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PubMed2007

Brief report: a scale for rating conversational impairment in autism spectrum disorder.

There are few well-standardized measures of conversational breakdown in Autism Spectrum Disorders (ASD). The study's objective was to develop a scale for measuring pragmatic impairments in conversations of individuals with ASD. We analyzed 46 semi-structured conversations of children and adolescents with high-functioning ASD using a functional linguistic paradigm. Five constructs were developed that assessed difficulties related to the pragmatics of conversation: atypical intonation; semantic drift; terseness; pedantic speech; perseveration. The scale shows good inter-rater reliability and variation in the scales is not simply a reflection of IQ or language competence. This tool represents a way of characterizing language use in ASD and is an initial step towards developing a tool to evaluate change in degree of social impairments in conversation.

Adolescent↗
PubMed2006

Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion).

The extent to which the phenotype of children comorbid for velocardiofacial syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic criteria for autism based upon the ADI-R. These eight plus an additional nine participants met diagnostic criteria for an autistic spectrum disorder (VCFS + ASD). Ninety-four percent of the children with VCFS + ASD had a co-occurring psychiatric disorder while 60% of children with VCFS had a psychiatric disorder. Children with VCFS + ASD had larger right amygdala volumes. All other neuroanatomic regions of interest were statistically similar between the two groups.

Adaptation, Psychological↗
PubMed2007

Stereotyped motor behaviors associated with autism in high-risk infants: a pilot videotape analysis of a sibling sample.

This study examined motor behaviors in a longitudinal cohort of infant siblings of children with autism. Stereotypic movements and postures occurring during standardized observational assessments at 12 and 18 months were coded from videotapes. Participants included eight infant siblings later diagnosed with autism spectrum disorder (ASD), a random sample of nine non-diagnosed siblings, and 15 controls. Videos were coded blind to diagnostic group. At 12 and 18 months the ASD group "arm waved" more frequently and at 18 months, one posture ("hands to ears") was more frequently observed in the ASD and non-diagnosed group compared to the controls. Overall, the siblings subsequently diagnosed with ASD and the comparison groups had considerable overlap in their repertoires of stereotyped behaviors.

Autistic Disorder↗
PubMed2007

Predictors of optimal outcome in toddlers diagnosed with autism spectrum disorders.

A diagnosis of autism spectrum disorder (ASD) is usually taken to be permanent. In this study, 13 two-year-old children with ASD lost the diagnosis by age 4, at which time they scored within the normal range on standardized measures of cognitive and adaptive functioning. No differences were found in symptom severity, socialization, or communication between children who lost the ASD diagnosis and children who did not, but children with PDD-NOS were significantly more likely than those with full autistic disorder to move off the spectrum. The clearest distinguishing factor was motor skills at age 2. Results support the idea that some toddlers with ASD can lose their diagnosis and suggest that this is difficult to predict.

Activities of Daily Living↗
PubMed2026

Untargeted metabolomics and proteomics reveals cocoa-mediated mitigation of valproic acid-induced dysregulation in a zebrafish model of autism: pilot study.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by behavioral impairments and limited therapeutic options. Emerging evidence suggests that plant-derived polyphenols may offer neuroprotective benefits. OBJECTIVES: This pilot study aimed to investigate the therapeutic potential of polyphenol-rich cocoa extract in a valproic acid (VPA)-induced zebrafish model of ASD. METHODS: Zebrafish were exposed to 3 μM VPA, cocoa powder providing 2.5 μM (-)-epicatechin, a combination of both, or left untreated. Behavioral phenotyping was conducted using DanioVision and gut morphology was assessed. Untargeted metabolomic and proteomic profiling was performed followed by univariate and multivariate analyses. RESULTS: VPA exposure induced ASD-like behavioral hyperactivity, and severe gastrointestinal abnormalities. Cocoa co-treatment ameliorated both behavioral performance and gut architecture. Metabolomic profiling revealed VPA-associated disruptions in neurotransmission, methylation, mitochondrial function and redox homeostasis. Proteomic profiling showed elevated levels of trafficking protein particle complex subunit 11, proteasomal ubiquitin receptor, betaine-homocysteine S-methyltransferase 1 (BHMT-1), and desmoplakin-A, consistent with genotoxic stress and impaired protein trafficking. Cocoa co-treatment normalized BHMT-1 and desmoplakin-A expression and mitigated broader metabolic dysregulation. CONCLUSION: Collectively, these results suggest that polyphenol-rich cocoa may represent a promising multi-targeted nutraceutical approach for mitigating ASD-related neurodevelopmental and metabolic disturbances.

Animals↗
PubMed2004

Early Diagnosis of Autism Spectrum Disorders.

Autistic spectrum disorders (ASD) are an often-disabling continuum of disorders affecting two to four in 1000 children. These disorders have a core set of defining features including impaired verbal and nonverbal communication, impaired social interaction, and restricted or repetitive patterns of behavior. The cause of autism is unclear. The disorder can be defined only by related behaviors. Although there has been considerable improvement in standardized screening techniques for ASD in the past 10 years, screening and diagnostic practices in medicine and education lag far behind clinical research. Various studies have found the average age of diagnosis to be between 3 and 6 years, with significant differences as a function of ethnicity and socio-economic status. Preliminary research suggests that in some populations, missed diagnosis and misdiagnosis of ASD are common. This may be caused partly by inadequate screening practices. It also may reflect that presentation of symptoms varies from patient to patient. Lack of resources for appropriate referral, diagnosis, and treatment may play an important role. This article discusses recent progress in ASD screening, what is known of current screening and diagnostic practices, and future directions for research and practice improvement. The best practice model for the screening and early diagnosis of autism spectrum disorders and other developmental disabilities should include routine developmental surveillance as part of well-child pediatric care. General developmental screening should be followed by autism-specific screening for those children who fail the initial developmental screen, or whose parents report suspect behaviors.

Journal Article↗
PubMed1994

Thermodilution left-sided cardiac output for valve area determination after balloon mitral valvotomy.

This study was conducted to establish the validity of left-sided cardiac output measurement with a Swan-Ganz catheter and assess its accuracy in estimating mitral valve area (MVA) by the Gorlin formula. The use of right-sided cardiac output after balloon mitral valvotomy (BMV) can give inaccurate measurements for Gorlin-derived MVA because of the atrial septal defect (ASD) created during the procedure. The left-sided cardiac output was measured with a Swan-Ganz catheter (proximal port in the left atrium and then in the left ventricle, and distal port in the ascending aorta) in 10 consecutive patients before and after BMV. Gorlin-derived MVA cardiac output by this method was compared with (1) Gorlin-derived MVA by means of right-sided cardiac output with and without balloon occlusion of the ASD and (2) MVA measured by echocardiography. Before BMV, a close agreement with a good correlation between left-sided and right-sided cardiac output was found (r = 0.83, p = 0.006). Furthermore, Gorlin-derived MVA by cardiac output with either method was comparable with valve area by echo. After BMV, left-sided cardiac output correlated well (r = 0.92, p = 0.0002) and was comparable with right-sided cardiac output with occlusion of the ASD (mean difference 0.17 +/- 0.49 L/min, p = 0.3) but was significantly lower than the value obtained with open ASD (mean difference 0.93 +/- 0.77 L/min, p = 0.004). Comparison of the correspondent MVAs yielded similar results. Gorlin-derived MVA with left-sided cardiac output and MVA by echo were also similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗
PubMed1989

Comparison of cardiovascular adjustments to exercise in adolescents 8 to 15 years of age after correction of tetralogy of fallot, ventricular septal defect or atrial septal defect.

Surgical correction of tetralogy of Fallot (TF) has generally been associated with a reduced maximal exercise tolerance, possibly related to the ventriculotomy inherent to the intracardiac repair procedure. This study documents the exercise hemodynamics of a group of patients operated on for TF who showed similar clinical and functional characteristics, and compares these responses to those of age-matched patients operated on for an isolated ventricular septal defect (VSD) or atrial septal defect (ASD) in an attempt to better understand the role of the ventriculotomy in the exercise limitation. Thirty patients, ages 12 to 19 years, operated on before 5 years of age for complete repair of TF (n = 13), VSD (n = 7) or ASD (n = 10) and 10 age-matched control subjects underwent a progressive maximal cycling test to determine the maximal oxygen uptake (VO2 max), and completed submaximal cycling at intensities of 33 and 66% VO2 max, respectively, to determine the cardiac output (CO2-rebreathing). No significant differences in VO2 max were observed (TF = 37.6 +/- 10; VDS = 34.0 +/- 9.2; ASD = 36.5 +/- 7; controls = 41.3 +/- 6.0 ml/kg/min). The maximal heart rate, however, remained lower in all patient groups in comparison with control subjects (p less than or equal to 0.05) (TF = 178 +/- 14; VSD = 172 +/- 17; ASD = 179 +/- 16; controls = 191 +/- 12 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Transcatheter closure of atrial septal defect by "buttoned" devices.

During a 21-month period ending in August 1991, 12 patients underwent transcatheter closure of atrial septal defect (ASD) with a "buttoned" device through an 8Fr sheath, using an institutional review board-approved, custom-made device protocol initially, and Food and Drug Administration-approved clinical trials subsequently. Ten children had left-to-right shunts across the ASD and 2 adults had their patent foramen ovale closed to prevent recurrent paradoxical embolism (including cerebrovascular accidents). The device dislodged in 1 of the 4 patients in whom a first-generation device was used, and retrieval of the device, and surgical closure of the ASD were performed without incident. In the remaining 11 patients (age range 7 months to 45 years, weight 3.6 to 64 kg), the device remained intact, and pulmonary-to-systemic flow ratio decreased from 2.1 +/- 0.3 to 1.04 +/- 0.06. Follow-up chest x-ray and echo-Doppler studies were available in all patients 0.5 to 18 months after the procedure. The device was intact in all patients. Small residual shunt detected by color Doppler was seen in 2 children. Right ventricular size decreased (23 +/- 6 to 17 +/- 3 mm; p less than 0.01), and paradoxical septal motion disappeared in all patients. There was no recurrence of paradoxical embolism in the 2 adults. No complications occurred during follow-up. It is concluded that transcatheter closure of ASD with the buttoned device is feasible, effective and safe, and can be accomplished with small, 8Fr sheaths (even in infants weighing 3.6 kg), follow-up results are excellent, and clinical trials on a larger number of patients are needed.

Adolescent↗
PubMed1993

Long-term follow-up (9 to 20 years) after surgical closure of atrial septal defect at a young age.

To assess the long-term cardiac status after surgical closure of an atrial septal defect (ASD) at a young age, 104 of 135 children who consecutively underwent surgery (aged 0 to 14 years) at 1 institution between 1968 and 1980 participated in a follow-up study and underwent a complete cardiologic examination. Mean follow-up was 14.5 +/- 2.8 years. Most patients (87%) believed their health to be good or very good. At physical examination, all patients were in good health. Ninety-three patients (89%) were in sinus rhythm. Echocardiography showed that right ventricular dilatation was present in 27 patients (26%), 2 of whom had a residual ASD. Bicycle ergometry revealed that 88 patients (88%) had a normal exercise capacity. Both supraventricular and ventricular arrhythmias were observed in 67% of patients by 24-hour ambulatory electrocardiography, but only 3 (3%) had received antiarrhythmic medication, and 4 (4%) had needed a pacemaker. In the group of patients with right ventricular dilatation, the exercise capacity and prevalence of arrhythmias did not differ significantly from those in the group with a normal sized right ventricule. The outcome in patients with a secundum-type ASD was not different from that of those with a sinus venosus-type ASD. The finding of anatomic, functional or electrophysiologic abnormalities was not associated with a longer duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1977

Automatic detection and localization of epileptic foci.

A new method of automatic EEG analysis (ASD or automatic non-stationarity detection) derived from a parametric EEG model (autoregressive filter model) and based on inverse filtering, has been applied to scalp and subdural EEGs of epileptic patients. By this method it was possible to detect the occurrence of transient non-stationarities such as paroxysmal patterns of activity (spikes, spike-and-waves) characteristic of inter-ictal EEGs. The ASD has been implemented in a general purpose digital computer. The method allows: (a) statistical evaluation of paroxysmal patterns; (b) multi-channel analysis, where the interrelationships of different derivations are quantified and displayed by means of a clinically useful spatial map. The application of the ASD method to scalp and subdural EEGs, simultaneously recorded, has revealed that a number of transient non-stationarities detected in the scalp by the program yet not by visual inspection, coincide with clear paroxysmal patterns in subdural derivations. In this way conventional definitions of characteristic paroxysmal patterns at the scalp are put in question. Identical conclusions regarding the localization of an epileptogenic zone in 4 patients were obtained either using the conventional methods of recording electro-clinical seizures in EEGs of long duration or applying the ASD method to short EEG epochs (100 sec long, at most).

Computers↗
PubMed1996

[Fatal infectious complications in 2 patients with adult onset Still disease].

If adult Still's disease (ASD) can sometimes lead to severe destructive joint lesions and to various systemic manifestations, life-threatening complications are very rare. However, a long-term and high-dose corticosteroid therapy is often required to control the disease, with frequent corticodependence. Some authors have proposed methotrexate as a second line drug for ASD, that could permit a corticosteroid sparing effect. We report two cases of acute fatal infectious complications--legionella pneumonitis and multiple brain abscess caused by Nocardia asteroides--in two patients treated for ASD with both corticosteroids and methotrexate. These two cases raise the problem of the immunodepression induced by this combination therapy and point out the difficulties in aggressive forms of ASD.

Adult↗
PubMed2006

Immediate and late outcomes of patients undergoing transseptal left-sided heart catheterization for symptomatic valvular and arrhythmic diseases.

BACKGROUND: The transseptal technique has been widely used for diagnostic and therapeutic left-sided heart catheterization. However, its differential immediate and late outcomes among patients with various valvular and arrhythmic diseases are not yet determined. METHODS: Beginning from 1993, all patients undergoing transseptal procedures were screened and categorized into diagnosis, arrhythmia, and valvuloplasty groups according to the purposes of the catheterization. Incidences of transseptum-related acute major events (cardiac perforation, embolic stroke, and bradyarrhythmia during the procedure) and late complications (residual atrial septal defect [ASD], embolic stroke, bradyarrhythmia, and death up to 18 months) were analyzed and compared between groups. RESULTS: From January 1993 to May 2003, a total of 176 patients underwent 184 transseptal procedures for diagnosis of valvular heart diseases (n = 8), catheter ablation of arrhythmogenic foci (n = 29), and mitral valvuloplasty (n = 147). The immediate outcome was similar among the 3 groups, with an overall acute complication incidence of 3.8%. At follow-up, the incidences of bradyarrhythmia, embolic stroke, and death were not different among the 3 groups. Patients undergoing valvuloplasty had a significantly higher prevalence of residual ASD, especially for those with more severe mitral stenosis and less valvuloplasty success. However, presence of ASD did not impose disadvantage over the 1.5-year prognosis. CONCLUSION: Transseptal left-sided heart catheterization can be safely applied to patients with different categories of cardiac diseases with comparably good immediate and late outcomes. Although patients undergoing percutaneous valvuloplasty have a higher chance of permanent ASD creation, their prognosis is not influenced.

Adolescent↗
PubMed2004

Evidence of adverse ventricular interdependence in patients with atrial septal defects.

Right ventricular (RV) volume overload is associated with left ventricular (LV) distortion and dysfunction. The availability of transcatheter device closure of secundum atrial septal defect (ASD) provides an ideal model for investigating the immediate effects of elimination of RV volume overload and avoiding the confounding effects of surgery on LV function. Echocardiograms before and after device closure of ASD were analyzed for ejection fraction, percent changes in cross-sectional area and circumference, percent changes in free wall and septal endocardial lengths, and eccentricity. We enrolled 34 patients (median age 9 years) who underwent device closure of ASD (pulmonary to systemic shunt 1.6 +/- 0.4). Ejection fraction and LV end-diastolic volume, reflective of chamber preload, were significantly decreased in the presence of RV volume overload and normalized after defect closure with normalization of LV shape. Altered LV geometry secondary to RV volume overload was associated with regional variation in preload,such that diastolic circumference, a surrogate of myofiber preload, increased after closure of ASD secondary to a small increase in LV free wall arc length in conjunction with a much more significant increase in septal length. Thus, LV dysfunction associated with RV volume overload is secondary to altered chamber geometry and decreased myofiber preload. This physiology is immediately reversible and is independent of heart rate and afterload.

Child↗
PubMed2004

Surgical patch closure of atrial septal defects.

BACKGROUND: Development of nonsurgical techniques for closure of atrial septal defects (ASD) has prompted reevaluation of current surgical outcomes with an emphasis on less invasive methods. METHODS: This retrospective review is based on a single surgeon's experience between July 1, 1988 and December 21, 2002 with 176 consecutive adult (n = 47) and pediatric (n = 129) surgeries, in which ASD was the primary anatomical diagnosis to ascertain current optimal methods and outcomes expected for surgical closure. Patch closure with pericardium was used in all cases. Surgical methods encompassed three phases. The first phase was defined by traditional sternotomy; the second phase involved a series of technical modifications to shorten incisions and reduce surgical trauma; the third phase consisted of standardized less invasive techniques based upon age and gender with "bikini line" incisions for adult females, limited median sternotomy for adult males, and mini-median sternotomy for children. All patients underwent echocardiography to assess ASD closure. RESULTS: There were no deaths. The most frequent perioperative complications were atrial fibrillation (adult 10%, pediatric 1.2%) and post pericardiotomy syndrome (adult 2%, pediatric 4.7%). All patients had secure and complete closure of ASDs with no residual shunts (trivial or otherwise) documented by echocardiography. No less invasive procedures required conversion. CONCLUSIONS: Surgical technique evolved from standard sternotomy to limited access incisions using modified cannulation techniques and incision locations determined by age and gender of the patient without deterioration in outcome quality. Both standard and less invasive surgical methods can achieve secure closure of the septum with biological patches, which are incorporated into the tissue structure of the heart and which are free from materials-related failure modes. Patient satisfaction is enhanced by utilizing the least invasive, least traumatic, and most cosmetically appealing techniques for access and cardiopulmonary bypass.

Adolescent↗
PubMed2006

High functioning children with autism spectrum disorder: a novel test of multitasking.

High functioning children with a diagnosis of autism or Asperger's syndrome (HF-ASD) often experience difficulties organising goal-directed actions in their day-to-day lives, requiring support to schedule daily activities. This study aimed to capture these everyday difficulties experimentally using multitasking, a methodology that taps into the cognitive processes necessary for successful goal-directed activities in everyday life. We investigated multitasking in children with HF-ASD using a novel multitask test, the Battersea Multitask Paradigm. Thirty boys participated in the study, 14 with HF-ASD and 16 typically developing controls, matched for age and IQ. Group differences in multitasking were observed. Participants with HF-ASD were less efficient at planning, attempted fewer tasks, switched inflexibly between tasks and broke performance rules more frequently than controls.

Autistic Disorder↗
PubMed2006

Attributing social and physical meaning to ambiguous visual displays in individuals with higher-functioning autism spectrum disorders.

The weak central coherence (WCC) account of autism characterizes the learning style of individuals with this condition as favoring localized and fragmented (to the detriment of global and integrative) processing of information. This pattern of learning is thought to lead to deficits in aspects of perception (e.g., face processing), cognition, and communication (e.g., focus on disjointed details rather than "gist" or context), ultimately leading to social impairments. This study was carried out to examine whether WCC applies to social and to non-social aspects of learning alike, or, alternatively, some areas of learning (e.g., physical reasoning) are spared in autism. classic social animation as quantified in the Social Attribution Task (SAT) () and a novel animation involving physical reasoning (the Physical Attribution Task; PAT) were used to test the domain specificity of the WCC hypothesis. A pilot study involving a reference group of typically developing young adults and a group of individuals with higher-functioning autism spectrum disorders (ASDs) revealed gender differences in the reference group in regards to performance on the PAT (males outperformed females). In a follow-up case-control comparison involving only males where the ASD group was matched on age and IQ to a typically developing (TD) group of children, adolescents, and adults, the ASD group showed lower SAT scores and comparable PAT scores relative to the TD group. The interaction of diagnostic group by task was highly significant, with little overlap between the groups in the distributions of SAT minus PAT scores. These results indicated preserved integrative skills in the area of physical attribution in the ASD group, thus failing to support the WCC account as a domain-independent (or more general) model of learning in autism, while highlighting the centrality of the social deficits in the characterization of learning style in the autism spectrum disorders.

Adolescent↗
PubMed2006

Histological and magnetic resonance imaging assessment of cortical layering and thickness in autism spectrum disorders.

BACKGROUND: Qualitative reports of the cerebral cortex in a small number of autism spectrum disorder (ASD) cases have suggested an increase in thickness and disruptions in migration and lamination patterns. METHODS: We examined postmortem ASD individuals and age-matched controls using magnetic resonance imaging (MRI) to evaluate total cortical thickness, and histological samples to evaluate the pattern of cortical layering. RESULTS: Overall, thickness measures from ASD subjects were equivalent to control cases. Individual regions showed marginal but nonsignificant thickness differences in the temporal lobes. Cortical thickness values in ASD subjects decreased significantly with age. Quantitative examination of proportional layer thickness in histological sections indicated that the pattern of cortical layering was largely undisturbed, while qualitative examination of these same samples revealed evidence of cell clustering and supernumerary cells in layer I and the subplate. These features were not severe and were never found in a majority of cases. CONCLUSIONS: These findings support limited disturbances in cortical cell patterning, but do not indicate a major deficit in the orderly migration of cortical neuroblasts during development, or their subsequent aggregation into the laminar pattern found in typically developing individuals.

Adolescent↗