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OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion. METHODS: This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts. RESULTS: Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3). CONCLUSIONS: Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

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OBJECTIVE: To identify differential trajectories of neurocognitive outcomes following pediatric concussion and investigate predictors associated with patterns of recovery up to 3 months. METHODS: 74 participants aged 8-17 years completed attention/working memory, processing speed, and executive function measures at 2 weeks, 1 month, and 3 months post-injury. We used principal component analysis to generate a composite of information processing. Group-based trajectory modeling identified latent trajectories. Multinominal logistic regression was used to examine associations between risk factors and trajectory groups. RESULTS: We identified three trajectories of neurocognitive outcomes. The medium (54.6%) and high improving groups (35.8%) showed ongoing increase in information processing, while the low persistent group showed limited change 3 months post-injury. This group recorded below average scores on Digit Span Forward and Backward at 3 months. History of pre-injury headache was significantly associated with the persistent low scoring group, relative to the medium improving (p = 0.03) but not the high improving group (p = 0.09). CONCLUSIONS: This study indicates variability in neurocognitive outcomes according to three differential trajectories, with groups partially distinguished by preexisting child factors (history of frequent headaches). Modelling that accounts for heterogeneity in individual outcomes is essential to identify clinically meaningful indices that are indicative of children requiring intervention.

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OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury. METHODS: Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion. Participants were followed up at 2 weeks postinjury to determine PTH status. PTH was defined per clinical guidelines as a new or worsened headache compared with preinjury. An untargeted proteomics analysis using data-independent acquisition (DIA) was performed. Principal component analysis and hierarchical clustering were used to reduce the dimensionality of the protein dataset. RESULTS: A total of 907 proteins were reproducibly identified from 82 children within 48 hours of concussion. The mean participant age was 12.78 years (SD 2.54 years, range 8-17 years); 70% of patients were male. Eighty percent met criteria for acute PTH in the ED, while one-third of participants with follow-up experienced PTH at 2 weeks postinjury (range 8-16 days). Hemoglobin subunit zeta (HBZ), cystatin B (CSTB), beta-ala-his dipeptidase (CNDP1), hemoglobin subunit gamma-1 (HBG1), and zyxin (ZYX) were weakly associated with PTH at 2 weeks postinjury based on up to a 7% increase in the PTH group despite nonsignificant Benjamini-Hochberg adjusted p values. CONCLUSIONS: This discovery study determined that no capillary blood protein markers, measured at ED presentation within 48 hours of concussion, can predict children at risk of persisting PTH at 2 weeks postinjury. While HBZ, CSTB, CNDP1, HBG1, and ZYX were weakly associated with PTH at 2 weeks postinjury, there was no specific blood protein signature predictor of PTH in children after concussion. There is an urgent need to discover new blood biomarkers associated with PTH to facilitate risk stratification and improve clinical management of pediatric concussion.

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OBJECTIVE: Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion. METHODS: 240 children and adolescents aged 5-18 years (M=11.64, SD=3.16) completed assessments from time of injury to 3 months postinjury. Separate linear mixed effects models were conducted for child and parent ratings on the PedsQL-Multidimensional Fatigue Scale to plot recovery across domains (General, Cognitive, Sleep/Rest) and Total fatigue, from 1 week to 3 months postinjury. Two-block hierarchical regression analyses were then conducted for parent and child ratings of fatigue at each time point, with age, sex and acute symptoms in block 1 and child and parent mental health variables added to block 2. RESULTS: There was a significant reduction in both child and parent ratings across the 3 months postinjury for all fatigue domains (all p<0.001). For both child and parent fatigue ratings, child mental health was the most significant factor associated with fatigue at all time points. Adding child and parent mental health variables in the second block of the regression substantially increased the variance explained for both child and parent ratings of fatigue. CONCLUSION: Our findings confirm that fatigue improves during the first 3 months postconcussion and highlights the importance of considering child and parent mental health screening when assessing patients with persisting postconcussive symptoms.

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OBJECTIVE: Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. METHODS: As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. RESULTS: Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. CONCLUSIONS: Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

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The Sports Concussion Assessment Tool-5th Edition (SCAT5) and the child version (Child SCAT5) are the current editions of the SCAT and have updated the memory testing component from previous editions. This study aimed to validate this new memory component against the Rey Auditory Verbal Learning Test (RAVLT) as the validated standard. This prospective, observational study, carried out within The Royal Children's Hospital Emergency Department, Melbourne, Australia, recruited 198 participants: 91 with concussion and 107 upper limb injury or healthy sibling controls. Partial Pearson correlations showed that memory acquisition and recall on delay aspects of the SCAT5 were significantly correlated with the RAVLT equivalents when controlling for age (p < 0.001, r = 0.565 and p < 0.001, r = 0.341, respectively). Factor analysis showed that all RAVLT and SCAT5 memory components load on to the same factor, accounting for 59.13% of variance. Logistic regression models for both the RAVLT and SCAT5, however, did not predict group membership (p > 0.05). Receiver operating curve analysis found that the area under the curve for all variables and models was below the recommended 0.7 threshold. This study demonstrated that the SCAT5 and Child SCAT5 memory paradigm is a valid measure of memory in concussed children.

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The Sport Concussion Assessment Tool 5th Edition (SCAT5) is a standardized measure of concussion. In this prospective observational study, the ability of the SCAT5 and ChildSCAT5 to differentiate between children with and without a concussion was examined. Concussed children (n=91) and controls (n=106) were recruited from an emergency department in three equal-sized age bands (5-8/9-12/13-16 years). Analysis of covariance models (adjusting for participant age) were used to analyze group differences on components of the SCAT5. On the SCAT5 and ChildSCAT5, respectively, youth with concussion reported a greater number (d=1.47; d=0.52) and severity (d=1.27; d=0.72) of symptoms than controls (all p<0.001). ChildSCAT5 parent-rated number (d=0.98) and severity (d=1.04) of symptoms were greater for the concussion group (all p<0.001). Acceptable levels of between-group discrimination were identified for SCAT5 symptom number (AUC=0.86) and severity (AUC=0.84) and ChildSCAT5 parent-rated symptom number (AUC=0.76) and severity (AUC=0.78). Our findings support the utility of the SCAT5 and ChildSCAT5 to accurately distinguish between children with and without a concussion.

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It is often argued that successive editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) have relaxed diagnostic criteria and thereby inflated rates of diagnosis. This claim has yet to be examined systematically. We quantitatively reviewed 123 studies in which one sample was concurrently diagnosed using two consecutive DSM editions (i.e., DSM-III & DSM-III-R, DSM-III-R & DSM-IV, or DSM-IV & DSM-5). Meta-analysis of 476 risk ratios enabled 123 comparisons of diagnostic rates for specific disorders. Comparisons demonstrating diagnostic inflation (i.e., higher diagnostic rate in the later edition) did not exceed those demonstrating deflation. The average risk ratio was 1.00, indicating no overall change in diagnostic stringency from DSM-III to DSM-5, and there were no reliable tendencies for particular DSM revisions to be more inflationary or deflationary than others. Specific disorders showing reliable evidence of diagnostic inflation or deflation were identified. Notable examples of diagnostic inflation included Attention-Deficit/Hyperactivity Disorder (ADHD), autism, eating disorders, and substance dependence. Although serious concerns have been raised about diagnostic inflation or "concept creep" in the DSM, these concerns may have been overstated.

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BACKGROUND: Members of the family Mycetophilidae (Diptera) have life cycles that are typically associated with fungus. Their biology is relatively well known in the Palaearctic, though other regions are poorly known, and there are no associations recorded between mycetophilid immatures and fungi in the Neotropical region. Here we report the first association between a mycetophilid-Neoempheriapuncticoxa Edwards-and fungi in this region. Immatures of N.puncticoxa were collected on fungi and some were reared in the laboratory until adult emergence. The immature stages and adult of N.puncticoxa are described and re-described respectively, and high resolution images and illustrations of the habitus, wings, thorax, male and female terminalia, immatures, and in situ specimens are given. NEW INFORMATION: We report the first association between Mycetophilidae and fungi in the Neotropical region.

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We describe and illustrate a new species of biting midge belonging to the subgenus Forcipomyia (Microhelea), from the Estação Biológica de Boracéia, São Paulo State, Brazil. We include illustrations of the mouthparts, head, thorax, legs, abdominal setae, and habitus. The new species is similar to the few other recorded Neotropical species of biting midges, such as Forcipomyia (Microhelea) alleni, Forcipomyia (Microhelea) castneri, Forcipomyia (Microhelea) grandcolasi, and Forcipomyia (Microhelea) tettigonaris. However, it can be distinguished by the combination of external characters, such as the number of plates on the maxilla, the number of denticles on the mandible, the size of the labellum, and the morphology of the palpus. The two female specimens examined were found biting on a female stick bug, Paraphasma paulense (Phasmida: Pseudophasmatidae), which was attracted to a light trap.

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Larva and pupa of Loncophorus pustulatus (Champion, 1903) (Curculionidae: Curculioninae: Anthonomini) are described, illustrated and compared with descriptions of immatures of two other species of Loncophorus. Weevil larvae were found inside aborted flowers on the ground under Ceiba speciosa (A. St.-Hil.) Ravenna (Malvaceae), in the city of Sgo Paulo, State of S5o Paulo, and reared to adults in laboratory. Data obtained in the field and under laboratory conditions are presented. Parasitoidism of weevil larvae by wasps of the genus Catolaccus (Hymenoptera: Pteromalidae) is reported.

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