLife 20220517

<h4>Background</h4>The heterogeneity of white matter damage and symptoms in concussion has been identified as a major obstacle to therapeutic innovation. In contrast, most diffusion MRI (dMRI) studies on concussion have traditionally relied on group-comparison approaches that average out heterogeneity. To leverage, rather than average out, concussion heterogeneity, we combined dMRI and multivariate statistics to characterize multi-tract multi-symptom relationships.<h4>Methods</h4>Using cross-sec ...[more]

PMID: 35579325

Similar Datasets

Project description:ImportanceThe natural progression of symptom change and recovery remains poorly defined in children after concussion.ObjectivesTo describe the natural progression of symptom change by age group (5-7, 8-12, and 13-18 years) and sex, as well as to develop centile curves to inform families about children after injury recovery.Design, setting, and participantsPlanned secondary analysis of a prospective multicenter cohort study (Predicting Persistent Postconcussive Problems in Pediatrics). The setting was 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network. Participants were aged 5 to 18 years with acute concussion, enrolled from August 1, 2013, to May 31, 2015, and data analyses were performed between January 2018 and March 2018.ExposuresParticipants had a concussion consistent with the Zurich Consensus Statement on Concussion in Sport diagnostic criteria and 85% completeness of the Postconcussion Symptom Inventory (PCSI) at each time point.Main outcomes and measuresThe primary outcome was symptom change, defined as current rating minus preinjury rating (delta score), at presentation and 1, 2, 4, 8, and 12 weeks after injury, measured using the PCSI. Symptoms were self-rated for ages 8 to 18 years and rated by the child and parent for ages 5 to 7 years. The secondary outcome was recovery, defined as no change in symptoms relative to current preinjury PCSI ratings (delta score = 0). Mixed-effects models incorporated the total score, adjusting for random effects (site and participant variability), fixed-effects indicators (age, sex, time, age by time interaction, and sex by time interaction), and variables associated with recovery. Recovery centile curves by age and sex were computed.ResultsA total of 3063 children (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 60.7% male) completed the primary outcome; 2716 were included in the primary outcome analysis. For the group aged 5 to 7 years, symptom change primarily occurred the first week after injury; by 2 weeks, 75.6% of symptoms had improved (PCSI change between 0 and 2 weeks, -5.3; 95% CI, -5.5 to -5.0). For the groups aged 8 to 12 years and 13 to 18 years, symptom change was prominent the first 2 weeks but flattened between 2 and 4 weeks. By 4 weeks, 83.6% and 86.2% of symptoms, respectively, had improved for the groups aged 8 to 12 years (PCSI change between 0 and 4 weeks, -9.0; 95% CI, -9.6 to -8.4) and 13 to 18 years (PCSI change between 0 and 4 weeks, -28.6; 95% CI, -30.8 to -26.3). Sex by time interaction was significant only for the adolescent group (β = 0.32; 95% CI, 0.21-0.43; P < .001). Most adolescent girls had not recovered by week 12.Conclusions and relevanceSymptom improvement primarily occurs in the first 2 weeks after concussion in children and in the first 4 weeks after concussion in preadolescents and male adolescents. Female adolescents appear to have protracted recovery. The derived recovery curves may be useful for evidence-based anticipatory guidance.

Project description:ImportancePediatric concussion affects millions and results in heterogeneous outcomes and recovery trajectories. Given favorable outcome for most children, it is useful to understand characteristics of positive outcome to promote full recovery in all children.ObjectiveTo document the timeframe of recovery to optimal functioning, defined comprehensively across motor-physical, cognitive, socioemotional, and resilience-support domains, after concussion among children ages 8 to 16 years.Design, setting, and participantsFor this prospective cohort study, children ages 8 to 16.99 years with a concussion or orthopedic injury (OI) were recruited between September 2016 and July 2019 from 5 Pediatric Emergency Research Canada emergency departments and assessed approximately 10 days, 3 months, and 6 months after their injury. Data were analyzed from January 29, 2024, to January 11, 2025.ExposureConcussion.Main outcomes and measuresParticipants completed self-report and direct assessment measures of postconcussive symptoms, physical activity and function, balance, cognitive function, quality of life, resilience, and social support. The main outcome was optimal functioning, which was derived from 11 variables and criteria indicative of absence of impairment and average or above functioning in each domain (overall score, 0-11; higher score indicates better function). A longitudinal, multivariable, cumulative probability ordinal regression model was fitted to examine factors associated with optimal functioning.ResultsA total of 967 children (median [IQR] age, 12.3 [10.5-14.3] years; 562 [58.1%] male) were enrolled, including 633 children with a concussion and 334 children with an OI. The median (IQR) optimal functioning scores for the OI group were 6.0 (4.0-8.0) at 10 days, 7.0 (5.0-9.0) at 3 months, and 7 (5.0-9.0) at 6 months, compared with 4.0 (2.0-6.0) at 10 days, 6.0 (4.0-9.0) at 3 months, and 7.0 (4.0-9.0) at 6 months in the concussion group. The 3 main variables (time, sex, and group) were significantly associated with optimal functioning, as were all 2-way interactions. Time was the strongest factor associated with optimal functioning (Wald χ258 = 485.11; P < .001), followed by group (Wald χ26 = 95.10; P < .001), and sex (Wald χ26 = 23.19; P < .001). At the 10-day follow-up, concussion was associated with lower optimal functioning than OI among females (odds ratio [OR], 0.24 [95% CI, 0.16-0.36]) and males (OR, 0.37 [95% CI, 0.26-0.53]). This difference persisted for females at 3 months (OR, 0.57 [95% CI, 0.35-0.93]) but not for males. Optimal functioning was comparable at 6 months.Conclusions and relevanceIn this prospective cohort study of children with concussion, achieving optimal functioning levels across physical, cognitive, socioemotional, and resilience domains took 3 months or more, especially for girls with concussion. Multiple domains of outcome need to be taken into account when considering full recovery and optimal function after pediatric concussion.

Project description:BackgroundConcussed patients have impaired reaction time (RT) and cognition following injury that may linger and impair driving performance. Limited research has used direct methods to assess driving-RT post-concussion. Our study compared driving RT during simulated scenarios between concussed and control individuals and examined driving-RT's relationship with traditional computerized neurocognitive testing (CNT) domains.MethodsWe employed a cross-sectional study among 14 concussed (15.9 ± 9.8 days post-concussion, mean ± SD) individuals and 14 healthy controls matched for age, sex, and driving experience. Participants completed a driving simulator and CNT (CNS Vital Signs) assessment within 48 h of symptom resolution. A driving-RT composite (ms) was derived from 3 simulated driving scenarios: stoplight (green to yellow), evasion (avoiding approaching vehicle), and pedestrian (person running in front of vehicle). The CNT domains included verbal and visual memory; CNT-RT (simple-, complex-, Stroop-RT individually); simple and complex attention; motor, psychomotor, and processing speed; executive function; and cognitive flexibility. Independent t tests and Hedge d effect sizes assessed driving-RT differences between groups, Pearson correlations (r) examined driving RT and CNT domain relationships among cohorts separately, and p values were controlled for false discovery rate via Benjamini-Hochberg procedures (α = 0.05).ResultsConcussed participants demonstrated slower driving-RT composite scores than controls (mean difference = 292.86 ms; 95% confidence interval (95%CI): 70.18-515.54; p = 0.023; d = 0.992). Evasion-RT (p = 0.054; d = 0.806), pedestrian-RT (p = 0.258; d = 0.312), and stoplight-RT (p = 0.292; d = 0.585) outcomes were not statistically significant after false-discovery rate corrections but demonstrated medium to large effect sizes for concussed deficits. Among concussed individuals, driving-RT outcomes did not significantly correlate with CNT domains (r-range: -0.51 to 0.55; p > 0.05). No correlations existed between driving-RT outcomes and CNT domains among control participants either (r-range: -0.52 to 0.72; p > 0.05).ConclusionSlowed driving-RT composite scores and large effect sizes among concussed individuals when asymptomatic signify lingering impairment and raise driving-safety concerns. Driving-RT and CNT-RT measures correlated moderately but not statistically, which indicates that CNT-RT is not an optimal surrogate for driving RT.

Project description:ObjectiveMotor vehicle collisions generate considerable transmitted forces resulting in traumatic brain injury in children presenting to emergency departments (EDs). To date, no large study has examined post-concussive symptoms in children sustaining concussions in motor vehicle collisions. This study aimed to compare trends in acute post-concussive symptom burden in children with concussion following motor vehicle collisions as compared to other injury mechanisms.MethodsThe study is a secondary analysis of the Predicting Persistent Post-concussive Problems in Pediatrics study, which prospectively recruited a multicenter cohort of 3029 children 5-17 years of age presenting to the ED with concussion from 2013-2015. Post-concussive symptom ratings were obtained at pre-specified time points for 12 weeks post-injury, using the validated Post-Concussion Symptom Inventory (PCSI). Symptom severity and recovery trajectories were measured using delta scores on the PCSI (mean post-injury symptom score minus perceived pre-injury score). A multivariable, longitudinal model evaluated the adjusted effect of mechanism of injury (motor vehicle collisions vs other mechanisms) on mean symptom scores, compared to perceived pre-injury reports, and the temporal change in mean scores over during recovery.ResultsOf 3029 study participants, 56 (1.8%) sustained concussion from motor vehicle collisions. Children sustaining concussion in a motor vehicle collision had lower post-concussive symptom scores upon ED presentation, measured as differences from their perceived pre-injury reports, as compared to other injury mechanisms (-0.36 [95% confidence interval (CI) = -0.58, -0.15]). However, the motor vehicle collisions group showed the smallest decline in symptom burden over 1 month following injury (-0.54 [95% CI = -0.81, -0.27]).ConclusionsChildren sustaining concussions in motor vehicle collisions may have lower initial symptom burdens but slower symptom recovery at 1 month compared to other mechanisms of injury and may represent a distinct population for prognostic counseling in the ED requiring further research.

Project description:ImportanceHeadache is the most common symptom after pediatric concussion.ObjectivesTo examine whether posttraumatic headache phenotype is associated with symptom burden and quality of life 3 months after concussion.Design, setting, and participantsThis was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study, conducted September 2016 to July 2019 at 5 Pediatric Emergency Research Canada (PERC) network emergency departments. Children aged 8.0-16.99 years presenting with acute (<48 hours) concussion or orthopedic injury (OI) were included. Data were analyzed from April to December 2022.ExposurePosttraumatic headache was classified as migraine or nonmigraine headache, or no headache, using modified International Classification of Headache Disorders, 3rd edition, diagnostic criteria based on self-reported symptoms collected within 10 days of injury.Main outcomes and measuresSelf-reported postconcussion symptoms and quality-of-life were measured at 3 months after concussion using the validated Health and Behavior Inventory (HBI) and Pediatric Quality of Life Inventory-Version 4.0 (PedsQL-4.0). An initial multiple imputation approach was used to minimize potential biases due to missing data. Multivariable linear regression evaluated the association between headache phenotype and outcomes compared with the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score and other covariates and confounders. Reliable change analyses examined clinical significance of findings.ResultsOf 967 enrolled children, 928 (median [IQR] age, 12.2 [10.5 to 14.3] years; 383 [41.3%] female) were included in analyses. HBI total score (adjusted) was significantly higher for children with migraine than children without headache (estimated mean difference [EMD], 3.36; 95% CI, 1.13 to 5.60) and children with OI (EMD, 3.10; 95% CI, 0.75 to 6.62), but not children with nonmigraine headache (EMD, 1.93; 95% CI, -0.33 to 4.19). Children with migraine were more likely to report reliable increases in total symptoms (odds ratio [OR], 2.13; 95% CI, 1.02 to 4.45) and somatic symptoms (OR, 2.70; 95% CI, 1.29 to 5.68) than those without headache. PedsQL-4.0 subscale scores were significantly lower for children with migraine than those without headache only for physical functioning (EMD, -4.67; 95% CI, -7.86 to -1.48).Conclusions and relevanceIn this cohort study of children with concussion or OI, those with posttraumatic migraine symptoms after concussion had higher symptom burden and lower quality of life 3 months after injury than those with nonmigraine headache. Children without posttraumatic headache reported the lowest symptom burden and highest quality of life, comparable with children with OI. Further research is warranted to determine effective treatment strategies that consider headache phenotype.

Dataset Information

Multi-tract multi-symptom relationships in pediatric concussion.

Background

Methods

Results

Conclusions

Funding

Publications

Multi-tract multi-symptom relationships in pediatric concussion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets