Absence Of Intellectual Disability Research Articles

Analysis of factors influencing the efficacy of vagus nerve stimulation for the treatment of drug-resistant epilepsy in children and prediction model for efficacy evaluation.

Vagus nerve stimulation (VNS) has been widely used in the treatment of drug-resistant epilepsy (DRE) in children. We aimed to explore the efficacy and safety of VNS, focusing on factors that can influence the efficacy of VNS, and construct a prediction model for the efficacy of VNS in the treatment of DRE children. Retrospectively analyzed 45 DRE children who underwent VNS at Qilu Hospital of Shandong University from June 2016 to November 2022. A ≥50% reduction in seizure frequency was defined as responder, logistic regression analyses were performed to analyze factors affecting the efficacy of VNS, and a predictive model was constructed. The predictive model was evaluated by receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA). A total of 45 DRE children were included in this study, and the frequency of seizures was significantly reduced after VNS treatment, with 25 responders (55.6%), of whom 6 (13.3%) achieved seizure freedom. There was a significant improvement in the Quality of Life in Childhood Epilepsy Questionnaire (15.5%) and Seizure Severity Score (46.2%). 16 potential factors affecting the efficacy of VNS were included, and three statistically significant positive predictors were ultimately screened: shorter seizure duration, focal seizure, and absence of intellectual disability. We developed a nomogram for predicting the efficacy of VNS in the treatment of DRE children. The ROC curve confirmed that the predictive model has good diagnostic performance (AUC = 0.864, P < 0.05), and the nomogram can be further validated by bootstrapping for 1,000 repetitions, with a C-index of 0.837. Besides, this model showed good fitting and calibration and positive net benefits in decision curve analysis. VNS is a safe and effective treatment for DRE children. We developed a predictive nomogram for the efficacy of VNS, which provides a basis for more accurate selection of VNS patients.

Long-term prognosis of low language proficiency in children

Objectives This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: Primary objectives Population Children between four and eight years of age, diagnosed with a language disorder, or determined to have low language proficiency before age eight. Intervention Not applicable, this is a review of observational studies and will not include active interventions. Comparator The comparison group will be peers or siblings with typically developing language skills, that is, no identified language disorder or low language proficiency. Outcome We will include the following outcomes if measured when participants are at least 12 years old (adolescents and adults): Proximal outcomes in language and literacy (outcomes within the same domain as the original assessments: omnibus tests of expressive, receptive (including listening comprehension), total language, vocabulary, grammar, narrative or expository discourse, clinical markers, such as nonsense word repetition, sentence repetition, or both) World Health Organization quality of life outcomes across five domains: physical (including general health, sleep and energy, sexual health); psychological (including mental health, self‐esteem, memory, learning, and concentration); independence (including activities of daily living, occupational outcomes, dependence on medicinal and non‐medicinal drugs and supports, independent living); social relationships (including friendships, romantic relationships, parenthood, peer problems, and anti‐social behaviour); environment (including academic outcomes, work satisfaction, financial resources, societal participation in leisure/community activities, safety). Timing Studies must have traced the individuals into adolescence, or transition to adulthood or adulthood, or both, thus, when participants are 12 years and older. Setting Identification, or assessment and diagnosis using standard diagnostic algorithms. Precise measures and cutoffs on standardised tests will vary from study to study. For instance, Tomblin 1997 used the diagnostic algorithm of < ‐1.25 standard deviations on two or more language composite scores; and in Norbury 2016, language disorder was defined as scores of −1.5 standard deviations or below on two of five language composites in the absence of intellectual disability, existing medical diagnosis, or both. Identification by speech‐language pathologists, educational psychology services, or in the context of research (population studies). Identification includes measures of language, such as vocabulary, grammar, morphosyntax, narrative. It can be expressive measure(s), receptive measure(s), or both. We will exclude identification made on the basis of tests of phonology/speech production, pragmatics, reading, or working memory only. We will include large‐scale population studies in which low language proficiency may be determined by a cut‐off of at least ‐1 standard deviation on at least one standard test of language to assess longitudinal relationships between single measures and quality of life outcomes in large community samples (Beitchman 2014; Caspi 2016; Thornton 2021). The main objective of this review is to assess the long‐term prognosis of an early language disorder or low language proficiency (LLP) for children aged four to eight years at baseline, and from age 12 years and up at follow‐up, in areas of language and literacy, and broad quality of life outcomes in physical, psychological, independence, social relationships, and environment outcomes. This will include measures of mental and physical health, academic outcome, employment status, financial resources, and societal participation. We will ask the following research questions: 1) To what extent do children with LLP age four to eight years show higher risk for persistent difficulties with language and literacy into adolescence and adulthood? 2) To what extent do children age four to eight years, with LLP, experience higher risk for poor quality of life across five domains of physical, psychological, independence, social relationships, and environment well‐being in adolescence, and adulthood (WHO 2012)? Secondary objectives Secondary objectives are: 1) to understand how severity of early language problems affects long‐term prognosis and quality of life, and 2) to identify gaps in the extant research. For instance, while the indicative sample of papers consistently report academic and employment outcomes, there is little evidence regarding physical or medical health outcomes. Investigation of sources of heterogeneity between studies We expect that there will be substantial heterogeneity between the included studies on the following variables: Diagnostic criteria Severity of language impairment Method of ascertainment (population study versus recruitment from special schools or clinics) Year of publication Age of outcome measurement Inclusiveness of non‐verbal IQ (Specific Language Impairment versus Developmental Language Disorder) Stability of schooling (e.g. special school consistently versus changing between special school and mainstream classrooms) Literacy skills

Epidemiological aspects in phenylketonuria patients from a region in northwestern Romania

Introduction. Phenylketonuria (PKU), a genetic disease with autosomal dominant transmission, is the most frequent inborn error in aminoacidic metabolism. The variations in phenylalanine-hydroxylase (PAH) gene lead to a lowered enzymatic activity causing hyperphenylalaninemia. PKU has a mean European prevalence of 1:10,000 newborns, with a large variation in different ethnicities and geographic regions. The large genetic variability (over 1200 genetic variants known) as well as other factors determines a wide spectrum of metabolic phenotypes. Untreated, PKU leads to irreversible intellectual disability, low stature, hypopigmentation, motor deficits, seizures, but the early diagnosis and treatment enables almost normal somatic and mental development. Aim. The aim of this study is the determination of the impact of non-genetic factors over the clinical phenotype of PKU patients in a region of north-west Romania. Material and method. The study group is formed from 44 patients diagnosed with phenylketonuria in the 1981 – 2021 period, found in the database of Bihor Regional Center for Medical Genetics, Emergency Clinical County Hospital, Oradea, Romania. The collected data was referring to the age, sex and domicile of the patients, the age of the diagnosis and the beginning of the treatment, also the metabolic control over the years, the metabolic phenotype of the patients and its impact on the clinical phenotype (IQ, the presence or absence of intellectual disability or the existence of a specific clinical phenotype). Results. The majority of patients (66%) were diagnosticated with phenylketonuria in the first 4 months of life, although there were cases with a late diagnosis, 20.5% of the patients were diagnosticated after the age of 1 year. Based on the pre-treatment plasmatic levels of phenylalanine, the majority of cases (72.7%) had a severe metabolic phenotype (classic PKU - cPKU), 20.5% of cases had a milder form of PKU (mPKU) and 6.8% of patients were found with a mild hyperphenylalaninemia (HPA). In the case of 23 patients, an optimal metabolic control was not obtained. The specific phenotype (blonde hair, light skin, blue eyes) was found in 22.7% of cases, 77.3% not having these features. At 68.2% of cases intellectual disability was found, with different levels of severity: 5 patients (11.5%) had liminal intellect, 9 patients (20.5%) had mild mental retardation, 6 patients (13.6%) had moderate mental retardation, 9 cases (20.5%) were with severe mental retardation and 1 patient (2.3%) had profound mental retardation; 31.8% of cases had normal intellect. The prevalence in Bihor county is 1:7,843 newborns. Discussions. A partial or, in rare cases, total lack of dietetic treatment was observed in all patients over 20 years old (current age). The delay in treatment initiation or an insufficient treatment, with a suboptimal metabolic control, will affect patient’s intellect, regardless of metabolic phenotype. If in 20 years old patients, or older, the main reason for mental retardation is the lack of dietetic treatment availability in the first years of life, for the younger patients the reason for mental retardation is usually a lack of compliance with the treatment. The majority of metabolic phenotypes is cPKU, in concordance with the literature data; the mild phenotype (HPA) was observed in a small percentage of patients, smaller than the data reported in the literature. In the first two studied decades the mild phenotypes were seldom observed. In the absence of screening tests or suggestive clinical manifestation it can be assumed that HPA patients remained undiagnosed, which would explain the small HPA percentage in the study group. A significant improvement in metabolic control in younger patients compared with older ones was observed, which denotes a better access to specific alimentation on one side, and o the other side, a better understanding of the disease from the patients and their families. Also, this study confirms a known fact that the diet in PKU is of great importance in the disease evolution. In this study there were included patients with severe metabolic phenotype with good metabolic control which reached adulthood without intellectual deficits, with higher education, social integrated and also patients with mild metabolic phenotype but with a poor metabolic control which developed intellectual deficiency. Conclusions. The PKU prevalence in Bihor county is higher than the estimated national value. The late diagnosis and treatment or the poor metabolic control led to intellectual disability, regardless of the metabolic phenotype. PKU screening and the better access to treatment allows younger generations of patients to enjoy a superior quality of life than the patients from the first two studied decades.

Relationship between cognitive ability and predictors for age at the time of autism spectrum disorder diagnosis

The rising prevalence of autism spectrum disorder (ASD) has increased awareness of the need for early diagnosis and intervention; however, not all children are diagnosed at preschool age. In the literature, findings regarding factors that may play a role in later diagnosis are inconsistent. Presence or absence of intellectual disability is a possible factor. This study aimed to identify factors associated with later diagnosis of ASD among children grouped according to low and high cognitive levels. Data of children who were previously diagnosed with ASD between 2002 and 2016 at a national autism center were analyzed. Better cognitive ability, having more siblings, and previous diagnosis of attention-deficit/hyperactivity disorder were predictors of later diagnosis among the entire cohort. Children exhibiting lower cognitive levels (LC-ASD; DQ/IQ < 70; n = 209) were diagnosed much earlier. Among this group, later ASD diagnosis was predicted by poorer adaptive behavior, more severe restricted and repetitive behaviors, and previous diagnosis of epilepsy. In the higher cognitive level group (HC-ASD; DQ/IQ ≥ 70; n = 321), familial variables and more severe social impairments were predictors of later ASD diagnosis. Clinicians should be aware of variables that may affect ASD diagnostic age among children with varying cognitive abilities.

EVALUATING THE PREVALENCE AND FACTORS ASSOCIATED WITH AN OPTIMAL NEURODEVELOPMENTAL OUTCOME IN CHILDREN WITH FONTAN CIRCULATION

<h3>BACKGROUND</h3> While youth with Fontan circulation are at increased risk for adverse neurodevelopmental outcomes, not all children encounter these limitations. We sought to evaluate the prevalence and factors associated with "optimal" neurodevelopmental outcomes in 4-6 year old children with Fontan circulation. <h3>METHODS AND RESULTS</h3> Patients who underwent the Fontan procedure born between September 1996 and December 31, 2015 and followed through the Western Canadian Complex Pediatric Therapies Follow-up Program (CPTFP) were included. All patients underwent a comprehensive neurocognitive assessment between 48-72 months of age. A composite outcome termed optimal neurodevelopmental outcome was defined as the absence of intellectual disability (full-scale intellectual quotient (FSIQ) < 80, visual motor index < 80, adaptive behavior assessment system, general adaptive composite < 80), chronic motor disability, permanent hearing loss, visual impairment, seizure disorder, or autism spectrum disorder. Multivariable regression models and decision algorithms (utilizing variables from the multivariable regression analysis, with cut-points determined to optimize a global accuracy index) were generated to evaluate demographic and clinical factors associated with optimal neurodevelopmental outcome. The Fontan procedure was completed on 225 children in the study period, with neurodevelopmental outcome data available for 205 (age at Fontan 3.4 +/- 0.9 years, age at assessment 4.6 +/- 0.5 years, 37% female). Optimal neurodevelopmental outcome was identified in 55% (112/205). In the multivariable regression analysis, factors independently associated with an increased odds ratio of optimal neurodevelopmental outcome were female sex [2.1 (95% confidence interval (CI) 1.1-4.1)], years of maternal schooling [1.2 (1.1-1.5)], age at Fontan (years) [0.97 (0.9-1.0)], need for concomitant atrioventricular valve (AVV) intervention [0.4 (0.2-1.0)], and time (hours) for lactate to be < 2mmol/L [0.9 (0.8-1.0)]. There was a wide range in the prevalence of optimal neurodevelopmental outcomes according to the presence or absence of clinical and demographic variables (Table). For example, if a patient was < 3.25 years at Fontan, did not have a concomitant AVV intervention, and the lactate was < 2mmol/L within eight hours post-operatively, 87% (27/31) had an optimal neurodevelopmental outcome. Conversely, the absence of each of these variables (>/=3.25 years, need for AVV intervention, and >/=8 hours to clear lactate) was associated with 7% (1/14) having optimal neurodevelopmental outcomes. <h3>CONCLUSION</h3> Optimal neurodevelopmental outcome was present in over half of 4-6 year old children with Fontan circulation in this single-center study, with important associated factors identified, including potentially modifiable factors such as younger age at Fontan and lack of concomitant AVV intervention. Multi-center evaluations are needed to further evaluate this previously undefined composite outcome.

Risk-benefit assessment of treatment of epileptic women of childbearing age with valproic acid

AimValproic acid (VPA) is a widely used anti-epileptic drug (AED) of demonstrated efficacy. However, its teratogenic effects have resulted in many regulatory agencies recommending that it should not be administered to women of childbearing age unless they are taking contraceptives. The aim of this study was to determine the willingness of candidate patients to change their treatment and to monitor the evolution of their attitude. MethodsWe identified patients aged between 15 and 45 years old who had been diagnosed with epilepsy and were being treated with VPA. A shared decision-making visit was arranged, during which variables related to their epilepsy were recorded. The patients were informed about the teratogenic effects of VPA and the risks/benefits of a change in treatment. The patient, or legal guardian, then freely chose the course of treatment that they wished to follow. On a follow-up visit, six months later, seizure control and tolerance to the chosen treatment were recorded. The variables related to each patient’s willingness to their change treatment were analysed. ResultsA total of 60 patients, with a median age of 32.7 years, were included in the study. Of these, 25 (41.7%) suffered some form of intellectual disability. Only one (1.7%) had poor seizure control. After the initial visit, 41 patients (68%) opted to continue with the VPA treatment, six opted to stop receiving VPA, and 13 decided to switch to another AED. The median age of the patients who opted to change treatment was significantly lower than that of those who opted to continue with the VPA treatment (29.1 vs. 34.4, p = 0.024). The absence of intellectual disability (p = 0.047) and a length of treatment of less than five years (0.016) were both significantly associated with the decision to change treatment. Of the 19 patients who changed treatment, nine (47%) returned to the initial treatment with VPA. ConclusionsDespite being informed of the teratogenic risk associated with VPA, a significant number of patients and legal guardians opted to continue with this treatment; the reasons given for this were the low possibility of pregnancy and the risk of breakthrough seizures. In almost half the cases studied, the pharmacological alternatives to VPA were poorly tolerated and did not provide a good level of seizure control.

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study.

Background and PurposeThe US Food and Drug Administration approval for perampanel has only recently been expanded to patients as young as 4 years, and so there have been few real-life studies of the effects of perampanel in pediatric patients. The aim of this study was to determine the long-term efficacy, factors affecting treatment response, and tolerability of perampanel as an add-on therapy in pediatric patients aged 4 years or older with epilepsy.MethodsThis multicenter retrospective observational study collected data from pediatric epilepsy centers of four Korean national universities. Changes in the seizure frequency from baseline, adverse events, and retention rates were obtained at 3, 6, and 12 months. Adverse events and discontinuation profiles were obtained to assess tolerability.ResultsThis study included 220 children and adolescents (117 males and 103 females) aged 4 to 20 years. The overall response rate was 43.6%, and the seizure-freedom rate was 17.7%. Factors affecting a good treatment response were the absence of intellectual disability, small number of concomitant antiepileptic drugs, and low baseline seizure frequency. Eighty-eight patients (40%) experienced adverse events, but they mostly were of mild severity and resolved after the dose reduction or discontinuation of perampanel. The retention rates at 3, 6, and 12 months were 85.0%, 71.8%, and 50.5%, respectively.ConclusionsAdjunctive treatment with perampanel was efficacious and tolerated in pediatric patients aged 4 years or older with epilepsy. Early perampanel treatment may help to reduce the burden of their seizures and improve their quality of life.

15.2 UTILIZING AN EVENT-RELATED POTENTIAL BIOMARKER TO MEASURE THE EFFECTS OF BRIEF, TARGETED EXECUTIVE FUNCTION TRAINING FOR CHILDREN WITH ASD

ASD is associated with lifelong impairments in executive function (EF), even in the absence of intellectual disability. An emerging literature describes approaches to training EF skills among typically developing children. In these training studies, electrophysiology provides a tool for probing aspects of EF not captured by overt behavioral responses, such as response preparation, monitoring, and inhibition. The N2 ERP component is linked to conflict monitoring, distinguishes children with ASD from control subjects, and relates to behavioral inhibition and interference suppression among children with ASD.

Autosomal-dominant early-onset spastic paraparesis with brain calcification due to IFIH1 gain-of-function.

We describe progressive spastic paraparesis in two male siblings and the daughter of one of these individuals. Onset of disease occurred within the first decade, with stiffness and gait difficulties. Brisk deep tendon reflexes and extensor plantar responses were present, in the absence of intellectual disability or dermatological manifestations. Cerebral imaging identified intracranial calcification in all symptomatic family members. A marked upregulation of interferon-stimulated gene transcripts was recorded in all three affected individuals and in two clinically unaffected relatives. A heterozygous IFIH1 c.2544T>G missense variant (p.Asp848Glu) segregated with interferon status. Although not highly conserved (CADD score 10.08 vs. MSC-CADD score of 19.33) and predicted as benign by in silico algorithms, this variant is not present on publically available databases of control alleles, and expression of the D848E construct in HEK293T cells indicated that it confers a gain-of-function. This report illustrates, for the first time, the occurrence of autosomal-dominant spastic paraplegia with intracranial calcifications due to an IFIH1-related type 1 interferonopathy.

Neurocognitive Correlates of Attention-Deficit Hyperactivity Disorder Symptoms in Children Born at Extremely Low Gestational Age.

Compared with children born near term, those born extremely preterm (EP) are at much higher risk for attention-deficit hyperactivity disorder (ADHD). Little information is available about differences in neuropsychological outcomes among EP children with and without ADHD. Our analyses aimed to evaluate the neuropsychological correlates of ADHD symptoms in extremely low gestational age newborns (ELGANs). We obtained Child Symptom Inventory-4 reports from parents (n = 871) and teachers (n = 634) of 10-year-old children born before the 28th week of gestation. Participants completed standardized assessments of neurocognitive and academic functioning. In the total sample, children who screened positive for ADHD symptoms were at increased risk for neurocognitive limitations. These associations were weaker when the sample was limited to those with intelligence quotient (IQ) ≥70 or ≥85. Even those with IQ ≥85 who screened positive for ADHD symptoms were more likely than their peers to have deficits on the DAS-II Working Memory Cluster and the NEPSY-II Auditory Response subtest. The risks for impaired academic performance (Z ≤ -1) on components of the WIAT-III were 2-to-3 times higher in this group than among ELGANs not classified as having ADHD symptoms. Among children born EP, those with ADHD symptoms are more likely to have global neurocognitive impairment. When IQ is within normal limits, ADHD symptoms are associated with deficits in executive functioning skills. These findings highlight a group at risk for executive functioning deficits and related academic difficulties, even in the absence of intellectual disability.

Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder.

Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social-communicative functioning and repetitive behaviors in a stratified cross-sectional sample of 324 youth with ASD in the absence of intellectual disability, and 438 TD youth (aged 4-29years). An age-by-group interaction emerged indicating that TD youth exhibited age-related improvements in social-communication scores while the ASD group demonstrated age-related declines in these scores. This suggests that adolescents/adults with ASD may fall increasingly behind their same-age peers in social-communicative skills.

Neuropsychological assessment of children with epilepsy and average intelligence using NEPSY II

Introduction: Many studies have shown altered neuropsychological functioning of children with epilepsy even in the absence of intellectual disability, with notable concerns for both patients and their families. Although studies have described the cognitive profiles associated with specific epilepsy syndromes, there is incomplete agreement on the relation between spared and impaired abilities in different cognitive domains and on how deficits in one neuropsychological ability can secondarily affect performance in other cognitive domains. The aim of this study was to investigate the neuropsychological profile and vulnerabilities of children with epilepsy without intellectual disability or borderline intellectual functioning. Method: 23 children aged 7–15 years, with a diagnosis of epilepsy of genetic or unknown cause and average intellectual functioning (IQ >85), were administered all age-appropriate tests of the Italian-language version (Urgesi, Campanella, & Fabbro, 2011) of a comprehensive neuropsychological battery (NEPSY–II: A Developmental Neuropsychological Assessment, Second Edition; Korkman, Kirk, & Kemp, 2007). Their performance was compared with that of a control group matched for gender, age, handedness and education. Results: Children with epilepsy showed significant impairments as compared to the control group in tests of attention and executive functions and sensorimotor skills. Notably, particular difficulties were observed also in social perception tasks that require affect recognition, an ability that has been so far poorly considered in children with epilepsy. Conclusions: The results highlight the importance of performing extensive evaluation of cognitive functions, including social cognition processes, in children with epilepsy with average intelligence in order to design appropriate interventions aimed at minimizing long-term consequences on educational and behavioral outcome.

Copy Number Variation Screen Identifies a Rare De Novo Deletion at Chromosome 15q13.1-13.3 in a Child with Language Impairment.

A significant proportion of children (up to 7% in the UK) present with pronounced language difficulties that cannot be explained by obvious causes like other neurological and medical conditions. A substantial genetic component is predicted to underlie such language problems. Copy number variants (CNVs) have been implicated in neurodevelopmental and psychiatric conditions, such as autism and schizophrenia, but it is not fully established to what extent they might contribute to language disorders. We conducted a CNV screen in a longitudinal cohort of young children with language-related difficulties (n = 85), focusing on single events at candidate loci. We detected a de novo deletion on chromosome 15q13.1–13.3. The adjacent 15q11-13.1 locus is disrupted in Prader-Willi and Angelman syndromes, while disruptions across the breakpoints (BP1-BP6) have previously been implicated in different neurodevelopmental phenotypes including autism, intellectual disability (ID), seizures and developmental delay (DD). This is the first report of a deletion at BP3-BP5 being linked to a deficit confined to language impairment, in the absence of ID, expanding the range of phenotypes that implicate the chromosome 15q13 locus.

Concordance between a head circumference growth function and intellectual disability in relation with the cause of microcephaly

Abstract Introduction Our aim was to investigate the correlations between patterns of head growth and intellectual disability among distinct aetiological presentations of microcephaly. Patients and methods 3269 head circumference (HC) charts of patients from a tertiary neuropaediatric unit were reviewed and 136 microcephalic participants selected. Using the Z -scores of registered HC measurements we defined the variables: HC Minimum, HC Drop and HC Catch-up. We classified patients according to the presence or absence of intellectual disability (IQ below 71) and according to the cause of microcephaly (idiopathic, familial, syndromic, symptomatic and mixed). Results Using discriminant analysis a C -function was defined as C = HC Minimum + HC Drop with a cut-off level of C = −4.32 Z -score. In our sample 95% of patients scoring below this level, severe microcephaly, were classified in the disabled group while the overall concordance was 66%. In the symptomatic-mixed group the concordance between HC function and outcome reached 82% in contrast to only 54% in the idiopathic-syndromic group ( P -value = 0.0002). Conclusions We defined a HC growth function which discriminates intellectual disability of microcephalic patients better than isolated HC measurements, especially for those with secondary and mixed aetiologies.

Concordancia entre una función de crecimiento del perímetro cefálico y la discapacidad intelectual en relación con la etiología de la microcefalia

IntroductionOur aim was to investigate the correlations between patterns of head growth and intellectual disability among distinct ætiological presentations of microcephaly. Patients and methods3,269 head circumference (HC) charts of patients from a tertiary neuropædiatric unit were reviewed and 136 microcephalic participants selected. Using the Z-scores of registered HC measurements we defined the variables: HC Minimum, HC Drop and HC Catch-up. We classified patients according to the presence or absence of intellectual disability (IQ below 71) and according to the cause of microcephaly (idiopathic, familial, syndromic, symptomatic and mixed). ResultsUsing Discriminant Analysis a C-function was defined as C=HC Minimum + HC Drop with a cut-off level of C=-4.32 Z-score. In our sample 95% of patients scoring below this level, severe microcephaly, were classified in the disabled group while the overall concordance was 66%. In the symptomatic-mixed group the concordance between HC function and outcome reached 82% in contrast to only 54% in the idiopathic-syndromic group (P-value=0.0002). ConclusionsWe defined a HC growth function which discriminates intellecutal disability of microcephalic patients better than isolated HC measurements, especially for those with secondary and mixed ætiologies.

The association between congenital anomalies and autism spectrum disorders in a Finnish national birth cohort.

The first aim of this study was to evaluate the association between different subgroups of autism spectrum disorders (ASDs) (childhood autism, Asperger syndrome, and pervasive developmental disorder/pervasive developmental disorder - not otherwise specified [PDD/PDD-NOS]) and congenital anomalies. Second, we assessed the association among intellectually disabled children with ASDs in the subgroups of childhood autism and PDD/PDD-NOS. Nationwide population-based register data for children with a diagnosis of ASD (n=4449; 3548 males, 901 females) were collected during years 1987-2000 from the Finnish Hospital Discharge Register. Data on congenital anomalies were derived from the National Register of Congenital Malformations. Conditional logistic regression models were used as a statistical method. The association between ASD subgroups and congenital anomalies was stratified by the presence or absence of intellectual disability. Congenital anomalies occurred more frequently in all subgroups of ASD than in comparison participants (adjusted odds ratio [OR] for major congenital anomalies 1.8, 95% confidence interval [CI] 1.5-2.2, p<0.001). The association between congenital anomalies and childhood autism (OR 2.4, 95% CI 1.6-3.6, p<0.001) and between congenital anomalies and PDD/PDD-NOS (OR 3.7, 95% CI 2.4-5.7, p<0.001) among children with an intellectual disability was strong but remained significant also without intellectual disability (childhood autism: OR 1.7, 95% CI 1.3-2.3, p<0.001; PDD/PDD-NOS: OR 2.3, 95% CI 1.9-2.8, p<0.001). The results suggest a significant association between ASDs and congenital anomalies regardless of the ASD subgroup. The association between childhood autism and PDD/PDD-NOS and congenital anomalies is stronger among children with intellectual disability is stronger than among those without intellectual disability. These results may have relevance in examining early risk factors in autism during fetal neurodevelopment.

Most adults with childhood-onset epilepsy and their parents have incorrect knowledge of the cause 20–30 years later: A population-based study

RationaleUnderstanding the cause of childhood-onset epilepsy should be important for families and the patient as he/she becomes an adult. We studied the accuracy of information about the cause that adults with childhood-onset epilepsy and their parents reported many years after the initial diagnosis. MethodsPatients and parents in the Nova Scotia childhood-onset epilepsy population-based study were contacted. All patients developed epilepsy between 1977 and 1985 with follow-up 20–30years later with a semistructured telephone interview. Of 600 eligible patients, 373 (62%) answered a question about what they thought had caused the epilepsy. ResultsWe identified a cause in 210 of 373 (56%) patients, and no cause was found in 44%. Surprisingly, only 38% of families knew the correct cause. Nearly all had been followed during childhood by a child neurologist, and all adults had a family physician. Responses were concordant in 40% with our causal diagnoses and not concordant in 60%. Responses were divided into 5 categories: (1) In 26%, the family was sure of the cause when no cause had been identified; (2) In 16%, there was a definite known cause, but families did not recall any cause at all; (3) In 18%, we did not identify a cause and neither did the family; (4) In 20%, we identified a definite cause as did the family, but the causes were completely different; and (5) In 20%, we identified a cause, the same one as the family. Correct information did not vary with broad epilepsy syndrome groupings, the presence or absence of intellectual disability, epilepsy remission, parental education, or family income. Those with intractable epilepsy were more likely to be concordant (p=0.002). None of those with Rolandic epilepsy were correct (n=41). ConclusionsMost adults with childhood-onset epilepsy and their parents have a strikingly poor recall of the cause. We suggest that families receive this information in a written document that is periodically updated, can be preserved, and can be referred to over time.

Comorbid epilepsy and psychogenic non-epileptic seizures: How well do patients and caregivers distinguish between the two

PurposeTo determine whether patients with comorbid epilepsy and psychogenic nonepileptic seizure (PNES) and their caregivers can distinguish between these two events at least one year after initial diagnosis, and to investigate factors associated with correct identification. MethodsAdult patients with at least a one year diagnosis of both epilepsy and PNES, confirmed through video-electroencephalography (VEEG), were selected. Patients and a caregiver of their choice were interviewed and shown videos containing the patients’ epileptic and PNES events. Variables associated with correct identification of events by patients and their caregivers were evaluated. ResultsTwenty-four patients participated in the study. Mean time between VEEG diagnosis and enrollment in the study was 26.8 months (±12.4). Six of patients correctly distinguished between the events shown. Factors associated with correct identification were the absence of intellectual disability, unremitted PNES, and a degree of preserved awareness during the PNES event. Twelve caregivers correctly distinguished between the events shown. Factors associated with correct identification among caregivers were the presentation of only one epileptic seizure type in the patient, and the participation of the caregiver during VEEG monitoring and communication of PNES diagnosis to the patient. ConclusionA significant proportion of patients with epilepsy and PNES and their caregivers seem to be unable to discriminate between these events a year after diagnosis. These findings have implications for both clinical follow-up and research involving this population. Future research should further investigate methods that would allow patients and their caregivers to better distinguish between these two events.

Fetal and Sociocultural Environments and Autism

Fetal and Sociocultural Environments and Autism

Cryptic 7q36.2q36.3 deletion causes multiple congenital eye anomalies and craniofacial dysmorphism

A patient with a de novo cryptic 7q36.2q36.3 deletion presented with multiple congenital eye abnormalities, short stature and craniofacial dysmorphism, in the absence of intellectual disability. This report further delineates the 7q36 microdeletion syndrome.