Differences and Commonalities in Children with Childhood Apraxia of Speech and Comorbid Neurodevelopmental Disorders: A Multidimensional Perspective.

Childhood apraxia of speech (CAS) is a motor speech disorder often co-occurring with language impairment and complex neurodevelopmental disorders. A cohort of 106 children with CAS associated to other neurodevelopmental disorders underwent a multidimensional investigation of speech and language profiles, chromosome microarray analysis and structural brain magnetic resonance (MR). Our aim was to compare the clinical profiles of children with CAS co-occurring with only language impairment with those who, in addition to language impairment, had other neurodevelopmental disorders. Expressive grammar was impaired in the majority of the sample in the context of similar alterations of speech, typical of the core symptoms of CAS. Moreover, children with complex comorbidities also showed more severe and persistent receptive language deficits. About 25% of the participants harbored copy number variations (CNVs) already described in association to neurodevelopmental disorders. CNVs occurred more frequently in children with complex comorbidities. MR structural/signal alterations were found in a small number of children and were of uncertain pathogenic significance. These results confirm that CAS needs multidimensional diagnostic and clinical management. The high frequency of language impairment has important implications for early care and demands a personalized treatment approach in which speech and language goals are consistently integrated.

Cerebral lateralization for language in deaf children with cochlear implantation.

Functional Transcranial Doppler ultrasonography (fTCD) was used to investigate the effects of early acoustic deprivation and subsequent reafferentation on cerebral dominance for language in deaf children provided with Cochlear Implantation (CI). Twenty children with CI (13 in right ear and 7 in left ear) and 20 controls matched for age, sex and handedness were administered a fTCD animation description task. Left hemisphere dominance for language with comparable mean Laterality Indexes (LIs) was found in children with CI and controls; right-ear implanted subjects showed cerebral activation controlateral to implanted ear more frequently than left-ear implanted ones. Linguistic proficiency of CI recipients was below age expectation in comparison to controls; language scores did not significantly differ between children with left and right LI, whereas both age and side of implantation were significantly related to language outcome. Theoretical implication and potential clinical application of fTCD in CI management are discussed.

A longitudinal study of lexical and grammar development in deaf Italian children provided with early cochlear implantation.

OBJECTIVE: A growing number of studies on deaf children with cochlear implant (CI) document a significant improvement in receptive and expressive language skills after implantation, even if they show language delay when compared with normal-hearing peers. Data on language acquisition in CI Italian children are still scarce and limited to only certain aspects of language. The purpose of this study is to prospectively describe the trajectories of language development in early CI Italian children, with particular attention to the transition from first words to combinatorial speech and to acquisition of complex grammar in a language with rich morphology, such as Italian. DESIGN: Six children, with profound prelingual deafness, provided with CI, between 16 and 24 months of age were prospectively assessed and followed over a mean period of up to 34.8 months postimplant. During follow-up, each child received between four to five individual language evaluations through a combination of indirect procedures (parent reports of early lexical and grammar development) and direct ones (administration of standardized receptive and expressive language tests with Italian norms and collection of spontaneous language samples). RESULTS: In relation to chronological age, the acquisition of expressive vocabulary was delayed. However, considering the duration of hearing experience, most CI participants showed an earlier start and faster growth of expressive rather than receptive vocabulary in comparison with typically developing children. This quite atypical result persisted right up until the end of the follow-up. The acquisition of expressive grammar was delayed relative to chronological age, though all but one CI participant achieved the expected grammar level after approximately 3 years of CI use. In addition, the rate of grammar acquisition was not homogeneous during development, showing two different paces: one comparable with normal hearing in the transition from holophrastic to primitive combinatorial speech and a much slower one to attain more advanced levels of morphosyntactic control. CONCLUSION: From a rehabilitative viewpoint, our results suggest the importance of implementing rehabilitation in lexical comprehension, even when expressive vocabulary appears to be within normal range. Moreover, assessment of language acquisition in CI Italian children should focus on those grammar aspects that are more vulnerable to early acoustic deprivation (such as free and bound morphology) to ensure enhanced language therapy planning.

Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency.

BACKGROUND: SLC6A8, an X-linked gene, encodes the creatine transporter (CRTR) and its mutations lead to cerebral creatine (Cr) deficiency which results in mental retardation, speech and language delay, autistic-like behaviour and epilepsy (CRTR-D, OMIM 300352). CRTR-D represents the most frequent Cr metabolism disorder but, differently from Cr synthesis defects, that are partially reversible by oral Cr supplementation, does not respond to Cr treatment even if precociously administrated. The precursors of Cr are the non-essential amino acids Glycine (Gly) and Arginine (Arg), which have their own transporters at the brain-blood barrier level and, therefore, their supplementation appears an attractive and feasible therapeutic option aimed at stimulating Cr endogenous synthesis and, in this way, at overcoming the block of Cr transport within the brain. However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial. METHODS: In this study five Italian male patients affected by CRTR-D were supplemented with oral L-Arg at a dosage of 300 mg/kg/day divided into 3 doses, for 24-36 months. Biochemical and plasmatic amino acids examinations and thyroid hormone dosages were periodically performed. Moreover, Proton and Phosphorus Magnetic Resonance Spectroscopy (MRS) was monitored during follow-up in concurrence with neuropsychological evaluations. RESULTS: During L-Arg treatment a clinical improvement in motor skills and to a lesser extent in communication and attention was observed. In addition, all patients had a reduction in the number and frequency of epileptic seizures. Daily living skills appeared also to be positively influenced by L-Arg treatment. Moreover, Total Cr and especially PhosphoCr, evaluated by proton and phosphorus spectroscopy, showed a mild increase, although well below the normal range. CONCLUSION: This study provides information to support the effectiveness of L-Arg supplement treatment in CTRT-D patients; in fact the syndromic pattern of cognitive and linguistic deficit presented by CRTR-D patients was partially altered by L-Arg supplementation especially at a qualitative clinical level. Oral L-Arg may represent not only a protective factor towards a further cognitive decline, but can lead to the acquisition of new skills.

Neurodevelopmental disorders in children with severe to profound sensorineural hearing loss: a clinical study.

AIM: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation between these additional disabilities and the aetiology of deafness. METHOD: One hundred children with severe/profound SNHL (60 males, 40 females; mean age 5 y 7 mo, SD 3 y 6 mo, range 8 mo-16 y) were investigated using a diagnostic protocol including neurodevelopmental, genetic, neurometabolic, and brain magnetic resonance imaging (MRI) assessment. RESULTS: Forty-eight per cent of the sample exhibited one or more additional disabilities, with cognitive, behavioural-emotional, and motor disorders being the most frequent. The risk of additional disabilities varied according to the type of aetiology. Thirty-seven out of 80 individuals with available MRIs showed signal abnormalities, in particular brain malformations (46%) and white matter abnormalities (54%). Frequency and type of disability were associated with aetiology (p=0.015) and MRI data (p<0.001). INTERPRETATION: A multidimensional evaluation, including aetiological, neurodevelopmental, and MRI investigation, is needed for planning therapeutic intervention, such as cochlear implantation in children with severe to profound hearing impairment. The aetiology of deafness is a relevant risk indicator for the presence of an associated disorder.

Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect.

Creatine transporter deficit (CT1) is an inherited metabolic disorder that causes mental retardation, epilepsy, speech, language and behavioral deficits. Until now, no treatment has been proven to be successful for this condition. We describe 1-year follow-up study of a child, aged 9.6 years, with CT1 defect, on oral supplementation with L-arginine, a precursor of creatine synthesis. Under supplementation, he showed a noticeable improvement of neurological, language and behavioral status and an increase of brain creatine and phosphocreatine documented with magnetic resonance spectroscopy. The results suggest that children with CT1 disorder show some residual adaptive plasticity for certain functions even at quite an advanced age. Further trials with higher L-arginine dosages and more protracted treatment are encouraged.