Derivation and Initial Validation of Clinical Phenotypes of Children Presenting with Concussion Acutely in the Emergency Department: Latent Class Analysis of a Multi-Center, Prospective Cohort, Observational Study

Yeates, Keith Owen; Tang, Kenneth; Barrowman, Nick; Freedman, Stephen B.; Gravel, Jocelyn; Gagnon, Isabelle; Sangha, Gurinder; Boutis, Kathy; Beer, Darcy; Craig, William; Burns, Emma; Farion, Ken; Mikrogianakis, Angelo; Barlow, Karen M.; Dubrovsky, Alexander Sasha; Meeuwisse, Willem; Gioia, Gérard A.; Meehan, William P.; Beauchamp, Miriam H.; Kamil, Yael; Grool, Anne M.; Hoshizaki, Blaine; Anderson, Peter; Brooks, Brian L.; Vassilyadi, Michael; Klassen, Terry P.; Keightley, Michelle; Richer, Lawrence; DeMatteo, Carol; Osmond, Martin H.; Zemek, Roger

doi:10.1089/neu.2018.6009

Cited by 18 publications

(14 citation statements)

References 33 publications

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“…Few recent studies have parsed heterogeneity in concussion symptoms using clustering analyses. 10-12 The reported subgroups differed from those found in the present study. Differences between symptom profiles arose because our multi-symptom features are associated with brain structure and not driven by variability in symptoms alone.…”

Section: Discussioncontrasting

confidence: 99%

“…To remedy this shortcoming, a growing number of studies aimed to parse the clinical heterogeneity in concussions by algorithmically partitioning patients into discrete subgroups based on symptoms. 10-12 Other studies aim instead to account for heterogeneity in white matter structure alterations. 13-15 Ware et al 15 built individualized maps of white matter abnormalities which revealed substantial inter-subject variability in traumatic axonal injury and minimal consistency of subject-level effects.…”

Section: Introductionmentioning

confidence: 99%

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Multi-tract multi-symptom relationships in pediatric concussion

Stojanovski

Nishat

et al. 2021

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The heterogeneity of white matter damage and symptoms in concussions has been identified as a major obstacle to therapeutic innovation. In contrast, the vast majority of diffusion MRI studies on concussion have traditionally employed group-comparison approaches. Such studies do not consider heterogeneity of damage and symptoms in concussion. To parse concussion heterogeneity, the present study combines diffusion MRI (dMRI) and multivariate statistics to investigate multi-tract multi-symptom relationships. Using dMRI data from a sample of 306 children ages 9 and 10 with a history of concussion from the Adolescent Brain Cognitive Development Study (ABCD study), we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first capturing a mixture of patterns suggestive of microstructural complexity, the second representing almost exclusively axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 behavioural measures that capture well-known symptoms of concussions. We found idiosyncratic symptom-specific multi-tract connectivity features, which would not be captured in traditional univariate analyses. Multivariable connectome-symptom correspondences were stronger than all single-tract/single-symptom associations. Multi-tract connectivity features were also expressed equally across different sociodemographic strata and their expression was not accounted for by injury-related variables. In a replication dataset, the expression of multi-tract connectivity features predicted adverse psychiatric outcomes after accounting for other psychopathology-related variables. By defining cross-demographic multi-tract multi-symptom relationships to parse concussion heterogeneity, the present study can pave the way for the development of improved stratification strategies that may contribute to the success of future clinical trials and the improvement of concussion management.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multi-tract multi-symptom relationships in pediatric concussion

Stojanovski

Nishat

et al. 2021

Preprint

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“…Around 12% of children sustaining a mTBI have PPCS three months following injury 5 . There are several PPCS phenotypes with the commonest symptoms being headaches, fatigue, sleep disturbances and cognitive difficulties 6 . These symptoms have a detrimental impact on health-related quality of life and long-term outcomes [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Default mode network anatomy and function is linked to pediatric concussion recovery

Iyer

Zalesky

Barlow

et al. 2019

Preprint

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Objective:To determine whether anatomical and functional brain features relate to key persistent post-concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS.Methods: 110 children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children's Hospital. The primary outcome was the Post-Concussion Symptom Inventory (PCSI, parent proxy). Sleep disturbance scores (PCSI sub-domain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks post-injury and 8-10 weeks post-injury. Grey matter volumes were assessed using magnetic resonance imaging (MRI) and voxel-based morphometry. Functional connectivity was estimated using resting-state MRI. Two complementary machine learning methods were used to assess if the combination of grey matter and functional connectivity indices carried meaningful prognostic information.Results: Higher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in grey matter volume and local functional connectivity in two key nodes of the default mode network: the posterior cingulate cortex and the medial prefrontal cortex. Sleep-related disturbances also significantly correlated with reductions in functional connectivity between these brain regions. The combination of structural and functional brain indices associated to individual variations in the default mode network accurately predicted clinical outcomes at follow-up (area under the curve = 0.86). Interpretation:These results highlight that the function-structure profile of core default mode regions underpins sleep-related problems following mTBI and carries meaningful prognostic information for pediatric concussion recovery.

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“…Historically, psychometric analyses of various symptom scales identified four subdomains of concussion symptoms: physical, cognitive, emotional and sleep/fatigue [9][10][11]. Recent studies support that mTBIs are heterogeneous in clinical presentation across domains, resulting in thematic phenotypes that allow for subtype-targeted management [12][13][14][15][16]. A US Department of Defense-tasked expert workgroup classified postconcussive symptoms and defined nonmutually exclusive clinically relevant subtypes including: vestibular; ocular-motor; anxiety/mood; cognitive; and headache/migraine [15,17,18].…”

mentioning

confidence: 99%

Representation of concussion subtypes in common postconcussion symptom-rating scales

et al. 2019

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Aim: Postconcussion symptom-rating scales are frequently used concussion assessment tools that do not align directly with new expert, consensus-based concussion subtype classification systems. This may result in delays in concussion diagnosis, subspecialty referral and rehabilitative strategies. Objective: To determine the representation of subtype-directed symptomatology in common postconcussion symptom-rating scales. Methods: Literature review and expert consensus were used to compile commonly used concussion symptom-rating scales. Statistics were generated to describe the degree of representation of the consensus symptom set. Results: The percentage of symptoms representing each subtype/associated condition is low overall (15–26%). The ocular-motor (11%) and vestibular subtypes (19%) and cervical strain (5%)-associated condition were the most under-represented and also had the greatest unmet needs. Conclusion: Concussion subtypes do not have equal representation on commonly used concussion symptom-rating scales. There is a need for a subtype-directed symptom assessment to allow for increased accuracy of diagnosis and to guide management.

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Derivation and Initial Validation of Clinical Phenotypes of Children Presenting with Concussion Acutely in the Emergency Department: Latent Class Analysis of a Multi-Center, Prospective Cohort, Observational Study

Cited by 18 publications

References 33 publications

Multi-tract multi-symptom relationships in pediatric concussion

Multi-tract multi-symptom relationships in pediatric concussion

Default mode network anatomy and function is linked to pediatric concussion recovery

Representation of concussion subtypes in common postconcussion symptom-rating scales

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