Ceroid lipofuscinosis type 2 disease: Effective presymptomatic therapy-Oldest case of a presymptomatic enzyme therapy.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the TPP1 gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical TPP1 variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle-term treatment benefit for patients with CLN2.

The Magnitude of Contralateral Suppression of Otoacoustic Emissions Is Ear- and Age-Dependent.

The maturation of the uncrossed medial olivocochlear (UMOC) efferent remains poorly documented to date. The UMOC efferent system allows listeners to not only detect but also to process, recognize, and discriminate auditory stimuli. Its fibers can be explored non-invasively by recording the effect of contralateral acoustic stimulation (CAS), resulting in a decrease in the amplitude of transient evoked otoacoustic emissions (TEOAE). The objective of the present cross-sectional study was to investigate how the effectiveness of this system varies with age in healthy subjects aged 8 years to adulthood. For this purpose, 120 right-handed native French-speaking subjects (57 females and 63 males) were divided into five age groups of 24 subjects each: 8y-10y, 10y-11y6m, 11y6m-13y, 13y-17y, and ≥18y. TEOAE amplitudes with and without CAS were recorded. The equivalent attenuation (EA) was calculated, corresponding to the change in TEOAE amplitude equivalent to the effect generated by CAS. General linear models were performed to control for the effect of ear, sex, and age on EA. No sex effect was found. A stronger EA was consistently found regardless of age group in the right ear compared to the left. In contrast to the right ear, for which, on average, EA remained constant across age groups, an increasingly weaker TEOAE suppression effect with age was found in the left ear, reinforcing the asymmetrical functioning of the UMOC efferent system in favor of the right ear in adulthood. Further studies are needed to investigate the lateralization of the UMOC efferent system and its changes over time in cases of atypical or reversed cortical asymmetries, especially in subjects with specific learning disorders.

Early grammar-building in French-speaking deaf children with cochlear implants: A follow-up corpus study.

BACKGROUND: One of the most consistent findings reported in the paediatric cochlear implant (CI) literature is the heterogeneity of language performance observed more in grammatical morphology than in lexicon or pragmatics. As most of the corpus studies addressing these issues have been conducted in English, it is unclear whether their results can be generalized to other languages. In particular, little is known about languages known for their grammatical complexity, such as French. AIMS: The aim of this corpus study was to compare the productive use of function words (FWs) and some agreement features (AGRs) in children with CIs and children with typical development (TD) matched for mean length of utterance in words (MLUwords ), a general index of grammatical complexity, and auditory experience, as measured by hearing age (HA) and chronological age (CA), respectively. METHODS & PROCEDURES: Natural speech samples from 116 monolingual French-speaking children, including 40 children with CIs followed longitudinally and 76 TD children, were collected. FWs and AGRs were analysed using a Part of Speech Tagger (POS-T) from the Child Language Data Exchange System (CHILDES). OUTCOMES & RESULTS: The two groups differed by 3 years for HA and CA. No effect of family socio-economic status (SES) was found in the CI group. Stepwise regression analyses showed that the two groups did not share the same predictors of MLUwords : plurals and determiners predicted MLUwords in children with CIs, at 2 and 3 years of HA, whereas feminine markers and subject-pronouns were found to best predict MLUwords in TD children at 2 and 3 years of CA. Structural equation models (SEMs), a combination of confirmatory factor analysis (CFA) and path analysis, yielded a different hierarchical structure of grammatical relations (GRs). Selective difficulties affecting verbal clitics and other pronominal forms were found specifically in the CI group (object-pronouns, reflexive, relative and past participles). Dependency grammar analysis confirmed these contrasting developmental profiles in multiword utterances, such as preposition/nouns, subject/verbs, and verb/determiner/nouns. CONCLUSIONS & IMPLICATIONS: Atypical grammatical patterns in children with CIs reflect a specific architecture of syntactic dependencies of FWs underpinning morphological complexity and syntactic connectivity. Clinical implications are discussed for assessment and intervention planning. WHAT THIS PAPER ADDS: What is already known on this subject The productive use of FWs has been identified as a particular area of weakness in children with CIs compared with TD children. In addition, heterogenous grammatical performance has often been found after 1-3 years of CI use, regardless of demographic factors such as age at implantation, duration of deafness or SES. What this paper adds to existing knowledge Assessing the early building of FWs and AGRs in children with CIs helps to understand the syntactic complexity and hierarchical structure of their language. Since most corpus studies on grammatical morphology have been conducted in English, it is not clear whether their difficulties can be generalized to other languages. The French language has a system of FWs and inflections that determine the morphophonological properties of nominal and verbal forms. Early grammar learning in children with CIs born with profound deafness were compared with the two groups of TD children matched both for duration of auditory experience (i.e., HA of CI children, CA of TD children) and for MLUwords . We found a similar profile between groups at 2 years but not at 3 years for HA and CA. The two groups do not share the same predictors of MLUwords : namely, plurals and determiners for CI children versus feminine markers and subject pronouns for TD children. They show a different syntactic organization of GRs. Children with CIs struggle with selective difficulties affecting verbal clitics and pronominal forms (object-pronouns, reflexive, relative and past participles). Consistent with theories of morphophonological richness and syntactic connectivity, our results support the distributional learning hypothesis of language acquisition that infants and toddlers are sensitive to FWs and AGRs at an early age. Specific components of syntactic organization are disrupted in children with CIs. What are the potential or actual clinical implications of this work? This work has potential clinical implications because it unravels the limitations of morphophonological processing in children with CIs. Its results highlight a specific difficulty in learning FWs and AGRs in a verbal inflectional morphology context.

Age-Related Dichotic Listening Skills in Impaired and Non-Impaired Readers: A Comparative Study.

Dichotic listening is the high-level auditory process which enables the perception of different verbal stimuli delivered simultaneously to the right and left ears (binaural integration), as well as the perception of a verbal stimulus presented to one ear while ignoring a different stimulus in the other ear (binaural separation). Deficits in central auditory processing have been reported in children with learning disabilities. The present study aimed to compare dichotic listening performances in right-handed impaired readers (IR) and non-impaired readers (non-IR) according to age. For this, a cross-sectional study was conducted in 120 IR (56 males and 64 females) divided into five age groups and 120 non-IR (63 male and 57 female) matched on chronological age (8 to 9 years; 9 to 10 years; 10 to 12 years; 12 to 18 years; adult). They were tested for binaural integration and binaural separation, allowing for the calculation of dichotic aptitude (DA), ear prevalence (EP), and attentional shift index (ASI). A series of ANOVAs showed an effect of age and of the reading group for all the dichotic-related measures, except for EP. Binaural separation scores were lower in IR who also showed more intrusive responses compared to non-IR. These intrusive responses, which were more frequent on the right ear for IR, decreased with age in both groups. Overall, these results suggest that dichotic listening scores improve with age as the central auditory pathways mature. However, whatever the age, performances are lower in IR than in non-IR. This might be explained by an incomplete maturation of the auditory pathways in IR; an early start for long-term follow-up and auditory training is suggested.

The role of Function Words to build syntactic knowledge in French-speaking children.

The question of how children learn Function Words (FWs) is still a matter of debate among child language researchers. Are early multiword utterances based on lexically specific patterns or rather abstract grammatical relations? In this corpus study, we analyzed FWs having a highly predictable distribution in relation to Mean Length Utterance (MLU) an index of syntactic complexity in a large naturalistic sample of 315 monolingual French children aged 2 to 4 year-old. The data was annotated with a Part Of Speech Tagger (POS-T), belonging to computational tools from CHILDES. While eighteen FWs strongly correlated with MLU expressed either in word or in morpheme, stepwise regression analyses showed that subject pronouns predicted MLU. Factor analysis yielded a bifactor hierarchical model: The first factor loaded sixteen FWs among which eight had a strong developmental weight (third person singular verbs, subject pronouns, articles, auxiliary verbs, prepositions, modals, demonstrative pronouns and plural markers), whereas the second factor loaded complex FWs (possessive verbs and object pronouns). These findings challenge the lexicalist account and support the view that children learn grammatical forms as a complex system based on early instead of late structure building. Children may acquire FWs as combining words and build syntactic knowledge as a complex abstract system which is not innate but learned from multiple word input sentences context. Notably, FWs were found to predict syntactic development and sentence complexity. These results open up new perspectives for clinical assessment and intervention.

Simplification of syllable structure in childhood apraxia of speech: a 2-year follow-up French case study.

Although Childhood Apraxia of Speech (CAS) has been extensively investigated in the clinical literature, most of the findings regarding impairments in the production of syllable structure, recorded within this population, have been mainly focused on English. The main purpose of this two-year follow-up case study was, therefore, to examine whether syllable complexity may be considered as a robust indicator in CAS and whether it can explain the persistence of errors and, if so, at what age. This was tested in a boy followed up annually from age 5 to 7 who was administered a narrative task. Data analyses used the Phon program to estimate accuracies of different syllabic structures, phones, singleton and cluster consonants. Overall, the findings suggest that this child experienced difficulty producing syllabic structure commensurately with the level of complexity of the target structures. Notably, the presence of syllable planning/sequencing deficit found in French data clearly supports the hypotheses according to which (a) there is a relationship between the level of complexity of syllabic structures and their simplification and (b) the persistence of errors on the most complex syllables remains, becoming a robust indicator for identifying CAS from other speech disorders. Further cross-language investigations on syllable complexity in CAS are needed to design better assessments and to plan efficient intervention.

Developmental Trajectories of Hand Movements in Typical Infants and Those at Risk of Developmental Disorders: An Observational Study of Kinematics during the First Year of Life.

Highlights The kinematics of hand movements (spatial use, curvature, acceleration, and velocity) of infants with their mothers in an interactive setting are significantly associated with age in cohorts of typical and at-risk infantsdiffer significantly at 5-6 months of age, depending on the context: relating either with an object or a person.Environmental and developmental factors shape the developmental trajectories of hand movements in different cohorts: environment for infants with VIMs; stage of development for premature infants and those with West syndrome; and both factors for infants with orality disorders.The curvature of hand movements specifically reflects atypical development in infants with West syndrome when developmental age is considered. We aimed to discriminate between typical and atypical developmental trajectory patterns of at-risk infants in an interactive setting in this observational and longitudinal study, with the assumption that hand movements (HM) reflect preverbal communication and its disorders. We examined the developmental trajectories of HM in five cohorts of at-risk infants and one control cohort, followed from ages 2 to 10 months: 25 West syndrome (WS), 13 preterm birth (PB), 16 orality disorder (OD), 14 with visually impaired mothers (VIM), 7 early hospitalization (EH), and 19 typically developing infants (TD). Video-recorded data were collected in three different structured interactive contexts. Descriptors of the hand motion were used to examine the extent to which HM were associated with age and cohort. We obtained four principal results: (i) the kinematics of HM (spatial use, curvature, acceleration, and velocity) were significantly associated with age in all cohorts; (ii) HM significantly differed at 5-6 months of age in TD infants, depending on the context; (iii) environmental and developmental factors shaped the developmental trajectories of HM in different cohorts: environment for VIM, development for PB and WS, and both factors for OD and; (iv) the curvatures of HM showed atypical development in WS infants when developmental age was considered. These findings support the importance of using kinematics of HM to identify very early developmental disorders in an interactive context and would allow early prevention and intervention for at-risk infants.

Disrupted behaviour in grammatical morphology in French speakers with autism spectrum disorders.

Mixed and inconsistent findings have been reported across languages concerning grammatical morphology in speakers with Autism Spectrum Disorders (ASD). Some researchers argue for a selective sparing of grammar whereas others claim to have identified grammatical deficits. The present study aimed to investigate this issue in 26 participants with ASD speaking European French who were matched on age, gender and SES to 26 participants with typical development (TD). The groups were compared regarding their productivity and accuracy of syntactic and agreement categories using the French MOR part-of-speech tagger available from the CHILDES. The groups significantly differed in productivity with respect to nouns, adjectives, determiners, prepositions and gender markers. Error analysis revealed that ASD speakers exhibited a disrupted behaviour in grammatical morphology. They made gender, tense and preposition errors and they omitted determiners and pronouns in nominal and verbal contexts. ASD speakers may have a reduced sensitivity to perceiving and processing the distributional structure of syntactic categories when producing grammatical morphemes and agreement categories. The theoretical and cross-linguistic implications of these findings are discussed.

Acoustic Analyses of Prolonged Vowels in Young Adults With Friedreich Ataxia.

OBJECTIVES: Finding measures that track disease progression and determine treatment efficacy is vital for appropriate management in Friedreich ataxia (FA). The purpose of this study was to determine which cepstral- and spectral-based measures extracted from prolonged vowels using Analysis of Dysphonia in Speech and Voice (ADSV) program discriminate between those who have FA and normal voice (NV) peers. STUDY DESIGN: This is a descriptive, prospective study. METHODS: Initial 2 seconds of prolonged /a/, /i/, and /o/ were analyzed through ADSV from 20 individuals diagnosed with FA and 20 NV individuals. ADSV measures used were cepstral peak prominence (CPP), cepstral peak prominence standard deviation (CPP SD), low/high spectral ratio (L/H ratio), low/high spectral ratio standard deviation (L/H ratio SD), and the Cepstral/Spectral Index of Dysphonia (CSID). RESULTS: L/H ratio SD was the only measure where significant differences were found across all vowels between groups. Comparing measures per vowel, the vowel /o/ was significantly different between groups on four of five measures. Discrimination analysis revealed 100% of those in the FA group were classified correctly (sensitivity), whereas 95% of NV members were correctly identified (specificity) when all ADSV measures, with the exception of L/H ratio, were entered. CONCLUSIONS: Unstable periods of phonation, such as initiations of voice production in vowels, may yield robust acoustic cues in the FA population. ADSV provides measures that, when considered together, have excellent sensitivity and very good specificity. Vowels yielded differing results on ADSV measures; analysis of different vowel types is recommended.

Reliability of the Language ENvironment Analysis system (LENA™) in European French.

In this study, we examined the accuracy of the Language ENvironment Analysis (LENA) system in European French. LENA is a digital recording device with software that facilitates the collection and analysis of audio recordings from young children, providing automated measures of the speech overheard and produced by the child. Eighteen native French-speaking children, who were divided into six age groups ranging from 3 to 48 months old, were recorded about 10-16 h per day, three days a week. A total of 324 samples (six 10-min chunks of recordings) were selected and then transcribed according to the CHAT format. Simple and mixed linear models between the LENA and human adult word count (AWC) and child vocalization count (CVC) estimates were performed, to determine to what extent the automatic and the human methods agreed. Both the AWC and CVC estimates were very reliable (r = .64 and .71, respectively) for the 324 samples. When controlling the random factors of participants and recordings, 1 h was sufficient to obtain a reliable sample. It was, however, found that two age groups (7-12 months and 13-18 months) had a significant effect on the AWC data and that the second day of recording had a significant effect on the CVC data. When noise-related factors were added to the model, only a significant effect of signal-to-noise ratio was found on the AWC data. All of these findings and their clinical implications are discussed, providing strong support for the reliability of LENA in French.

Rhythm reproduction in kindergarten, reading performance at second grade, and developmental dyslexia theories.

Temporal processing deficit could be associated with a specific difficulty in learning to read. In 1951, Stambak provided preliminary evidence that children with dyslexia performed less well than good readers in reproduction of 21 rhythmic patterns. Stambak's task was administered to 1,028 French children aged 5-6 years. The score distribution (from 0 to 21) was quasi-normal, with some children failing completely and other performing perfectly. In second grade, reading was assessed in 695 of these children. Kindergarten variables explained 26% of the variance of the reading score at second grade. The Stambak score was strongly and linearly related to reading performance in second grade, after partialling out performance on other tasks (oral repetition, attention, and visuo-spatial tasks) and socio-cultural level. Findings are discussed in relation to perceptual, cerebellar, intermodal, and attention-related theories of developmental dyslexia. It is concluded that simple rhythm reproduction tasks in kindergarten are predictive of later reading performance.

Lexical diversity and productivity in French preschoolers: developmental, gender and sociocultural factors.

In this study, we examined the influence of child gender and sociocultural (SCL) factors in language production. Subjects were French Parisian children in nine age groups (24, 27, 30, 33, 36, 39, 42, 45 and 48 months). A total of 316 language samples were recorded during a 20-min standardized play session. Measures of grammatical and lexical development included Mean Length of Utterance (MLU) and word type and token - specifically, grammatical words such as determiners, prepositions and pronouns as well as verbs. ANOVAs revealed strong influences of SCL, with children from high SCL families showing more complex lexical productions and a higher rate of development. These observations suggest that amount of exposure to language accounts for this differential rate of acquisition. Analyses also revealed a general effect of gender, showing a small advantage in language production for girls over boys until 36 months of age.

[Oral and written language production in prematures children: results in 7 1/2-year-old]. / Langage oral et écrit chez des enfants prématurés: résultats à 7(1/2) ans.

Prematurity entails risk factors of cognitive delay, particularly in language production and reading. These risk factors may be related to physiological and/or environmental variables. This study has two main objectives: (1) to track down which preterm children are most at risk of developing cognitive delays, particularly language production and reading; (2) to study whether screening of oral language in 3 1/2-year-olds predicts their future reading ability. A cohort of 50 pre-term children (23 boys and 27 girls) was followed from the ages of 2 to 7 1/2 years. The results show that: (a) 28% of the premature children present delayed language production at 3 1/2 years of age; (b) 34% of these children present delayed reading at 7 1/2 years of age; (c) language production at 3 1/2 years predicts the reading ability at 7 1/2 years, and (d) premature children who are most at risk are those who belong to low sociocultural groups.

Production of lexical categories in French children with SLI and in normally developing children matched for MLU.

Free speech recording samples of two groups of French SLI children aged 48 and 62 months (matched for MLU, 1.70) and two groups of French normally developing children aged 26 and 36 month (matched for MLU, 3.2) were compared to determine whether they showed a difference in the use of lexical categories. A category-by-category comparison showed few significant differences. For low MLU children, SLI produced significantly fewer infinitives, past participles, copulas, and demonstrative pronouns. For high MLU children, the difference persisted only in past participles use. As for English SLI children, French SLI children were delayed in their acquisition of verbs. However, the differences in the syntactic structure of English and French ruled out a syntactic explanation of the deficit. Phonetic problems seem to decrease with age, so they cannot be the only explanation behind the difficulties of SLI children, which probably involve cognitive problems such as processing limitations.