ABSTRACT
OBJECTIVE: To examine the association of home and neighborhood environment with neurobehavioral outcomes after severe pediatric traumatic brain injury (TBI). SETTING: Domestic and international children's medical centers. PARTICIPANTS: Participants enrolled in the study were 18 years or younger at the time of their severe TBI (Glasgow Coma Scale [GCS] ≤ 8), admitted to the intensive care unit, and underwent placement of an intracranial pressure (ICP) monitor. Exclusionary criteria included less severe injury (GCS > 8), pregnancy, and/or ICP monitor placement occurred at a non-participating hospital. DESIGN: A multicenter, observational cohort study. MAIN MEASURES: Outcomes assessed at 12 months post-injury included measures of global functioning, intellectual ability, caregiver-report measures of family functioning, executive functioning behaviors, behavior problems, and health-related quality of life. We examined mortality risk (assessed acutely after injury), family functioning (assessed at 12 months post-injury) and parenting practices, social environment, and neighborhood stressors (all assessed > 12 months post-injury), as correlates and moderators of the 12-month post-injury outcomes. RESULTS: Home and neighborhood factors were associated with neurobehavioral outcomes (ie, intellectual ability, executive functioning, behavioral adjustment, and health-related quality of life) but not with global functioning outcomes. A negative association between a more vulnerable home and neighborhood environment and neurobehavioral outcomes was more consistent in older children compared with younger children, based on age of injury. The influence of mortality risk on neurobehavioral outcomes was variable. CONCLUSION: Parenting practices and quality of social and neighborhood environment are associated with neurobehavioral outcomes 12 months after severe pediatric TBI. More research is needed to better understand the relationship between home/neighborhood stressors and TBI recovery to develop and implement strategies for patients and families to optimize outcomes. Future intervention development should focus on addressing parenting practices and social environment in a developmentally sensitive way for children who have sustained a severe TBI.
ABSTRACT
Long-read sequencing (LRS) technologies have been recently introduced to overcome intrinsic limitations of widely-used next-generation sequencing (NGS) technologies, namely the sequencing limited to short-read fragments (150-300 base pairs). Since its introduction, LRS has permitted many successes in unraveling hidden mutational mechanisms. One area in clinical neurology in need of rethinking as it applies to genetic mechanisms is essential tremor (ET). This disorder, among the most common in neurology, is a syndrome often exhibiting an autosomal dominant pattern of inheritance whose large phenotypic spectrum suggest a multitude of genetic etiologies. Exome sequencing has revealed the genetic etiology only in rare ET families (FUS, SORT1, SCN4A, NOS3, KCNS2, HAPLN4/BRAL2, and USP46). We hypothesize that a reason for this shortcoming may be non-classical genetic mechanism(s) underpinning ET, among them trinucleotide, tetranucleotide, or pentanucleotide repeat disorders. In support of this hypothesis, trinucleotide (e.g., GGC repeats in NOTCH2NLC) and pentanucleotide repeat disorders (e.g., ATTTC repeats in STARD7) have been revealed as pathogenic in patients with a past history of what has come to be referred to as "ET plus," bilateral hand tremor associated with epilepsy and/or leukoencephalopathy. A systematic review of LRS in neurodegenerative disorders showed that 10 of the 22 (45%) genetic etiologies ascertained by LRS include tremor in their phenotypic spectrum, suggesting that future clinical applications of LRS for tremor disorders may uncover genetic subtypes of familial ET that have eluded NGS, particularly those with associated leukoencephalopathy or family history of epilepsy. LRS provides a pathway for potentially uncovering novel genes and genetic mechanisms, helping narrow the large proportion of "idiopathic" ET.