Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis: a nationwide retrospective study

<p>Abstract</p> <p>Background</p> <p>Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions.</p> <p>Methods</p> <p>A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response.</p> <p>Results</p> <p>The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m²was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events.</p> <p>Conclusion</p> <p>VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.</p

Epilepsy with migrating focal seizures

To report new sporadic cases and 1 family with epilepsy of infancy with migrating focal seizures (EIMFSs) due to KCNT1 gain-of-function and to assess therapies' efficacy including quinidine. We reviewed the clinical, EEG, and molecular data of 17 new patients with EIMFS and KCNT1 mutations, in collaboration with the network of the French reference center for rare epilepsies. The mean seizure onset age was 1 month (range: 1 hour to 4 months), and all children had focal motor seizures with autonomic signs and migrating ictal pattern on EEG. Three children also had infantile spasms and hypsarrhythmia. The identified KCNT1 variants clustered as "hot spots" on the C-terminal domain, and all mutations occurred de novo except the p.R398Q mutation inherited from the father with nocturnal frontal lobe epilepsy, present in 2 paternal uncles, one being asymptomatic and the other with single tonic-clonic seizure. In 1 patient with EIMFS, we identified the p.R1106Q mutation associated with Brugada syndrome and saw no abnormality in cardiac rhythm. Quinidine was well tolerated when administered to 2 and 4-year-old patients but did not reduce seizure frequency. The majority of the KCNT1 mutations appear to cluster in hot spots essential for the channel activity. A same mutation can be linked to a spectrum of conditions ranging from EMFSI to asymptomatic carrier, even in the same family. None of the antiepileptic therapies displayed clinical efficacy, including quinidine in 2 patients

Rôle du médecin généraliste dans le dépistage et la prise en charge des troubles de l'acquisition du langage oral chez l'enfant (réalisation d'une enquête de faisabilité auprès des médecins généralistes d'un test de dépistage le ERTL 4)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

What do monolingual and bilingual children with and without SLI produce when phonology is too complex?

International audienceIn this study, the authors compare the production of internal codas and branching onsets in four groups of children learning French: monolingual typically-developing children (n = 12), bilingual typically-developing children (n = 61), monolingual children with Specific Language Impairment (n = 17) and bilingual children with Specific Language Impairment (n = 20). Their elicited productions were collected using a nonword repetition task (LITMUS-NWR-French), containing 71 nonwords with different syllable types. Except for typically-developing monolingual children, all children performed significantly better on branching onsets than on internal codas. Moreover, the repair strategies used in erroneous productions also indicate that children had more difficulties with internal codas: all the cases of metathesis affecting a target internal coda resulted in the production of a branching onset whereas the contrary was not observed. The differences in the rates of target-like production and the patterns of metathesis of these two structures suggest that internal codas are more difficult than branching onsets for children learning French

Pragmatic versus structural difficulties in the production of pronominal clitics in French-speaking children with autism spectrum disorder

Background and aims Impaired production of third person accusative pronominal clitics is a signature of language impairment in French-speaking children. It has been found to be a prominent and persistent difficulty in children and adolescents with specific language impairment. Previous studies have reported that many children with autism spectrum disorder also have low performance on these clitics. However, it remains unclear whether these difficulties in children with autism spectrum disorder are due to structural language impairment or to pragmatic deficits. This is because pragmatics skills, notoriously weak in children with autism spectrum disorder, are also needed for appropriate use of pronouns. Use of pronouns without clear referents and difficulty with discourse pronouns (first and second person), which require taking into account the point of view of one’s interlocutor (perspective shifting), have frequently been reported for autism spectrum disorder. Methods We elicited production of nominative, reflexive and accusative third and first person pronominal clitics in 19 verbal children with autism spectrum disorder (aged 6–12, high and low functioning, with structural language impairment, or with normal language) and 19 age-matched children with specific language impairment. If pragmatics is behind difficulties on these elements, performance on first-person clitics would be expected to be worse than performance on third person clitics, since it requires perspective shifting. Furthermore, worse performance for first person clitics was expected in the children with autism spectrum disorder compared to the children with specific language impairment, since weak pragmatics is an integral part of impairment in the former, but not in the latter. More generally, different error patterns would be expected in the two groups, if the source of difficulty with clitics is different (a pragmatic deficit vs. a structural language deficit). Results Similar patterns of relative difficulties were found in the autism spectrum disorder language impairment and specific language impairment groups, with third person accusative clitics being produced at lower rates than first-person pronouns and error patterns being essentially identical. First-person pronouns did not pose particular difficulties in the children with autism spectrum disorder (language impairment or normal language) with respect to third-person pronouns or to the children with specific language impairment. Performance was not related to nonverbal intelligence in the autism spectrum disorder group. Conclusions The elicitation task used in this study included explicit instruction, and focus on perspective shifting (both visual and verbal), allowing for potential pragmatic effects to be controlled. Moreover, the task elicited a variety of types of clitics in morphosyntactic contexts of varying complexity, providing ample opportunities for employment of perspective shifting, which may have also curtailed perseveration of third person over first person. These properties of the task allowed for the grammatical nature of children’s difficulties with third-person accusative clitics to emerge unambiguously. Implications Assessment of structural language abilities in children with autism spectrum disorder requires careful consideration of task demands. The influence of pragmatic abilities on structural language performance can be circumvented by making the pragmatic demands of the task explicit and salient. Filtering out this potential influence on structural language performance is fundamental to understanding language profiles in children with autism spectrum disorder and thus which children could benefit from which kinds of language intervention