Heterogeneity of persisting symptoms after sport-related concussion (SRC): exploring symptom subtypes and patient subgroups.

This study aimed to explore the heterogeneity of persisting symptoms after sport-related concussion (SRC). We examined the structure of symptom subtypes within 163 patients with SRC (M = 16.7 weeks post-injury). Subsequently, we investigated the existence of subgroups of patients based on comparable configuration of co-occurring symptom subtypes. To explore factors that may contribute to the emergence of SRC patient subgroups, subgroups were compared on pre-injury (i.e., demographics and medical history), personality (Severity Indices of Personality Problems Short Form) and SRC characteristics (i.e., history of prior concussions, loss of consciousness and post-traumatic amnesia). To investigate the relevance of SRC subgrouping for clinical outcome, subgroups were compared on symptom severity (Sport Concussion Assessment Tool 5). The results provide empirical evidence for the existence of symptom subtypes, characterized as a: neurocognitive, fatigue, emotional, migraine and vestibular-ocular symptom subtype in patients with persisting SRC. Study results also showed evidence for the existence of SRC subgroups of patients with a comparable configuration of co-occurring prevailing symptom subtypes, including a neurocognitive-migraine, fatigue, migraine-emotional and neurocognitive-emotional subgroup. The subgroups differed on pre-injury, personality and SRC characteristics, suggesting that these factors may contribute to the emergence of specific SRC patient subgroups. The subgroups also differed in the severity of persisting symptoms, highlighting the clinical relevance of SRC subgrouping. These results support the idea that patient subgroups with persisting SRC with a comparable pattern of co-occurring symptom subtypes exists, which may require targeted prognosis, clinical management and treatment to optimize recovery.

Differential effects of long-term aerobic versus cognitively-engaging physical activity on children's visuospatial working memory related brain activation: A cluster RCT.

Different types of physical activity are thought to differentially affect children's brain activation, via physiological mechanisms, or by activating similar brain areas during physical and cognitive tasks. Despite many behavioral studies relying on these mechanisms, they have been rarely studied. This study looks at both mechanisms simultaneously, by examining effects of two physical activity interventions (aerobic vs. cognitively-engaging) on children's brain activation. Functional Magnetic Resonance Imaging (fMRI) data of 62 children (48.4% boys, mean age 9.2 years) was analyzed. Children's visuospatial working memory related brain activity patterns were tested using a Spatial Span Task before and after the 14-week interventions consisting of four physical education lessons per week. The control group followed their regular program of two lessons per week. Analyses of activation patterns in SPM 12.0 revealed no activation changes between pretest and posttest (p > .05), and no differences between the three conditions in pretest-posttest changes in brain activation (p > .05). Large inter-individual differences were found, suggesting that not every child benefited from the interventions in the same way. To get more insight into the assumed mechanisms, further research is needed to understand whether, when, for whom, and how physical activity results in changed brain activation patterns.

Relationships between gross motor skills, cardiovascular fitness, and visuospatial working memory-related brain activation in 8- to 10-year-old children.

Relationships between gross motor skills and cardiovascular fitness with visuospatial working memory (VSWM) in children are hypothesized to be mediated by underlying functional brain mechanisms. Because there is little experimental evidence to support this mechanism, the present study was designed to investigate the relationships of gross motor skills and cardiovascular fitness with VSWM-related brain activation in 8- to 10-year-old children. Functional magnetic resonance imaging data obtained during a VSWM-task were analyzed for 80 children from grades 3 (47.5%) and 4 of 21 primary schools in the Netherlands (51.3% girls). Gross motor skills (Korper Koordinationstest für Kinder and Bruininks-Oseretsky Test of Motor Proficiency - 2nd Edition) and cardiovascular fitness (20-meter Shuttle Run Test) were assessed. VSWM-related brain activation was found in a network involving the angular gyrus, the superior parietal cortex, and the thalamus; deactivation was found in the inferior and middle temporal gyri. Although behavioral results showed significant relations of gross motor skills and cardiovascular fitness with VSWM performance, gross motor skills and cardiovascular fitness were not related to VSWM-related brain activation. Therefore, we could not confirm the hypothesis that brain activation underlies the relationship of gross motor skills and cardiovascular fitness with VSWM performance. Our results suggest that either the effects of physical activity on cognition do not necessarily go via changes in gross motor skills and/or cardiovascular fitness, or that brain activation patterns as measured with the blood-oxygen-level dependent (BOLD) signal may not be the mechanism underlying the relationships of gross motor skills and cardiovascular fitness with VSWM.

Subtypes of Sport-Related Concussion: a Systematic Review and Meta-cluster Analysis.

OBJECTIVE: Current clinical guidelines provide a unitary approach to manage sport-related concussion (SRC), while heterogeneity in the presentation of symptoms suggests that subtypes of SRC may exist. We systematically reviewed the available evidence on SRC subtypes and associated clinical outcomes. DATA SOURCES: Ovid Medline, Embase, PsycINFO, and SPORTDiscus ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Electronic databases were searched for studies: (i) identifying SRC symptom clusters using classification methodology; or (ii) associating symptom clusters to clinical outcome variables. A total of 6,146 unique studies were identified, of which 75 full texts were independently assessed by two authors for eligibility. A total of 22 articles were included for systematic review. DATA EXTRACTION: Two independent authors performed data extraction and risk of bias analysis using the Cochrane Collaboration tool. DATA SYNTHESIS: Six studies found evidence for existence of SRC symptom clusters. Combining the available literature through Multiple Correspondence Analysis (MCA) provided evidence for the existence of a migraine cluster, a cognitive-emotional cluster, a sleep-emotional cluster, a neurological cluster, and an undefined feelings cluster. Nineteen studies found meaningful associations between SRC symptom clusters and clinical outcomes. Clusters mapping to the migraine cluster were most frequently reported in the literature and were most strongly related to aspects of clinical outcome. CONCLUSIONS: The available literature provides evidence for the existence of at least five subtypes in SRC symptomatology, with clear relevance to clinical outcome. Systematically embedding the differentiation of SRC subtypes into prognosis, clinical management, and intervention strategies may optimize the recovery from SRC.

Feedback learning and behavior problems after pediatric traumatic brain injury.

BACKGROUND: Feedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI). METHOD: Children aged 6-13 years diagnosed with TBI (n = 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n = 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF- TBI, n = 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+ TBI, n = 51) and moderate/severe TBI (n = 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored. RESULTS: No evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p = 0.03, d = -0.51). Furthermore, the mildRF+ TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's ⩽ 0.04, d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p = 0.006, d = 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p = 0.03, ß = -0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77, p = 0.001). CONCLUSIONS: Moderate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.

Intelligence after traumatic brain injury: meta-analysis of outcomes and prognosis.

Worldwide, 54-60 million individuals sustain traumatic brain injury (TBI) each year. This meta-analysis aimed to quantify intelligence impairments after TBI and to determine the value of age and injury severity in the prognosis of TBI. An electronic database search identified 81 relevant peer-reviewed articles encompassing 3890 patients. Full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ) impairments were quantified (Cohen's d) for patients with mild, moderate and severe TBI in the subacute phase of recovery and the chronic phase. Meta-regressions explored prognostic values of age and injury severity measures for intelligence impairments. The results showed that, in the subacute phase, FSIQ impairments were absent for patients with mild TBI, medium-sized for patients with moderate TBI (d = -0.61, P < 0.001) and large for patients with severe TBI (d = -1.09, P < 0.001). In the chronic phase, FSIQ impairments were small for patients with mild or moderate TBI (d = -0.37 and -0.19, P ≤ 0.008) and large for patients with severe TBI (d = -0.80, P < 0.001). Adults with mild TBI had larger PIQ and VIQ impairments in the chronic phase than children (both Q ≥ 5.21, P ≤ 0.02), whilst children with severe TBI had larger FSIQ and VIQ impairments than adults (both Q ≥ 4.40, P ≤ 0.04). Glasgow Coma Scale score, duration of loss of consciousness and post-traumatic amnesia duration moderately to strongly predicted FSIQ, PIQ and VIQ impairments (0.41 ≤ r ≤ 0.82, P ≤ 0.02), but no differences in predictive value were observed. In conclusion, TBI causes persisting intelligence impairments, where children may have better recovery from mild TBI and poorer recovery from severe TBI than adults. Injury severity measures predict intelligence impairments and do not outperform one another.

Effects of the mycotoxin fumonisin B(1) on cell death in human kidney cells and human lung fibroblasts in primary culture.

Fumonisins are mycotoxins produced by Fusarium verticillioides. The toxic effects of fumonisin B(1) (FB(1)) at the cellular level consist of a mixture of both necrosis and apoptosis. We studied the effect of FB(1) in human lung fibroblasts (NHLF) and human kidney epithelial cells (RPTEC) in primary culture. Apoptotic and necrotic cell death, collagen and fibronectin secretion were determined mainly after 14 days' exposure. The protein content of NHLF and RPTEC cells was slightly increased after 14 days' exposure to low FB(1) concentrations (0.1 or 1 microm). Caspase-3 activity tended to increase in NHLF and to decrease in RPTEC cells with higher FB(1) concentrations after 14 days' exposure. LDH release was slightly decreased in both cell types after 14 days. Collagen I and III secretion was enhanced in NHLF cells. Collagen III was decreased in RPTEC. Collagen IV was not changed in both cell types. Fibronectin secretion was uninfluenced in RPTEC and interim increased in NHLF. Furthermore LC-MS/MS studies did not give any hints for a metabolism of FB(1). Therefore, the main risk of prolonged FB(1) exposure seems to be altered collagen secretion pattern.

Treatment of skin defects using suspensions of in vitro cultured keratinocytes.

The in vitro cultivation of keratinocytes and their application in the form of confluent sheets to cover various kinds of skin defects involves a number of problematical steps which could be improved by using single cell suspensions instead. Therefore we developed a method to apply keratinocytes suspended as single cells in a fibrin gel. By testing the feasibility of this method in different experimental animal models we found that it facilitates cultivation as well as application of the cells, moreover, this method allows a much more flexible use of the cells, i.e. it is easier to consider the clinical condition of the patient than by the conventional method.