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Transcranial Alternating Current Stimulation at 40 Hz Improves Social Functioning in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

BACKGROUND: Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS: In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happ&#xe9; animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS: The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group &#xd7; time interaction. No serious adverse events occurred. CONCLUSIONS: These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Humans↗

Echocardiographic characteristics of secundum-type atrial septal defects in adult patients: implications for percutaneous closure using Amplatzer septal occluders.

The aim of the study was to analyze echocardiographic characteristics of isolated secundum-type atrial septal defects (ASD II) in adult patients and their implications for percutanous closure using Amplatzer septal occluders. The study population consisted of 64 consecutive adult patients with isolated ASD II (mean age 43.6 +/- 15.9 years). Patients were evaluated using both transthoracic and transesophageal echocardiography. Defects in 29 of 64 patients (45.3%) fulfilled the echocardiographic criteria for percutaneous closure. The mean defect diameter in the study was 22.2 +/- 9.5 mm. In all, 13 morphologic variations of ASD II were detected. A statistically significant correlation between defect size and the number of deficient defect rims was found. Less than 50% of ASD II in adult patients fulfilled the echocardiographic criteria for percutaneous closure using Amplatzer septal occluders. Because others have demonstrated growth of ASD II over time, we presume that in some patients, defect growth is associated with attenuation or even disappearance of defect rims causing changing defect morphology with increasing defect size.

Adult↗

Accidental sizing of patent foramen ovale during atrial septal defect sizing for device.

A 21 year old lady with a 22 mm secundum atrial septal defect with adequate rims, and thin septum at the region of the fossa ovalis, but no additional atrial septal defect by transthoracic and transoesophageal echocardiogram was taken up for ASD sizing with a view to device closure. Initially, the ASD was sized to only 8 mm. However, the distal balloon was not fully opened out, and seemed to be conical with restricted opening. Inadvertent passage of sizing balloon through a patent foramen ovale (PFO) was immediately confirmed by transthoracic echocardiogram. The ASD was then recrossed and sized to 24 mm with normal opening out of the distal balloon. This was confirmed by transthoracic echocardiogram. A 28 mm ASD device was deployed across the ASD under transthoracic echocardiographic guidance with no residual flow.

Adult↗

Intracardiac echocardiography-guided transcatheter closure of secundum atrial septal defect: a new efficient device selection method.

OBJECTIVES: We assessed the use of intracardiac echocardiography (ICE) as the primary means for both selection of the Amplatzer Septal Occluder (ASO) and the guidance of transcatheter closure of secundum atrial septal defects (ASDs). BACKGROUND: The standard method for transcatheter closure of ASDs requires balloon-sizing maneuver and transesophageal echocardiographic (TEE) monitoring. The role of ICE during transcatheter closure of ASDs has not yet been established. METHODS: In 91 patients with ASDs, two standardized orthogonal sections were used to obtain ICE-derived measurements of the fossa ovalis and to assess optimal device deployment: the transverse section on the aortic valve plane, and the longitudinal section on the four-chamber plane. RESULTS: In all patients, ICE planes were identified with excellent resolution, providing proper measurements of the fossa ovalis, from which to derive geometric assumptions for the selection of an appropriately sized device. The ASO waist diameter was chosen on the basis of the r value (r = [square root c(2) + p(2)], where r is the radius of an ideal circle that intersects the elliptical fossa ovalis in its semi-latus rectum, c is the foci half-distance of the fossa ovalis, and p is its semi-latus rectum). During the procedure, the four-chamber plane allowed us to obtain easily interpretable images of all stages of device deployment. Midterm complete occlusion rate was 97.8%. No ICE-related complications occurred. CONCLUSIONS: The ICE evaluation of ASDs allows quantitative and qualitative information for both proper ASO selection and optimal device placement, thus eliminating the cumbersome balloon-sizing maneuver and the need for general anesthesia during TEE monitoring.

Adolescent↗

Thirty-year electrocardiographic follow-up after repair of tetralogy of Fallot or atrial septal defect.

BACKGROUND AND PURPOSE: Knowledge about long-term electrocardiographic changes after surgery for congenital heart disease is limited. METHODS: Eleven patients with corrected tetralogy of Fallot (ToF) and 14 with corrected atrial septal defect (ASD) were followed up at 20 and 30 years after surgery. RESULTS: Approximately 50% of the ASD group developed prolonged QRS duration. In the ToF group, 7 increased QRS duration by more than 20 milliseconds. Nearly all had right bundle-branch block, and 30% of them also had bifascicular block. Two in the ASD group developed first grade atrioventricular block. Five ASD and 6 ToF had prolonged corrected QT duration in the late postoperative phase. CONCLUSIONS: Even after primarily good results of surgery in congenital heart disease, unknown late effects may occur not only in complex lesions such as ToF but also after ASD correction. Regular medical checkups are important after surgical correction in congenital heart disease.

Adolescent↗

Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice.

Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.

Animals↗

A voxel-based investigation of brain structure in male adolescents with autistic spectrum disorder.

Autistic spectrum disorder (ASD) has been associated with abnormal neuroanatomy in many imaging and neuropathological studies. Both global brain volume differences and differences in the size of specific neural structures have been reported. Here, we report a voxel-based morphometric whole brain analysis, using a group specific template, on 16 individuals of normal intelligence with autistic spectrum disorder (ASD), and a group of 16 age-, sex- and IQ-matched controls. Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex. A local decrease in grey matter volume was found in the right thalamus. A decrease in global white matter volume in the ASD group did not reach significance. We found the increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution: 'theory of mind' (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus). The picture as a whole may reflect an abnormally functioning social cognitive neural network. We suggest that increased grey matter volume may play a pivotal role in the aetiology of the autistic syndrome.

Adolescent↗

Visual-auditory integration during speech imitation in autism.

Children with autistic spectrum disorder (ASD) may have poor audio-visual integration, possibly reflecting dysfunctional 'mirror neuron' systems which have been hypothesised to be at the core of the condition. In the present study, a computer program, utilizing speech synthesizer software and a 'virtual' head (Baldi), delivered speech stimuli for identification in auditory, visual or bimodal conditions. Children with ASD were poorer than controls at recognizing stimuli in the unimodal conditions, but once performance on this measure was controlled for, no group difference was found in the bimodal condition. A group of participants with ASD were also trained to develop their speech-reading ability. Training improved visual accuracy and this also improved the children's ability to utilize visual information in their processing of speech. Overall results were compared to predictions from mathematical models based on integration and non-integration, and were most consistent with the integration model. We conclude that, whilst they are less accurate in recognizing stimuli in the unimodal condition, children with ASD show normal integration of visual and auditory speech stimuli. Given that training in recognition of visual speech was effective, children with ASD may benefit from multi-modal approaches in imitative therapy and language training.

Adolescent↗

Frequency of EEG abnormalities in age-matched siblings of autistic children with abnormal sleep EEG patterns.

Epileptiform activity in sleep has been described even in the absence of clinical seizures in 43-68% of patients with autistic spectrum disorders (ASDs). Genetic factors may play a significant role in the frequency of epilepsy, yet the frequency in normal age-matched controls is unknown. We studied overnight ambulatory electroencephalograms (EEGs) in 12 nonepileptic, nonautistic children with a sibling with both ASDs and an abnormal EEG. EEG studies were read and described independently by two pediatric epileptologists; 10 were normal studies and 2 were abnormal. The occurrence of abnormal EEGs in our sample (16.6%) was lower than the reported occurrence in children with ASDs. Further, the two abnormal EEGs were of types typically found in childhood and were different from those found in the ASD-affected siblings. The lack of similarity between sibling EEGs suggests that genetic factors alone do not explain the higher frequency of EEG abnormalities reported in ASDs.

Autistic Disorder↗

Atrial septal defect resulting from mitral balloon valvuloplasty: relation of defect morphology to transseptal balloon catheter delivery.

Percutaneous balloon mitral valvuloplasty has been shown to be an effective means of reducing mitral valve gradient and increasing mitral valve area in patients with mitral stenosis. Most techniques currently employed for performing this procedure involve delivery of one or two balloon valvuloplasty catheters through the interatrial septum en route to the mitral valve orifice. To determine the morphology of the resultant atrial septal defect (ASD), particularly as a function of the technique employed, we performed a series of in vitro experiments designed to simulate a variety of technical approaches. Ninety-eight experiments in total were performed in 19 normal adult hearts obtained in the fresh, nonpreserved state at necropsy. Transseptal delivery and withdrawal of two conventional, elliptical balloon catheters through two, individual septostomy sites was found to produce the largest ASD (combined area of two defects = 21.4 +/- 2.2 mm2). The defect resulting from transseptal delivery and tandem withdrawal of two elliptical balloon catheters through a single septostomy site measured 14.8 +/- 1.1 mm2, significantly (p = 0.0043) smaller than that produced by two septostomies. Transseptal delivery and withdrawal of a single, segmentally inflating (Inoue) balloon catheter produced a defect of intermediate size (17.5 +/- 1.2 mm2). ASD size was exacerbated by improper balloon withdrawal compared with tandem withdrawal of two completely deflated balloon catheters. Simultaneous withdrawal of two completely deflated balloon catheters through the same septostomy site increased ASD size from 14.8 +/- 1.1 mm2 to 23.6 +/- 2.3 mm2 (p = 0.0004). Simultaneous withdrawal of two incompletely deflated balloon catheters further increased ASD size to 45.8 +/- 2.6 mm2 (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗

Pulmonary vascular disease in secundum atrial septal defect in childhood.

Pulmonary vascular structure was analyzed in the lungs of 10 patients with a secundum atrial septal defect (ASD) in whom pulmonary hypertension had developed. Four patients were aged 6 months or less, 5 were aged 2 to 9 years, and 1 was 21 years old. Pulmonary vascular structure was analyzed using lung biopsy tissue in 5 and autopsy material in the other 5. All the infants presented with heart failure and all had a marked increase in pulmonary arterial smooth muscle; only 1 infant survived surgery. Of the 5 older children, 1 presented with cyanosis, but in the rest the ASD was incidental to the presentation. Three patients had severe pulmonary vascular disease, similar to that seen in adults with a hypertensive ASD. Only 2 older children underwent successful surgery. In 1 child and in the 1 adult, the severity of the pulmonary vascular disease precluded surgery. The ASD was closed in 8 patients, but only 3 survived. Pulmonary hypertension develops rarely in secundum ASD in childhood.

Adolescent↗

Role of inverted buttoned device in transcatheter occlusion of atrial septal defects or patent foramen ovale with right-to-left shunting associated with previously operated complex congenital cardiac anomalies.

Feasibility, safety, and effectiveness of transcatheter occlusion of atrial septal defect (ASD) with the buttoned device has been demonstrated. Despite its effectiveness in occluding secundum ASD with left-to-right shunt and patent foramina ovalia, presumably responsible for paradoxic embolism, it has limitations in effectively occluding ASD with evident right-to-left shunts. Therefore, the device was modified so that the square-shaped occluder component of the device is on the right atrial side, the inverted buttoned device. This study determines the feasibility, safety, and effectiveness of inverted buttoned device occlusion of atrial defects with right-to-left shunts. During a 17-month period ending August 1996, 12 patients, aged 1.6 to 39.0 years, underwent occlusion of residual ASD after repair of pulmonary atresia/stenosis with intact ventricular septum (n = 5), modified or fenestrated Fontan for tricuspid or pulmonary atresia (n = 5), and double-inlet left ventricle (n = 2). The systemic arterial oxygen saturation increased (p <0.001) from 82 +/- 7% (range 72% to 90%) to 94 +/- 3% (range 88% to 98%). There was no change in heart rate or cardiac index measured by Fick. Right atrial pressure increased by 1 to 4 mm in 5 of 12 patients (42%). There was trivial (n = 5) or no (n = 7) residual shunt by color Doppler study. Six- to 18-month (median 12) follow-up in all 12 patients revealed stable oxygen saturations (92 +/- 3%) by pulse oximetry. Color Doppler studies revealed small (n = 1), trivial (n = 1), or no (n = 10) residual shunt at follow-up. Based on these data, it is concluded that transcatheter occlusion of ASD with right-to-left shunts with inverted buttoned device is feasible in relieving arterial hypoxemia. Further clinical trials in a larger number of patients and careful evaluation of follow-up results are indicated to examine its safety and longer term effectiveness.

Adolescent↗

Concomitant mitral valve or atrial septal defect surgery and the modified Cox-maze procedure.

Atrial fibrillation (AF) is generally associated with rheumatic valve disease and atrial septal defects (ASD) in young adults. Surgical correction of both disorders fails to convert to sinus rhythm or prevent further episodes of paroxysmal or chronic AF in most patients. The role and efficacy of combining mitral valve surgery or ASD correction with AF surgery in this setting has not been widely addressed and remains to be established. The present study prospectively assessed the recovery of sinus rhythm, functional status, and atrial function in 21 patients (mean age 42 +/- 9.2 years) who underwent a modified Cox-maze procedure concomitant with mitral valve or ASD surgery at our institution between March 1993 and February 1995. Seventeen (81%) had chronic AF, and 4 (19%) had paroxysmal AF, with a mean AF duration of 3.5 +/- 3.6 years (range 0.6 to 15.3). Concomitant surgery was performed in 9 patients (42.9%) with mitral stenosis, 5 (23.8%) with mitral regurgitation, 1 (4.8%) with mitral and aortic regurgitation, and 3 (14.3%) with ASD. Eighteen patients (86%) were in New York Heart Association class II to IV before operation. Doppler echocardiography was performed in all patients before surgery, and 1 week, and 3 and 6 months after surgery in patients maintaining sinus rhythm. One patient with severe mitral stenosis and depressed ventricular function died in the immediate postoperative period. Sinus rhythm was restored in the immediate postoperative period in 7 patients (35%), and in another 10 patients (50%) before discharge (mean 5.8 +/- 2 days). Overall, sinus rhythm was restored before discharge in 17 patients (85%); 3 (15%) patients required antiarrhythmic therapy. Doppler echocardiography performed 3 months after surgery documented atrial contractility (A and E waves) in 12 patients (71%). After a mean follow-up period of 8 months (range 3 to 23), 18 (90%) remained in sinus rhythm. Sinus rhythm was successfully restored and maintained in most patients with drug refractory AF undergoing a concomitant Cox-maze procedure with mitral valve or ASD surgery improving atrial function and New York Heart Association class.

Adult↗

Echocardiographic characteristics of successful deployment of the Das AngelWings atrial septal defect closure device: initial multicenter experience in the United States.

The AngelWings device is a newer transcatheter device used for closure of secundum atrial septal defects (ASD) and patent foramen ovale (PFO), which consists of a self-centering, 2-disk system. Transesophageal echocardiography (TEE) plays a pivotal role in the deployment of the 2 disks of this device, on the appropriate sides of the atrial septum. The objective of this study is to describe the echocardiographic findings associated with successful deployment of the AngelWings device for closure of ASD and PFO. We evaluated the TEE studies of 70 patients enrolled in 4 United States centers, for closure of ASD and PFO with the AngelWings device. The TEE characteristics of successful and unsuccessful deployments were analyzed. Residual shunts across the atrial septum were assessed by TEE at the end of the procedure, 24 hours later by transthoracic echocardiography, and at 6 months by TEE. The deployment of the device was successful in 65 patients (93%). In the unsuccessful group, ASD size by TEE was larger (13.4 +/- 3.1 vs 8.9 +/- 4.7 mm, p <0.05). TEE was successful in identifying snagging of the device by intracardiac structures and prolapse of corners of the left or right atrial disk through the ASD, features that were difficult to identify by fluoroscopy. The echocardiographic characteristics outlined here are important guidelines for successful deployment of the AngelWings device.

Adolescent↗

Improvement in noninvasive electrophysiologic findings in children after transcatheter atrial septal defect closure.

To evaluate whether transcatheter closure of secundum atrial septal defects (ASD) affected noninvasive electrophysiologic variables in children, we reviewed the pre-procedural and 1-year postprocedural electrocardiograms and Holter recordings of 18 consecutive children referred for ASD closure. Patients included in the study were a mean of 5.0 years old (SD 1.1) and weighed a mean of 17.9 kg (SD 4.1). ASDs had a mean diameter of 14.0 mm (SD 2.4) and average shunt ratio (pulmonary-to-systemic flow) of 2.1:1. One year after occluder device placement, 9 children (50%) had detectable residual shunts by transthoracic echocardiograms, but only 2 (11%) had shunts that were felt to be possibly significant. One or more fractured occluder legs were noted by chest roentgenogram in 15 patients (83%). Electrocardiograms at follow-up demonstrated improvement in right ventricular dilation in 4 of 7 patients, right atrial enlargement in 3 of 4 patients, and 1 degree atrioventricular block in 2 of 3 patients. Holter recordings showed a decreased incidence of accelerated atrial rhythm in 3 of 7 patients, prolonged junctional escape rhythm in 2 of 2 patients, and premature atrial contractions in 2 of 2 patients. No finding correlated with patient age, defect or occluder diameter, occluder leg fracture(s), or residual defects. These improvements in electrophysiologic abnormalities compare favorably with changes seen 1 year after surgical closure. In conclusion, placement of a transcatheter ASD device in children diminishes noninvasive electrophysiologic abnormalities at 1-year follow-up. By relieving hemodynamic stress caused by an ASD in childhood, a transcatheter device may prevent arrhythmia disturbance later in life.

Cardiac Catheterization↗

A new instrument for surgical creation of an atrial septal defect.

An instrument for surgical creation of an atrial septal defect (ASD) was designed and tested in puppies weighing an average of 4.7 kg. Oxygen saturations were obtained in both atria, the superior vena cava, and the inferior vena cava before and after septectomy. The instrument has a cutting cylinder introduced into the right atrium (RA) through the right atrial appendage with a second part (base-plate) inserted into the left atrium (LA) just posterior to the interatrial groove. In 21 animals (Group 1), a single hole was created in dogs killed 48 hours later. In 9 animals (Group 2), an attempt was made to create two adjoining holes. In 14 animals (Group 3), a single hole was created and the dogs were allowed to triple their body weight before they were killed. Group 1 dogs demonstrated a 10% increase in average venae cavae--RA oxygen saturation immediately after septectomy and a 9.4 +/- 0.37 mm diameter of the ASD at death; in Group 2, there was a 14% average step-up and a 12.7 +/- 0.6 mm diameter of the ASD; and in Group 3, the diameter of the ASD was 11.5 +/- 0.4 mm, representing a 50% increase in average area with dog growth compared with that of Group 1. After this experience in the production of ASDs in 44 experimental animals, we find that this instrument seems to be reliable, simple, and safe.

Animals↗

Studies of the vicarious traumatization of college students by the September 11th attacks: effects of proximity, exposure and connectedness.

From mid-October 2001 through the end of November 2001, we collected fairly large sets of questionnaires from undergraduates at three public universities (Albany, NY, n = 507, Augusta, GA, n = 336, Fargo, ND, n = 526 ) to assess rate of acute stress disorder (ASD) and level of ASD symptoms following the September 11th attacks, rate of current posttraumatic stress disorder (PTSD) and level of PTSD symptoms, and current level of depressive symptoms resulting from the September 11th attacks. We also gathered information on exposure to media coverage of the attacks, connectedness to the World Trade Center (WTC) and personnel there, and degree of engagement in reparative acts such as giving blood, attending vigils. We found higher levels of ASD, ASD symptoms, PTSD and PTSD symptoms as a function of geographical proximity to New York City (and within the Albany site, proximity of students' homes) and gender. Exposure (hours of TV watched) was a predictor in some instances as was connectedness to WTC victims. ASD symptoms were the strongest predictor of subsequent PTSD symptoms. Path models accounted for over 60% of the variance in PTSD symptoms.

Acute Disease↗

Acute stress disorder in youth: a multivariate prediction model.

There is little empirical support for the diagnosis of acute stress disorder (ASD) in children and adolescents. Most reports treat ASD as "provisional posttraumatic stress disorder (PTSD)" (meaning that children evidence ASD on the way to a formal diagnosis of PTSD), while speculating on factors that might moderate or mediate the transformation of ASD into PTSD. This report briefly reviews the literature on ASD in the context of presenting a testable, multivariate model for understanding acute stress responses in youth.

Adolescent↗