Cerebral creatine deficiency disorders - A clinical, genetic and follow up study from India.

INTRODUCTION: Cerebral creatine deficiency syndromes (CCDS) are a group of potentially treatable neurometabolic disorders. The clinical, genetic profile and follow up outcome of Indian CCDS patients is presented. MATERIALS AND METHODS: This was a retrospective cohort of CCDS patients seen over six-years. Diagnosis was based either on low creatine peak on proton magnetic resonance spectroscopy (MRS) and/or genetic evaluation. RESULTS: Thirteen patients were eligible [8 creatine transporter deficiency (CTD), 4 guanidinoacetate methyltransferase (GAMT) deficiency and 1 could not be classified]. The mean (±SD) age at diagnosis was 7.2(±5.0) years. Clinical manifestations included intellectual disability (ID) with significant expressive speech delay in all. Most had significant behavior issues (8/13) and/or autism (8/13). All had history of convulsive seizures (11/13 had epilepsy; 2 patients only had febrile seizures) and 2/13 had movement disorder. Constipation was the commonest non-neurological manifestation (5/13 patients). Cranial MRI was normal in all CTD patients but showed globus pallidus hyperintensity in all four with GAMT deficiency. MRS performed in 11/13 patients, revealed abnormally low creatine peak. A causative genetic variant (novel mutation in nine) was identified in 12 patients. Three GAMT deficiency and one CTD patient reported neurodevelopmental improvement and good seizure control after creatine supplementation. CONCLUSION: Intellectual disability, disproportionate speech delay, autism, and epilepsy, were common in our CCDS patients. A normal structural neuroimaging with easily controlled febrile and/or afebrile seizures differentiated CTD from GAMT deficiency patients who had abnormal neuroimaging and often difficult to control epilepsy and movement disorder.

Separating the influences of late talking and dyslexia on brain structure.

Being a late talker constitutes a risk factor for later neurodevelopmental disorders; however, its neurobiological basis remains unexplored. We aimed to determine the unique and mutual correlates of late talking and developmental dyslexia on brain structure and behavioral outcomes in a large sample of 8- to 10-year-old children in a between-groups design (N = 120). Brain structure was examined using voxel-based morphometry (to measure gray matter volume) and surface-based morphometry (to measure gray matter volume, cortical thickness, surface area, and curvature of the cortex). Behaviorally, late talking and dyslexia are independently connected to language and literacy skills, and late talkers have difficulties in grammar, phonological awareness, and reading accuracy. Children with dyslexia show impairments in all of the above, as well as in vocabulary, spelling, reading speed, and rapid automatized naming. Neuroanatomically, dyslexia is related to lower total intracranial volume and total surface area. Late talking is related to reduced cortical thickness in the left posterior cingulate gyrus and the right superior temporal gyrus, which are structures belonging to the dorsal speech articulatory-phonetic perception system. Finally, a cumulative effect of late talking and dyslexia was found on the left fusiform gray matter volume. This might explain inconsistencies in previous neuroanatomical studies of dyslexia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A New Memory Perspective on the Sentence Comprehension Deficits of School-Age Children With Developmental Language Disorder: Implications for Theory, Assessment, and Intervention.

Purpose The nature of the relationship between memory and sentence comprehension in school-age children with developmental language disorder (DLD) has been unclear. We present a novel perspective that highlights the relational influences of fluid intelligence, controlled attention, working memory (WM), and long-term memory (LTM) on sentence comprehension in children with and without DLD. This perspective has new and important implications for theory, assessment, and intervention. Method We review a large-scale study of children with and without DLD that focused on the connections between cognition, memory, and sentence comprehension. We also summarize a new model of these relationships. Results Our new model suggests that WM serves as a conduit through which syntactic knowledge in LTM, controlled attention, and general pattern recognition indirectly influence sentence comprehension in both children with DLD and typically developing children. For typically developing children, language-based LTM and fluid intelligence indirectly influence sentence comprehension. However, for children with DLD, controlled attention plays a larger indirect role. Conclusions WM plays a key role in children's ability to apply their syntactic knowledge when comprehending canonical and noncanonical sentences. Our new model has important implications for the assessment of sentence comprehension and for the treatment of larger sentence comprehension deficits.

El Trastorno del desarrollo del lenguaje (TDL): Dificultades lingüísticas y no lingüísticas / Developmental Language Disorder: Language and non-language difficulties

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Morphological Errors in Spanish-Speaking Bilingual Children With and Without Developmental Language Disorders.

Purpose The purpose of this study was to find morphological markers with good diagnostic accuracy to identify developmental language disorders (DLD) in Spanish-English bilingual children. Method The participants in this study included 66 Spanish-English bilingual children between the ages of 4;0 and 6;11 (years;months) with (n = 33) and without DLD (n = 33). We employed a comprehensive production task in Spanish to elicit morphological structures that have been previously found to be problematic for Spanish-speaking children with DLD. These structures included elements of nominal morphology (articles, direct object pronouns, adjectives, and plurals) and verbal morphology (verbs and the subjunctive mood). Logistic regression was used in this study to find a set of grammatical structures that most accurately predicted group membership. Results Spanish-English bilingual children with and without DLD significantly differed from each other in their accurate production of articles, clitics, adjectives, verbs, and the subjunctive mood. Clitics, verbs, and the subjunctive mood in isolation had adequate diagnostic accuracy. A combination of verb and subjective mood accuracy best predicted group membership in this study (sensitivity of 85% and specificity of 91%). Conclusion In addition to clitics, verbs, and the subjunctive mood, both elements of verbal morphology should be considered grammatical markers of DLD in Spanish-English bilingual children. Supplemental Material https://doi.org/10.23641/asha.13641320.

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.

The Challenge of Rich Vocabulary Instruction for Children With Developmental Language Disorder.

Purpose The aims of the study were to explore responses of children with developmental language disorder (DLD) to rich vocabulary instruction and to identify potential factors that contribute to outcomes. Method Children with DLD participated in a language intervention embedded within a science camp. Using parent and clinician reports, standardized tests, probes, notes, and video, we derived descriptions of seven of the campers who received a vocabulary intervention that incorporated principles of rich instruction. We present them here as a case series. Results Five cases responded to the intervention with modest gains in Tier 2 science vocabulary and science knowledge. One case demonstrated no response, and another was unable to complete the intervention. The latter two cases presented with triple risks: DLD, executive function deficits, and stressors associated with poverty. In comparison, the best responder also lived in poverty and had DLD, but he had intact executive function, strengths in extant vocabulary, stronger knowledge of science, better engagement in the science and language intervention activities, and was older. Other factors that seemed to contribute to outcomes included the complexity of the word forms and dosage. Conclusions Translating research on rich instruction to clinical practice is challenging. This case series motivated hypotheses about the nature of the challenge and what to do about it, the primary one being that the modest success of rich vocabulary instruction for children with DLD is not a limitation of the approach itself but rather a reflection of the difficulty of delivering the intervention while tailoring the targets, approach, and dosage to the needs of individual children with DLD. Supplemental Material https://doi.org/10.23641/asha.13667699.

Infant Regulation: Associations with Child Language Development in a Longitudinal Cohort.

OBJECTIVE: To determine whether infants who have regulatory problems (eg, sleeping, crying, and feeding problems) at 1 year of age are at increased risk of experiencing language difficulties at ages 5 and 11 years, compared with settled infants. STUDY DESIGN: Parent survey and child assessment data (n = 1131) were drawn from a longitudinal community cohort study. Latent Class Analysis identified 5 profiles of infant regulation including those who were settled (37%), had tantrums (21%), had sleep problems (25%), were moderately unsettled (13%), and severely unsettled (3%) at 12 months of age. Adjusted regression analyses examined associations between infant regulatory profiles and language ability (Clinical Evaluation of Language Fundamentals-fourth edition) at ages 5 and 11 years. RESULTS: Infants who were moderately unsettled had lower language scores at age 5 (adjusted mean difference, -3.89; 95% CI, -6.92 to -0.86) and were more likely to have language difficulties (aOR, 2.71; 95% CI, 1.28-5.75), than infants who were settled. Infants who were severely unsettled at 12 months of age, had lower language scores at ages 5 (adjusted mean difference, -7.71; 95% CI, -13.07 to -2.36) and 11 (adjusted mean difference, -6.50; 95% CI, -11.60 to -1.39), than infants who were settled. Severely unsettled infants were 5 times more likely to have language difficulties at age 5 than their settled counterparts (aOR, 5.01; 95% CI, 1.72-14.63). CONCLUSIONS: Children at 1 year of age with multiple regulatory problems are at an increased risk for poorer language skills at ages 5 and 11 years.

The phenotypic spectrum of X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy.

OBJECTIVE: Asparagine-linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis. METHODS: We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants. RESULTS: The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one-half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one-third of all cases paroxysms of fast activity with electrodecrement. ALG13-related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one-third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired. SIGNIFICANCE: X-linked ALG13-related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.

The relationship between developmental language disorder and dyslexia in European Portuguese school-aged children.

Developmental Language Disorder (DLD) [Also referred to as Specific Language Impairment (SLI)] and dyslexia are neurodevelopmental disorders which show similar behavioral manifestations. In this study, between-group comparisons and frequency analysis were combined to investigate the relationship between DLD and dyslexia. European Portuguese children aged 7-10 years, with DLD (N = 7) or dyslexia (N = 11) were recruited and compared to age-matched typically developing (TD) children (N = 21) on phonological processing, language andf literacy measures. The between-group comparison revealed that for phonological processing, the clinical groups scored significantly below TD children on most tasks, yet the DLD group performed similarly to TD children for RAN speed and digit span. The clinical groups did not statistically differ in their phonological processing abilities. For language abilities, children with dyslexia did not differ from TD children, whilst children with DLD performed significantly below TD children on all measures and significantly below children with dyslexia for vocabulary. Finally, for literacy measures, there were no statistical differences between clinical groups which underperformed on all measures when compared to TD children. The frequency analysis showed that children with DLD exhibited a lower prevalence of RAN difficulties when compared to children with dyslexia, whilst children with DLD tended to show more frequent nonword repetition and phoneme deletion deficits. Additionally, whilst children with DLD consistently showed more prevalent language impairments, both clinical groups demonstrated similar prevalence rates of literacy deficits compared to TD children.These findings lend support to the additional deficit model as children with DLD show more severe and prevalent language impairments than those with dyslexia, despite similar phonological and literacy difficulties.

Neurocognitive development and capabilities in boys with 49,XXXXY syndrome.

49,XXXXY was previously associated with profound to severe intellectual deficits. However, prior research papers on the cognitive profiles of this population were confounded by small samples sizes, wide age spreads, and incomplete histories of testosterone replacement therapy. This study is the first comprehensive, international investigation of the neurocognitive aspects of 49,XXXXY, and the potential effects of biological treatment on this profile. Sixty-seven boys from infancy to 11 years of age were enrolled in this longitudinal study, with the majority of boys postnatally diagnosed though chromosomal analysis. These boys received a comprehensive neurocognitive evaluation tailored to specific language-based deficits and cognitive challenges. Results revealed higher neurocognitive capacities, both verbally and nonverbally, than previously reported in this disorder. Infant boys with 49,XXXXY who received early hormonal therapy (EHT) had significantly higher scores on the cognitive domain of the Bayley Scales of Infant Development than untreated infants (p = .013). In addition, treated school-aged participants had significantly better scaled scores than untreated boys in form completion (p = .042), a task that requires deductive reasoning, on nonverbal testing on the Leiter International Performance Scales. This study indicates greater cognitive capacities with a wide range of abilities in the child with 49,XXXXY, thus warranting further investigation to identify and understand the critical influences on the etiology and the variability of those capacities.

Speech and language development in children with 49,XXXXY syndrome.

49,XXXXY is the rarest X and Y chromosomal variation and is frequently characterized by expressive and receptive language dysfunction, low muscle tonus, and intellectual deficits. Due to the low incidence of this disorder, comprehensive studies analyzing the specific aspects of the speech and language phenotype in these boys have been uncommon. This is the first in-depth investigation of the speech and language profiles in a large cohort of boys with 49,XXXXY. Based on the clinical judgment of speech and language pathologists, there was an increased incidence (91.8%) of Childhood Apraxia of Speech (CAS), which has not been previously described in this disorder. In preschool boys, some significant differences were demonstrated between boys who received early hormonal treatment (n = 16) and untreated boys (n = 4) on the language scales (p = .047) on the Bayley Scales of Infants and Toddlers, as well as significant differences between treated (n = 13) and untreated boys (n = 8) on the Expressive One Word Picture Vocabulary Test (p = .008). No significant differences between treatment groups were found in school age children, however, treated groups demonstrated less discrepancies between expressive and receptive language. More research and larger samples are needed to determine the extent of the impact of testosterone treatment on boys with 49,XXXXY. This study identifies CAS as a potential explanation for the significant expressive language dysfunction and subsequent behavioral dysfunction. These findings may assist in facilitating more targeted treatment and improved outcomes for boys with 49,XXXXY.

49,XXXXY syndrome: A study of neurological function in this uncommon X and Y chromosomal disorder.

49,XXXXY is a rare chromosomal variation characterized by deficits in motor, language, and cognitive domains. This study reports on the neurological function and dysmorphic features in the largest cohort to date. Seventy-two boys with 49,XXXXY were evaluated on a variety of domains including a neurological examination and neuromotor assessments including the Beery Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Results supported previous literature by describing high occurrences of truncal and extremity hypotonia, which significantly impacts on motor milestones and ambulation in this population. The boys presented with dysmorphic features including epicanthal folds, frontal bossing, and synophrys. Visual perception skills were mildly impaired and cranial nerves were typically intact, however capabilities in motor coordination and fine motor precision were greatly delayed, supporting deficits in refined and controlled hand movements versus widespread visual deficits. Preschool boys treated with testosterone replacement had significantly increased scores when compared to the untreated group on the BSID-III Psychomotor Development Index, further supporting previous research indicating that testosterone replacement may have a positive impact on neurodevelopmental outcomes in males with additional X chromosomes. Boys with 49,XXXXY may benefit from hormonal treatment in conjunction with early intervention services to address their significant motor deficits.

Functional organisation for verb generation in children with developmental language disorder.

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10-15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.

An investigation into the relationship between Quality of pantomime gestures and visuospatial skills.

While children with developmental language disorder or Williams syndrome appear to use hand gestures to compensate for specific cognitive and communicative difficulties, they have different cognitive strength-weakness profiles. Their semantic and visuospatial skills potentially affect gesture quality such as iconicity. The present study focuses on untangling the unique contribution of these skills in the quality of gestures. An explicit gesture elicitation task was presented to 25 participants with developmental language disorder between 7 and 10 years of age, 25 age-matched peers with typical development, and 14 participants with Williams Syndrome (8-23 years). They gestured pictures of objects without using speech (pantomime). The iconicity, semantic richness, and representation technique of the pantomimes were coded. Participants' semantic association and visuospatial skills were formally assessed. Iconicity was slightly lower in individuals with Williams syndrome, which seems related to their visuospatial deficit. While semantic saliency was similar across participant groups, small differences in representation technique were found. Partial correlations showed that visuospatial skills and semantic skills were instrumental in producing clear pantomimes. These findings indicate that clinicians aiming to enhance individuals' natural iconic gestures should consider achieved iconicity, particularly in individuals with low visuospatial skills.

EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay.

In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. EMC10 is a bone marrow-derived angiogenic growth factor that plays an important role in infarct vascularization and promoting tissue repair. However, this gene has not been previously associated with human disease. Herein, we describe a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real-time PCR (RT-qPCR)-based expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679-1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT-qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. For the first time in the literature, the EMC10 gene variant was associated with mild ID, speech delay, and GDD. Thus, this gene plays a key role in developmental milestones, with the potential to cause neurodevelopmental disorders in humans.

Novel ALDH5A1 variants and genotype: Phenotype correlation in SSADH deficiency.

OBJECTIVE: To determine genotype-phenotype correlation in succinic semialdehyde dehydrogenase (SSADH) deficiency. METHODS: ALDH5A1 variants were studied with phenotype correlation in the SSADH natural history study. Assignment of gene variant pathogenicity was based on in silico testing and in vitro enzyme activity after site-directed mutagenesis and expression in HEK293 cells. Phenotypic scoring used a Clinical Severity Score (CSS) designed for the natural history study. RESULTS: Twenty-four patients were enrolled (10 male, 14 female, median age 8.2 years). There were 24 ALDH5A1 variants, including 7 novel pathogenic variants: 2 missense, 3 splice site, and 2 frameshift. Four previously reported variants were identified in >5% of unrelated families. There was a correlation with age and presence (p = 0.003) and severity (p = 0.002) of epilepsy and with obsessive-compulsive disorder (OCD) (p = 0.016). The median IQ score was 53 (Q25-Q75, 49-61). There was no overall correlation between the gene variants and the CSS, although a novel missense variant was associated with the mildest phenotype by CSS in the only patient with a normal IQ, whereas a previously reported variant was consistently associated with the most severe phenotype. CONCLUSIONS: Seven novel pathogenic and one previously unpublished benign ALDH5A1 variants were detected. There is an age-dependent association with worsening of epilepsy and presence of OCD in SSADH deficiency. Overall, there does not appear to be a correlation between genotype and phenotypic severity in this cohort of 24 patients. We did find a suspected correlation between a novel pathogenic missense variant and high functionality, and a previously reported pathogenic missense variant and maximal severity.

Comprehending reflexive and clitic constructions in children with autism spectrum disorder and developmental language disorder.

BACKGROUND: It has been established that people with autism spectrum disorder (ASD) often have difficulties understanding spoken language. Understanding reflexive and clitic pronouns is vital to establishing reference-based inference, but it is as yet unclear whether such constructions pose specific difficulties for those with ASD. Pronoun interpretation seems be connected to the development of pragmatic abilities, and can therefore be considered a plausible marker in the differential diagnosis between ASD and developmental language disorder (DLD). AIMS: To establish whether or not there are differences between ASD and DLD in relation to their understanding of pronoun constructions (both reflexive and clitic). The working hypothesis was that although no differences were expected between groups in relation to automatic (online) pronoun processing, the comprehension of reflexive pronouns would constitute a diagnostic marker between the group with ASD and language disorder and the DLD group. METHODS & PROCEDURES: The study carried out two experiments with three clinical groups (two with ASD and different levels of language proficiency and one with DLD) and two control groups with typically developing people (with equivalent language levels), analysing their on- and offline processing in pronoun resolution tasks. The first experiment uses an online method (eye-tracking) to record pronoun processing in real time. The second uses an offline method to analyse comprehension accuracy. OUTCOMES & RESULTS: The results of the two experiments indicated no differences in the way in which the clinical and control groups resolved the tasks, but a shorter reaction time was observed only in the age-matched control group in comparison with the ASD group without language disorder in the first experiment, perhaps due to the fact that processing pronouns involves a greater cognitive load among the latter group. CONCLUSIONS & IMPLICATIONS: The comprehension of reflexive pronouns cannot be considered a diagnostic marker for distinguishing ASD from DLD. What this paper adds What is already known on the subject Previous studies have found that the performance of children with ASD in the comprehension of personal pronouns is equivalent to youngest control groups, but poorer regarding the interpretation of reflective pronouns. However, children with DLD do not usually have problems with the use of pronouns, which suggests that their pronoun processing is not affected. As pronoun interpretation seems be connected to the development of pragmatic abilities, it could be considered a plausible marker in the differential diagnosis between ASD and DLD. What this paper adds to existing knowledge This paper presents the results of two experiments involving pronoun processing by those with ASD (both with and without language disorder) and those with DLD. The design enables us to analyse the reflexive and clitic pronoun processing in people with ASD and DLD, regardless of their language proficiency. One experiment uses an eye-tracking methodology that allows us to obtain data about how the pronouns are processed in real time. It represents an attempt to identify language markers that may help distinguish between the two groups and adapt the interventions to the specific problems experienced by each one. What are the potential or actual clinical implications of this work? The results indicate that it is not possible to identify any specific impairment in pronoun processing among the clinical groups (ASD and DLD).

A prospective observational study of developmental outcomes in survivors of neonatal hypoxic ischaemic encephalopathy in South Africa.

BACKGROUND: Neonatal hypoxic ischaemic encephalopathy (NHIE) is an important cause of long-term handicap in survivors. There is limited information on the burden of handicap from NHIE in sub-Saharan Africa. OBJECTIVES: To determine the developmental outcomes in survivors of NHIE in South Africa (SA). METHODS: In this prospective observational study, the developmental outcomes in 84 infants who had survived hypoxic ischaemic encephalopathy (the NHIE group) were compared with those in 64 unaffected infants (the control group). The Bayley Scales of Infant Development version III were used for assessment of developmental outcomes. RESULTS: Significant differences were found between the developmental outcomes of the two groups, with a significantly lower composite language score and higher proportions with language, motor and cognitive developmental delays in the NHIE group than in the control group. Cerebral palsy (CP) was present in 13 of the infants with NHIE (15.5%) and none in the control group (p<0.001). CP was associated with developmental delay, and also with the severity of NHIE. Therapeutic hypothermia (TH) was administered in 58.3% of the study group, but although it was associated with lower rates of CP and developmental delay than in the group without TH, the only significant difference was for delay on the language subscale. CONCLUSIONS: Survivors of NHIE in SA are at risk of poor developmental outcomes.

Feasibility of objective assessment of difference limen for intensity using acoustic change complex in children with central auditory processing disorder.

INTRODUCTION: Acoustic change complex (ACC) shows brain's ability to discriminate between acoustic features in an ongoing stimulus. It is this nature of ACC that has generated interest in studying the usefulness of ACC as an objective tool for evaluating difference limens for various stimulus parameters. The present study therefore aimed at investigating the utility of ACC as an objective measure of difference limen for intensity (DLI) in normal hearing children with and without (C)APD. METHODS: Fifteen children with (C)APD and 15 normal hearing children in whom (C)APD was ruled out (comparison group) in the age range of 8-12 years underwent ACC for 6 intensity differences (+1, +3, +4, +5, +10 & +20 dB) and a standard stimulus using a 1000 Hz stimulus. RESULTS: Behavioral DLI (DLIb) as well as DLI found using ACC (DLIo) were both significantly larger in children with (C)APD than the comparison group (p < 0.05). Further, there was a significantly strong positive correlation between DLIb and DLIo (p < 0.001]. CONCLUSION: Outcome of the study provides evidence for the clinical use of ACC as an objective tool for examining DLI in children with (C)APD.