Adolescent with Rhabdomyolysis due to Undiagnosed Hypothyroidism

Exercise-induced rhabdomyolysis has been described in military recruits, trained athletes and daily runners. Statin use, quail ingestion, infection by Epstein-Barr virus (EBV), and hypothyroidism, though rare, are risk factors for the development of rhabdomyolysis. We describe the case of a 15-year-old female who presented with myalgias, weakness, and pigmenturia following marching band practice. Laboratory tests confirmed an elevated creatine kinase (CK) level as well as a profound hypothyroid state. Muscle biopsy revealed severe muscle necrosis and myositis. Treatment with levothyroxine resulted in obtaining an euthyroid state and regain of muscle strength as well as decrease in CK levels. Although rare, hypothyroidism should be considered as a potential cause of rhabdomyolysis in pediatric patients undergoing a myopathy workup

Mortality After Pediatric Arterial Ischemic Stroke

OBJECTIVES: Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS). METHODS: Neonates (0-28 days) and children (29 days- < 19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry. Death during hospitalization and cause of death were ascertained from medical records. Logistic regression was used to analyze associations between risk factors and in-hospital mortality. RESULTS: Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were strokerelated, with remaining deaths attributed to medical disease. In multivariable analysis, congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI] : 1.23-12.29; P = .021), posterior plus anterior circulation stroke (OR: 5.36; 95% CI: 1.70-16.85; P = .004), and stroke presentation without seizures (OR: 3.95; 95% CI: 1.26-12.37; P = .019) were associated with in-hospital mortality for neonates. Hispanic ethnicity (OR: 3.12; 95% CI: 1.56-6.24; P = .001), congenital heart disease (OR: 3.14; 95% CI: 1.75-5.61; P < .001), and posterior plus anterior circulation stroke (OR: 2.71; 95% CI: 1.40-5.25; P = .003) were associated with in-hospital mortality for children. CONCLUSIONS: In-hospital mortality occurred in 2.6% of pediatric AIS cases. Most deaths were attributable to stroke. Risk factors for in-hospital mortality included congenital heart disease and posterior plus anterior circulation stroke. Presentation without seizures and Hispanic ethnicity were also associated with mortality for neonates and children, respectively. Awareness and study of risk factors for mortality represent opportunities to increase survival

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

Postconcussive Symptoms After Single and Repeated Concussions in 10- to 20-Year-Olds: A Cross-Sectional Study

The objective was to characterize cognitive deficits and postconcussive symptoms in a pediatric population with no concussion, a single concussion, and ≥2 concussions, using a cross-sectional design. Cognitive function and postconcussive symptoms were assessed in participants (age 10-20) with no concussion (n = 1118), single concussion (n = 368), and repeated (≥2) concussions (n = 252). Analyses were adjusted for age and gender. Individuals with ≥2 concussions exhibited more total postconcussive symptoms; more loss of consciousness, amnesia and confusion; more headaches; and poorer cognitive function compared to no concussion and single concussion. Postconcussive symptoms may play a modulatory role in cognitive dysfunction after repeated concussions as those with loss of consciousness, amnesia, confusion, or headaches exhibited worse verbal memory, visual memory, visual-motor processing, and poorer impulse control compared to those without these symptoms. This analysis demonstrates that repeated concussions is associated with poorer cognitive function and postconcussive symptoms compared to a single concussion

Gender differences in sleep symptoms after repeat concussions

There are notable gender differences in concussion as well as sleep. Sleep disturbance is a major symptom of post-concussive syndrome. The interplay between sleep disturbance, concussion, and gender has yet to be examined. The objective of this study was to determine whether sleep disturbance plays a role in the known gender differences associated with concussion.Males and females (ages 10-35 years) completed a pre-concussion and post-concussion evaluation. Levels of sleep disturbance were assessed at baseline (N&nbsp;=&nbsp;1284), after first concussion (N&nbsp;=&nbsp;432) and after repeated concussions (one or more concussions, N&nbsp;=&nbsp;296). Sleep disturbance levels were also compared among males and females with headaches, mood changes, and cognitive dysfunction. Analyses included group comparisons and correlations of post-concussive symptoms and cognitive dysfunction, respectively. Data was adjusted for age.Compared to males, females reported higher levels of sleep disturbance after a single concussion; however, levels of sleep disturbance equalized after repeated concussions. Females with higher levels of sleep disturbance had more headaches and more mood changes requiring medical treatment, compared to males. In addition, sleep disturbance was more strongly correlated with cognitive dysfunction in females compared to males.Gender differences in concussion recovery after repeat concussions may be primarily due to a difference in sleep disturbance between the genders. This difference in sleep appears to moderate the levels of other post-concussive symptoms. This indicates that sleep disturbance should be closely monitored and treated in females after a concussion. Further studies are required to determine the underlying reasons for these gender differences

High Sleep Disturbance and Longer Concussion Duration in Repeat Concussions

Objectives: The relationship between repeated concussions and sleep disturbance is yet to be fully understood. The objective of this study was to examine the relationship between sleep disturbance, concussion duration, and repeated concussions by assessing postconcussive symptoms and cognition. Methods: Subjects (ages 13-33&nbsp;years) underwent postconcussion cognitive function evaluation and reported postconcussion symptoms including severity of disturbed sleep (drowsiness, trouble falling asleep, sleeping more than usual, and sleeping less than usual), mood disturbance (sadness, irritability, nervousness, and emotional lability), and headache. Data on cognitive function and concussive symptoms were collected for 430 subjects after first concussion, 192 subjects after second concussion, and 118 subjects after three or more concussions. A subset of subjects (119) were monitored longitudinally to assess concussion duration. Analyses included group comparisons, regression, and correlation; data were adjusted for age and gender. Results: Sleep disturbance differed significantly by group (mean[SEM]: 1st concussion&nbsp;=&nbsp;2.56[0.2]; 2nd concussion&nbsp;=&nbsp;3.65[0.34]; 3+&nbsp;concussions&nbsp;=&nbsp;4.32[0.43]). Concussion history predicts concussion duration (R2&nbsp;=&nbsp;0.20, F[1,116]&nbsp;=&nbsp;27.33, p &lt;&nbsp;0.001). Furthermore, trouble falling asleep (β&nbsp;=&nbsp;0.15) and sleeping less than usual (β&nbsp;=&nbsp;0.15) predicted concussion duration (R2&nbsp;=&nbsp;0.062, F[1,116]&nbsp;=&nbsp;3.15, p =&nbsp;0.047). Reported sleep disturbance after repeated concussions was higher in patients with higher headache (F[2,732]&nbsp;=&nbsp;3.15, p =&nbsp;0.043) and mood disturbance (F[2,733]&nbsp;=&nbsp;3.35, p =&nbsp;0.036) severity. In addition, after repeated concussions, the positive correlation between sleep disturbance and cognitive dysfunction strengthened. Conclusions: History of repeated concussion is associated with longer concussion duration and higher reported sleep disturbance. Furthermore, those with sleep disturbance after repeated concussion exhibit more severe headaches, mood disturbance, and cognitive dysfunction.Abbreviations: ImPACT: Immediate Postconcussion Assessment and Cognitive Assessment (ImPACT); this is a computer-based test that assesses an individual's cognitive function and cumulatively documents current concussion symptoms. PCSS: Post Concussion Symptom Scale; this scale assesses the severity of concussion symptoms. SPSS: Statistical Package for Social Sciences. This is a statistical software package

Postconcussive Symptoms After Single and Repeated Concussions in 10- to 20-Year-Olds: A Cross-Sectional Study

The objective was to characterize cognitive deficits and postconcussive symptoms in a pediatric population with no concussion, a single concussion, and ≥2 concussions, using a cross-sectional design. Cognitive function and postconcussive symptoms were assessed in participants (age 10-20) with no concussion (n = 1118), single concussion (n = 368), and repeated (≥2) concussions (n = 252). Analyses were adjusted for age and gender. Individuals with ≥2 concussions exhibited more total postconcussive symptoms; more loss of consciousness, amnesia and confusion; more headaches; and poorer cognitive function compared to no concussion and single concussion. Postconcussive symptoms may play a modulatory role in cognitive dysfunction after repeated concussions as those with loss of consciousness, amnesia, confusion, or headaches exhibited worse verbal memory, visual memory, visual-motor processing, and poorer impulse control compared to those without these symptoms. This analysis demonstrates that repeated concussions is associated with poorer cognitive function and postconcussive symptoms compared to a single concussion