Growth Hormone Deficiency Following Traumatic Brain Injury in Pediatric and Adolescent Patients: Presentation, Treatment, and Challenges of Transitioning from Pediatric to Adult Services.

Abstract Traumatic brain injury (TBI) is increasingly recognized, with an incidence of approximately 110 per 100,000 in pediatric populations and 618 per 100,000 in adolescent and adult populations. TBI often leads to cognitive, behavioral, and physical consequences, including endocrinopathies. Deficiencies in anterior pituitary hormones (e.g., adrenocorticotropic hormone, thyroid-stimulating hormone, gonadotropins, and growth hormone [GH]) can negatively impact health outcomes and quality of life post-TBI. This review focuses on GH deficiency (GHD), the most common post-TBI pituitary hormone deficiency. GHD is associated with abnormal body composition, lipid metabolism, bone mineral density, executive brain functions, behavior, and height outcomes in pediatric, adolescent, and transition-age patients. Despite its relatively frequent occurrence, post-TBI GHD has not been well studied in these patients; hence, diagnostic and treatment recommendations are limited. Here, we examine the occurrence and diagnosis of TBI, retrospectively analyze post-TBI hypopituitarism and GHD prevalence rates in pediatric and adolescent patients, and discuss appropriate GHD testing strategies and GH dosage recommendations for these patients. We place particular emphasis on the ways in which testing and dosage recommendations may change during the transition phase. We conclude with a review of the challenges faced by transition-age patients and how these may be addressed to improve access to adequate healthcare. Little information is currently available to help guide patients with TBI and GHD through the transition phase and there is a risk of interrupted care; therefore, a strength of this review is its emphasis on this critical period in a patient's healthcare journey.

Emergency Preparedness of Secondary School Athletic Programs in Arizona.

CONTEXT: Schools that sponsor athletic programs have an obligation to provide a safe environment with appropriate policies for addressing emergencies. OBJECTIVE: To describe the emergency preparedness of secondary schools in Arizona specific to emergency action plans (EAPs), cardiac arrest, concussion, and heat illness. DESIGN: Cross-sectional study. SETTING: Online survey. PATIENTS OR OTHER PARTICIPANTS: Athletic directors from 143 Arizona secondary schools (response rate = 54%). INTERVENTION(S): A 6-section survey that included questions related to athletic trainer (AT) access, EAPs, automated external defibrillators (AEDs), concussion, heat illness, and other policies. MAIN OUTCOME MEASURE(S): Descriptive statistics were reported. Comparisons of responses between schools with and without AT access were conducted with Mann-Whitney U tests. RESULTS: Most respondents (81%, n = 116) indicated their school had access to an AT, and 95% (n = 125) of respondents reported their school had a written EAP. The AEDs were available at most (93%, n = 121) schools. All respondents were familiar with the interscholastic concussion policy, and 98% (n = 123) indicated they had a school-specific policy. Almost all respondents (99%, n = 121) reported being familiar with the state heat-illness policy. Environmental measures were taken before practices at 48% (n = 60) of schools. Schools with access to an AT were more likely to have an EAP, venue-specific EAPs, physician approval of EAPs, AEDs, heat-illness policies, and cold-water immersion tubs and to take environmental measures. CONCLUSIONS: Whereas the majority of schools reported AT access, not all schools had adequate EAPs in place. Schools would benefit from educational opportunities regarding best practices and policy development to improve emergency preparedness.

Traumatic Brain Injury in Domestic Violence Victims: A Retrospective Study at the Barrow Neurological Institute.

Domestic violence is a national health crisis, which affects people of all ages, races, and socioeconomic classes. Traumatic brain injury is common in victims because of the high frequency of head and neck injuries inflicted through abuse. These recurrent injuries can lead to chronic symptoms with high morbidity. We conducted a retrospective chart review of 115 patients with a history of head trauma as a result of domestic violence. All patients were seen in a subspecialty traumatic brain injury clinic, at which time information regarding their histories and self-reported symptoms were recorded. In total, 109 females and 6 males were included in our study, with an age range of 4-68 years. Overall, 88% reported more than one injury and 81% reported a history of loss of consciousness associated with their injuries. Only 21% sought medical help at the time of injury. Whereas 85% had a history of abuse in adulthood, 22% had experienced abuse in both childhood and adulthood, and 60% of the patients abused as children went on to be abused as adults. Headache was the most common chief complaint, but on a self-reported symptom severity scale, behavioral symptoms were the most severe. Psychiatric disease was present in 84% of patients. Traumatic brain injury is a frequent sequela of domestic violence, from which many victims sustain multiple injuries without seeking medical care. Brain injuries are often sustained over many years and lead to lasting physical, behavioral, and cognitive consequences. Better understanding of these injuries will lead to improved care for this population.

Pediatric stroke.

INTRODUCTION: Pediatric stroke, while increasingly recognized among practitioners as a clinically significant, albeit infrequent entity, remains challenging from the viewpoint of clinicians and researchers. DISCUSSION: Advances in neuroimaging have revealed a higher prevalence of pediatric stroke while also provided a safer method for evaluating the child's nervous system and vasculature. An understanding of pathogenic mechanisms for pediatric stroke requires a division of ages (perinatal and childhood) and a separation of mechanism (ischemic and hemorrhagic). This article presents a review of the current literature with the recommended divisions of age and mechanism. CONCLUSION: Guidelines for treatment, though limited, are also discussed.

Sydenham's chorea as a presentation of Moyamoya disease.

A seven year-old male presented to his pediatrician with choreiform movements and a recent history of sore throat. He was diagnosed with Sydenham's chorea based on clinical criteria and laboratory evidence. Worsening symptoms prompted a magnetic resonance imaging (MRI) of the brain which demonstrated evidence of Moyamoya disease. Sydenham's chorea is a common and well-documented complication of post-streptococcal infection, but has not been previously reported in association with Moyamoya disease. This case raises the quandary of causality of chorea in this patient and the need for neuroimaging in children with movement disorders.

Compound heterozygous polymerase gamma gene mutation in a patient with Alpers disease.

Alpers disease is a mitochondrial depletion syndrome characterized by psychomotor retardation, intractable epilepsy, and liver failure. Polymerase gamma (POLG) gene mutations are a known cause of the disease. We describe a case in which a 14-month-old female presented with epilepsia partialis continua evolving into generalized status epilepticus. Treatment with multiple antiepileptic medications and the ketogenic diet eliminated her seizures, but she remained severely encephalopathic. Magnetic resonance imaging showed diffuse atrophy of gray-matter structures. She ultimately developed liver failure and died. Mitochondrial analysis revealed compound heterozygosity for 3 POLG gene mutations, 2 of which were previously unreported.

Intravenous levetiracetam in children with seizures: a prospective safety study.

In 2006, intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy, 16 years or older. We have established the safety, tolerability, and dosage of intravenous levetiracetam in children. This prospective study included 30 children (6 months to <15 years of age). Patients were administered a single dose of intravenous levetiracetam (50 mg/kg, maximal dose 2500 mg) over 15 minutes. A blood level of levetiracetam was performed 10 minutes after the infusion. The treated children's average age was 6.3 years (range 0.5-14.8 years). The mean levetiracetam level was 83.3 microg/mL (range 47-128 microg/mL). There were no serious adverse reactions. Minor reactions included sleepiness, fatigue, and restlessness. An apparent decrease in seizure frequency across all seizure types was noted. The dose of 50 mg/kg was well tolerated by the patients and is a safe, appropriate loading dose.

Reversible lamotrigine-induced neurobehavioral disturbances in children with epilepsy.

A retrospective review was performed in patients who developed neurobehavioral adverse reactions to lamotrigine. Data were obtained from interviews, examinations, and routine medical records. There were 7 male and 2 female patients with epilepsy with a mean age of 5 years. All 9 patients became hyperactive and agitated over a broad range of lamotrigine dosing (0.7-14.0 mg/kg per d). Five patients developed self-injurious and violent behaviors. Two patients developed severe insomnia. The most affected patient was a 6-year-old boy whose mood and affect became extremely volatile. He also experienced threatening visual and auditory hallucinations and insomnia. All 9 patients had dramatic improvement and/or resolution of the adverse neurobehavioral effects following discontinuation or reduction of lamotrigine. Reversible, severe neurobehavioral disturbances associated with lamotrigine therapy have not been reported in the literature. While idiosyncratic and uncommon, this is a potentially significant, clinical side effect. Further studies are necessary to clarify the population at risk.

Osmotic demyelination syndrome as a consequence of treating hyperammonemia in a patient with ornithine transcarbamylase deficiency.

A 7-year-old female patient with a new diagnosis of ornithine transcarbamylase deficiency was treated for hyperammonemia with a standard protocol. Several days later, she developed ataxia, dysmetria, and dysarthria. Magnetic resonance imaging of the brain demonstrated pontine and extrapontine white matter changes consistent with osmotic demyelination. Classically described as a consequence of hyponatremia treatment, osmotic demyelination syndrome has rarely been associated with other entities. This case suggests a potentially serious complication of the standard therapy for hyperammonemia in patients with ornithine transcarbamylase deficiency.

Hemimegalencephaly in a patient with a neurocutaneous syndrome.

A 5-year-old girl with a history of hypomelanosis of Ito and intractable epilepsy was evaluated for possible resective surgery. Magnetic resonance imaging showed an enlarged right hemisphere, whereas electrographic seizures were arising from the right hemisphere or had a generalized onset. The patient was believed to be a good candidate for hemispherectomy, but the family was hesitant and started a modified Atkins diet. Her seizure control has improved, but she continues to have weekly seizures. Hypomelanosis of Ito is a well-known cause of hemimegalencephaly and is often associated with intractable epilepsy and hemiparesis. Hemispherectomy can often be an effective treatment in intractable cases.

Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function.

We have identified a lethal phenotype characterized by sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males [Online Mendelian Inheritance in Man (OMIM) accession no. 608800]. Twenty-one affected individuals with this autosomal recessive syndrome were ascertained in nine separate sibships among the Old Order Amish. High-density single-nucleotide polymorphism (SNP) genotyping arrays containing 11,555 single-nucleotide polymorphisms evenly distributed across the human genome were used to map the disease locus. A genome-wide autozygosity scan localized the disease gene to a 3.6-Mb interval on chromosome 6q22.1-q22.31. This interval contained 27 genes, including two testis-specific Y-like genes (TSPYL and TSPYL4) of unknown function. Sequence analysis of the TSPYL gene in affected individuals identified a homozygous frameshift mutation (457_458insG) at codon 153, resulting in truncation of translation at codon 169. Truncation leads to loss of a peptide domain with strong homology to the nucleosome assembly protein family. GFP-fusion expression constructs were constructed and illustrated loss of nuclear localization of truncated TSPYL, suggesting loss of a nuclear localization patch in addition to loss of the nucleosome assembly domain. These results shed light on the pathogenesis of a disorder of sexual differentiation and brainstem-mediated sudden death, as well as give insight into a mechanism of transcriptional regulation.