To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid ...tic disorders.
Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks.
Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures.
Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.
To determine the prevalence, age of onset, and risk factors for overweight and obesity in children with congenital heart disease (CHD).
Children with CHD who were seen at our institution from 1996 to ...2017 were studied. Patients were full-time residents of the United States and were receiving all cardiac care at our institution. Patients were categorized by age and CHD diagnosis. The date of last normal weight for age and the date of first recorded weight in the range of overweight and obese were documented.
Nine hundred sixty-eight patients with CHD were included. The prevalence of overweight and obesity was 31.5% and 16.4%, respectively. For patients who became overweight or obese, the last recorded normal weight was between 6 and 10 years of age. Electrophysiologic disease and older age were risk factors for obesity.
Children with CHD have an increasing risk of becoming overweight and obese in early childhood. This study provides important information and identifies critical period to implement preventative measures and counsel families about the risk of obesity in CHD.
Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of ...definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.
Physiologic indices that reflect intracellular Ca2+ cycling were chosen to evaluate contraction and relaxation properties of the univentricular heart. We hypothesized that these indices would be ...impaired in univentricular hearts. With advances in surgical palliation, an increasing number of children are surviving with univentricular hearts supporting the systemic circulation. Similar to the adult failing heart, single ventricles may also manifest impaired Ca2+ cycling, which may have important therapeutic implications. In our study, we did not actually measure Ca2+ uptake or transients in the cardiac myocyte. Rather, we used previously validated physiologic indices that are known to reflect Ca2+ cycling. Sixteen children were studied, eight with single ventricles (SV) and eight as matched control subjects. Systolic properties were studied using maximal derivative of ventricular pressure (dP/dtmax), force-frequency relationship, and mechanical restitution. Diastolic properties were assessed using time constant of relaxation (tau) and the relaxation-frequency relationship. The critical HR (HRcrit) was assessed from the force-frequency relationship and relaxation-frequency relationship. DP/dtmax and tau were calculated from micromanometric tracings at increasing HRs, generated by right atrial pacing. In SV patients, dP/dtmax was lower than in the control group at each matched HR, and the force-frequency relationship was shifted downward. Restitution of contractility was slower in patients with SV. Tau was similar in both groups at lower HRs but significantly prolonged in the SV group at faster HRs. In the SV, HRcrit was significantly shifted to the left. These findings indicate impaired systolic and diastolic properties of univentricular heart, especially at increased HRs. Because these physiologic indices reflect Ca2+ cycling, it is speculated that the phenomenon of Ca2+ cycling may be impaired in the myocytes of univentricular hearts.
Initial reports described Tourette syndrome as a lifelong disorder. Since then, others have noted that some patients experience remissions during late adolescence. To examine this issue, we sent ...questionnaires to 99 patients with Tourette syndrome who were 15 to 25 years old. The majority of the 58 respondents indicated that they had fewer tics as they reached late adolescence or young adulthood. Although most reported associated behavior or learning problems, the majority felt they were coping well. The long-term outcome in many patients with Tourette syndrome may be more optimistic than previously reported.
Background Tourette Syndrome (TS) has a complex etiology and wide variability in phenotypic expression. Identifying underlying symptom patterns may be useful for etiological and outcome studies of ...TS. Methods Lifetime tic and related symptom data were collected between 1996 and 2001 in 121 TS subjects from the Central Valley of Costa Rica and 133 TS subjects from the Ashkenazi Jewish (AS) population in the US. Subjects were grouped by tic symptoms using an agglomerative hierarchical cluster analysis. Cluster membership was tested for association with available ancillary information (age of onset, tic severity, comorbid disorders, medication treatment and family history). Results Cluster analysis identified two distinct groups in each sample, those with predominantly simple tics (cluster 1), and those with multiple complex tics (cluster 2). Membership in cluster 2 was correlated with increased tic severity, global impairment, medication treatment, and presence of comorbid obsessive-compulsive symptoms in both samples, and with family history of tics, lower verbal IQ, earlier age of onset, and comorbid obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in the AS sample. Conclusions This study provides evidence for consistent and reproducible symptom profiles in two independent TS study samples. These findings have implications for etiological studies of TS.
This is the first epilepsy surgery series to analyze the definition of "completeness" of resection, based solely on results of chronic scalp and subdural EEG recording. When patients had complete ...removal of all cortical areas with ictal and interictal epileptiform discharges, the clinical outcome was usually good. When areas with epileptiform discharges were left behind, good outcome was significantly less frequent. This correlation between complete resection and good outcome was independent of the presence or absence of CT-detected structural lesions or sharp waves on post-resection electrocorticography. These results support completeness of resection, defined by prolonged extraoperative EEG, as an important factor in seizure surgery.
Psychogenic seizures in 21 nonepileptic children and adolescents, aged 8 to 18 (mean 14.5) years, were recorded by means of video recording and electroencephalography. The episodes included thrashing ...movements, limb jerking, or staring, with unresponsiveness. Ictal and interictal electroencephalograms showed no abnormalities after antiepileptic medication was discontinued. Fifteen patients had psychogenic seizures spontaneously during recording, and six had seizures in response to suggestion and intravenous saline injection. After the video-electroencephalographic evaluation, patients and families were told that the episodes were emotional in origin. All patients but 1 agreed to remain without antiepileptic medication, and 16 patients (76%) agreed to begin psychiatric treatment. At 6 to 66 (mean 30) months' follow-up, 14 of 18 (78%) were free of episodes. These data indicate that the majority of young patients with psychogenic seizures have a good outcome. A firm diagnosis is critical so that the episodes can be classified and emphasized as medically not worrisome, permitting a shift away from antiepileptic medication and toward psychiatric treatment.
PDF
