Facial expression recognition and emotion understanding in children after neonatal open-heart surgery for transposition of the great arteries.

AIM: Theory of mind impairments are part of the cognitive morbidities associated with transposition of the great arteries (TGA). We sought to assess core components of social cognition in school-aged children with TGA. METHOD: Thirty-eight children with neonatal corrected TGA (27 males, 11 females; mean age 7y 3mo, SD 1y 2mo) and a comparison group (n=31; 24 males, 7 females; mean age 7y 4mo, SD 1y 1mo) participated in this study. All children completed measures of facial expression recognition, emotion comprehension, and second-order cognitive and affective false-belief tasks. The association of medical pre-, intra-, and postoperative variables with cognitive outcomes was explored. RESULTS: After controlling for potential covariates, children with TGA performed significantly less accurately in the mental category of the emotion comprehension battery (p=0.002) and on second-order affective false-belief tasks (p<0.05). Preoperative variables including an associated ventricular septal defect (p=0.02), a younger age at open-heart surgery (p=0.03), and a prenatal diagnosis of TGA (p=0.02) were significantly associated with better outcomes. INTERPRETATION: School-aged children with TGA display significant impairment on complex affective mental state understanding even though facial expression recognition was generally preserved. Preoperative factors may be important determinants for long-term outcomes after cyanotic congenital heart disease.

Use of early remedial services in children with transposition of the great arteries.

OBJECTIVES: To characterize the prevalence of use of early remedial services and its associated demographic, medical, and cognitive factors in children aged 4-6 years with corrected transposition of the great arteries (TGA). STUDY DESIGN: This was a prospective study of neurocognitive outcomes after TGA. Children underwent formal neuropsychological testing including general intelligence and a comprehensive battery of executive functions (EF) including motor and interference control, short-term memory, and working memory as well as cognitive flexibility. Parental reports on the children's behavior and EF were also evaluated. Demographic factors and preoperative, intraoperative, and postoperative factors as well as cognitive factors were examined according to the current use of remediation. RESULTS: Forty-five patients (67% male) and their parents participated in this study. Twenty-four (53%) patients were receiving remedial services. Male sex, a postnatal diagnosis of TGA, and a longer postoperative intensive care unit stay were significantly associated with use of remediation. Children receiving remediation had lower EF scores, had more severe EF deficits as observed by formal testing, and were rated as having more behavioral daily life difficulties. However, in the group without remediation, 13 children (43%) also displayed EF deficits rated as moderate to severe. CONCLUSIONS: Demographic and medical factors could help identify children at higher risk for neurocognitive delays. Evaluation of executive functioning from an early age may influence referral for remediation.

Impact of prenatal diagnosis on neurocognitive outcomes in children with transposition of the great arteries.

OBJECTIVES: To assess the effect of prenatal diagnosis of congenital heart disease on neurocognitive outcomes in children with d-transposition of the great arteries (TGA) after surgical correction. STUDY DESIGN: A prospective study of children born with a TGA between 2003 and 2005 and aged 4 to 6 years was conducted. General intelligence, language, executive functions, and social cognition scores and preoperative, intraoperative, and postoperative factors were evaluated according to time of TGA diagnosis. Neurocognitive data were also compared with a control group. RESULTS: Forty-five eligible patients (67% male) were examined; 29 had a prenatal diagnosis of TGA and 16 did not. All children were comparable in age, sex, and demographic variables. Diagnostic groups did not differ in preoperative, intraoperative, and postoperative variables. Preoperative acidosis was more frequent in the postnatal group (18% versus 3%). All patients had normal IQ scores, language, and verbal working memory. However, neurocognitive deficits were more prevalent and more severe in children with a postnatal-TGA. Prenatal diagnosis was associated with better outcomes in executive functions. CONCLUSIONS: Prenatal diagnosis of TGA is associated with better neurocognitive outcomes. Time of diagnosis may influence the development of early complex cognitive skills such as executive functions.

Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1.

AIM: To investigate the psychiatric and cognitive phenotype in young individuals with the childhood form of myotonic dystrophy type 1 (DM1). METHOD: Twenty-eight individuals (15 females, 13 males) with childhood DM1 (mean age 17y, SD 4.6, range 7-24y) were assessed using standardized instruments and cognitive testing of general intelligence, visual attention, and visual-spatial construction abilities. RESULTS: Nineteen patients had repeated a school grade. The mean (SD) Full-scale IQ was 73.6 (17.5) and mean Verbal IQ was significantly higher than the mean Performance IQ: 80.2 (19.22) versus 72.95 (15.58), p=0.01. Fifteen patients had one or more diagnoses on the DSM-IV axis 1, including internalizing disorders (phobia, n=7; mood disorder, n=6; other anxiety disorders, n=5) and attention-deficit-hyperactivity disorder, inattentive subtype (n=8). Twelve out of 22 patients had alexithymia (inability to express feelings with words and to recognize and share emotional states). Cognitive testing found severe impairments in visual attention and visual-spatial construction abilities in four out of 18, and 14 out of 24 patients respectively. No diagnosis was correlated with the transmitting parent's sex or with cytosine-thymine-guanine (CTG) repeat numbers. Patients with severe visual-spatial construction disabilities had a significantly longer CTG expansion size than those with normal visual-spatial abilities (p=0.04). INTERPRETATION: Children and adolescents with childhood DM1 have frequent diagnoses on DSM-IV axis 1, with internalizing disorders being the most common type of disorder. They also have borderline low intelligence and frequent impairments in attention and visual-spatial construction abilities.

A validated WAIS-IV short-form to estimate intellectual functioning in myotonic dystrophy type 1.

Currently, no rapid and specific instrument is available to briefly estimate intelligence in patients with myotonic dystrophy type 1 (DM1), a multisystemic disease that involves the CNS and is associated with cognitive deficits and low intellectual functioning. This study aimed to develop a DM1-specific and valid short-form of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) to estimate intellectual functioning in this population. Thirty non-congenital DM1 patients (10 female; mean age=46.77; SD= 9.76) were assessed with the WAIS-IV. Data were analyzed following two independent strategies: A) multiple linear regression with the aim of maintaining the scale's factorial structure; and B) correlational analyses between scores on all WAIS-IV subtests and Full-Scale IQ (FSIQ). Validity of the resulting short-forms was also analyzed. Three short-forms were developed: Proposal A from strategy A (Vocabulary, Block Design, Arithmetic and Symbol Search), Proposal B1 (Vocabulary, Block Design, Digit Span and Visual Puzzles) and Proposal B2 (Vocabulary and Block Design), from strategy B. All three short-forms showed a strong and significant correlation with the FSIQ and were considered psychometrically acceptable. Arguments in favor of Proposal B1 are discussed. Assessing FSIQ with these short-forms will be useful for avoiding long assessment procedures in a population characterized by high fatigability.

Unravelling the impact of frontal lobe impairment for social dysfunction in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is an autosomal dominant multisystemic disorder affecting muscular and extra muscular systems, including the central nervous system. Cerebral involvement in myotonic dystrophy type 1 is associated with subtle cognitive and behavioural disorders, of major impact on socio-professional adaptation. The social dysfunction and its potential relation to frontal lobe neuropsychology remain under-evaluated in this pathology. The neuroanatomical network underpinning that disorder is yet to disentangle. Twenty-eight myotonic dystrophy type 1 adult patients (mean age: 46 years old) and 18 age and sex-matched healthy controls were included in the study. All patients performed an exhaustive neuropsychological assessment with a specific focus on frontal lobe neuropsychology (motivation, social cognition and executive functions). Among them, 18 myotonic dystrophy type 1 patients and 18 healthy controls had a brain MRI with T1 and T2 Flair sequences. Grey matter segmentation, Voxel-based morphometry and cortical thickness estimation were performed with Statistical Parametric Mapping Software SPM12 and Freesurfer software. Furthermore, T2 white matter lesions and subcortical structures were segmented with Automated Volumetry Software. Most patients showed significant impairment in executive frontal functions (auditory working memory, inhibition, contextualization and mental flexibility). Patients showed only minor difficulties in social cognition tests mostly in cognitive Theory of Mind, but with relative sparing of affective Theory of Mind and emotion recognition. Neuroimaging analysis revealed atrophy mostly in the parahippocampal and hippocampal regions and to a lesser extent in basal ganglia, regions involved in social navigation and mental flexibility, respectively. Social cognition scores were correlated with right parahippocampal gyrus atrophy. Social dysfunction in myotonic dystrophy type 1 might be a consequence of cognitive impairment regarding mental flexibility and social contextualization rather than a specific social cognition deficit such as emotion recognition. We suggest that both white matter lesions and grey matter disease could account for this social dysfunction, involving, in particular, the frontal-subcortical network and the hippocampal/arahippocampal regions, brain regions known, respectively, to integrate contextualization and social navigation.

Analysis of Dp71 contribution in the severity of mental retardation through comparison of Duchenne and Becker patients differing by mutation consequences on Dp71 expression.

The presence of variable degrees of cognitive impairment, extending from severe mental retardation to specific deficits, in patients with dystrophinopathies is a well-recognized problem. However, molecular basis underlying mental retardation and its severity remain poorly understood and still a matter of debate. Here, we report one of the largest study based on the comparison of clinical, cognitive, molecular and expression data in a large cohort of 81 patients affected with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) bearing mutations predicted to affect either all dystrophin products, including Dp71 or all dystrophin products, except Dp71. In addition to the consistent data defining molecular basis underlying mental retardation in DMD, we show that BMD patients with MR have mutations that significantly affect Dp71 expression or with mutations located in exons 75 and 76. We also show that mutations upstream to exon 62, with DMD phenotype, predicted to lead to a loss-of-function of all dystrophin products, except Dp71 isoform, are associated, predominantly, with normal or borderline cognitive performances. Altogether, these reliable phenotype-genotype correlations in combination with Dp71 mRNA and protein expression studies, strongly indicate that loss-of-function of all dystrophin products is systematically associated with severe form of MR, and Dp71 deficit is a factor that contributes in the severity of MR and may account for a shift of 2 SD downward of the intelligence quotient.

Executive function and theory of mind in school-aged children after neonatal corrective cardiac surgery for transposition of the great arteries.

AIM: cardiac malformations resulting in cyanosis, such as transposition of the great arteries (TGA), have been associated with neurodevelopmental dysfunction. The purpose of this study was to assess, for the first time, theory of mind (ToM), which is a key component of social cognition and executive functions in school-aged children with TGA. METHOD: twenty-one children (14 males, seven females; mean age 7y 4mo; SD 3mo) who underwent neonatal open-heart surgery for TGA using full-flow cardiopulmonary bypass were compared with 21 typically developing age-matched children (12 males, nine females; mean age 7y 6mo; SD 3.8mo) using different neuropsychological measures specifically designed to assess executive function (cognitive and response inhibition, verbal and spatial working memory, and planning). They were also given two ToM tasks (first- and second-order false belief understanding). RESULTS: general IQ was within the normal range in both the TGA group and the comparison group (mean IQ 113 [SD 9.3] and 118 [SD 10.1] respectively), but performance on all executive functions and on ToM (first and second level) was significantly lower in the TGA group (p values of 0.02, 0.01, and 0.004 respectively). A discriminant multivariate analysis provided evidence for cognitive and behavioural inhibition as well as performance on false belief tasks as being the most important contributors to the differentiation between the groups (p=0.03). INTERPRETATION: children with TGA demonstrate great difficulties in exerting cognitive and behavioural inhibition. They also present specific deficits in false belief understanding, which were related to immature executive abilities.

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission.

Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1.

PURPOSE OF REVIEW: Myotonic dystrophy type 1 is a multisystemic disorder caused by a noncoding triplet repeat. The age of onset is variable across the lifespan, but in its most severe form, the symptoms appear at birth (congenital myotonic dystrophy) or in the pediatric age range (childhood-onset myotonic dystrophy). These children have a range of disabilities that reduce the lifespan and cause significant morbidity. Currently, there are no agreed upon recommendations for caring for these children. RECENT FINDINGS: The Myotonic Dystrophy Foundation recruited 11 international clinicians who are experienced with congenital and childhood-onset myotonic dystrophy to create consensus-based care recommendations. The experts used a 2-step methodology using elements of the single text procedure and nominal group technique. Completion of this process has led to the development of clinical care recommendations for this population. SUMMARY: Children with myotonic dystrophy often require monitoring and interventions to improve the lifespan and quality of life. The resulting recommendations are intended to standardize and improve the care of children with myotonic dystrophy.

Consensus-based care recommendations for adults with myotonic dystrophy type 1.

PURPOSE OF REVIEW: Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. RECENT FINDINGS: The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. SUMMARY: The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.

Cognitive profile in childhood myotonic dystrophy type 1: is there a global impairment?

The objective of this study was to assess the cognitive profile in the childhood-onset form of myotonic dystrophy (DM1). We carried out a general cognitive abilities study on 36 patients (6-18 years). Results of Full Scale IQ , VIQ (Verbal IQ) and PIQ (Performance IQ) measures are discussed in terms of global cognitive impairment depending on the (CTG)n repeat size and the transmitting parent's sex. The results highlighted a negative correlation between the CTG repeat size and cognitive function: (1) 55% of the subjects (20/34) presented large CTG expansion (mean=761) correlated with significant extensive cognitive deficits (mean Full Scale IQ=56) in both intelligence scales (verbal and non-verbal); most of them exhibited DM1 maternal transmission. (2) In the case of smaller expansion (mean=527), 38% of the subjects exhibited a subnormal intelligence (mean Full Scale IQ=86) but performed poorly on subtests evaluating attention/memory function and presented a severe deficit in visuospatial and/or visuo-constructive skills. Most of these children had paternal transmission but a few had an affected mother.

Executive functions development in 5- to 7-year-old children with transposition of the great arteries: a longitudinal study.

This longitudinal study investigates executive functions (EF) in children with transposition of the great arteries (TGA) compared to typically developing children at a key age period between 5 and 7 years. We explored the presence and evolution of specific impairments on three core EF components (inhibition, working memory, and cognitive flexibility). Ninety children were evaluated for three consecutive years. Results demonstrated significant delays in inhibition and cognitive flexibility despite normal working memory. Impairments did not systematically worsen with age. EF impairments after TGA are dynamic and may affect selective components. Cyanotic congenital heart disease is associated with altered EF development.

A new window on neurocognitive dysfunction in the childhood form of myotonic dystrophy type 1 (DM1).

Not much is known about the neurocognitive deficits in the childhood phenotypic expression of DM1. Twenty-four children and adolescents with no mental retardation were administered an extensive neuropsychological battery to investigate cognition in terms of memory, executive functions and visuo-spatial abilities. The results showed discrepancies between Wechsler's indexes with higher scores in Verbal Comprehension than Perceptive Organization and Speed of Processing. Memory assessment using Signoret's Memory Battery revealed a clear difference between verbal and visuospatial memory but no impairment between short and long-term memory. Concerning executive abilities, DM1 subjects showed greater deficits in processing speed than in mental flexibility, inhibition or working memory. This pattern of deficits could implicate a frontoparietal circuit in accordance with the neural networks involved in the adult form of DM1 and reopens the question of a continuum between childhood and adulthood neurocognitive impairments.