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For many encephalitis cases, the cause remains unidentified. After 2 children (from the same family) received a diagnosis of acute necrotizing encephalopathy at Centre Hospitalier Universitaire (Tours, France), we attempted to identify the etiologic agent. Because clinical samples from the 2 patients were negative for all pathogens tested, urine and throat swab specimens were added to epithelial cells, and virus isolates detected were characterized by molecular analysis and electron microscopy. We identified a novel reovirus strain (serotype 2), MRV2Tou05, which seems to be closely related to porcine and human strains. A specific antibody response directed against this new reovirus strain was observed in convalescent-phase serum specimens from the patients, whereas no response was observed in 38 serum specimens from 38 healthy adults. This novel reovirus is a new etiologic agent of encephalitis. [ABSTRACT FROM AUTHOR]

Abstract Background 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. Methods 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. Results The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m2 was 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. Conclusion 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.

Objective: Complex epilepsies such as epileptic and developmental encephalopathies require multidisciplinary care throughout life. A coordinated transition program is therefore essential to provide optimal support for patients leaving pediatric for adult care. The aim of this study is to describe and evaluate our transition program for complex epilepsies, focusing on the last step in this program, that is, the multidisciplinary transition day hospital (MTDH)., Methods: We performed a retrospective observational study including patients with complex epilepsies who underwent the full steps of the transition program at Necker-Enfants Malades Hospital between May 2021 and June 2023, with a follow-up until February 2024. We described the cohort and detailed the interventions performed during the MTDH including medical, medicosocial, educational, daily life abilities, and laboratory and imaging assessments with the participation of one member of the adult team. We evaluated two indicators of our program: (1) the "adult first clinic attendance rate," defined by the percentage of patients attending their first adult clinic; and (2) the "return rate," defined by the percentage of patients who requested a pediatric encounter after their transfer., Results: Our cohort included 70 patients with a mean age of 19.1 years (interquartile range = 16.3-19.5). Eighty percent had an epilepsy syndrome diagnosis; 72.8% were treated with three or more antiseizure medications. All patients had their appointment at the adult clinic within 6 months of the day hospital, and only two families requested a pediatric encounter after the transfer., Significance: The transition program is key for an optimal transfer of patients with complex epilepsies to adult care. It requires a comprehensive multidisciplinary approach and provides a complete summary of the medical record. Our program secures a smooth landing in adult care and is a promising model to better manage the challenging transition process, especially in patients with complex epilepsy., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: To characterize the electro-clinical presentation of patients with pyridoxine-dependent epilepsy (PDE) and pyridoxal phosphate (PLP)-dependent epilepsy in order to determine whether some of them could be diagnosed as de novo West syndrome, i. e., West syndrome that starts after the age of 2 months without other types of seizures (focal seizures for instance) before the onset of epileptic spasms. Methods: We analyzed data from an unpublished cohort of 28 genetically confirmed cases of PDE with antiquitine (ATQ) deficiency and performed a review of the literature looking for description of West syndrome in patients with either PDE with ATQ deficiency or PLP-dependent epilepsy with Pyridox(am)ine phosphate oxidase (PNPO) deficiency. Results: Of the 28 cases from the ATQ deficiency French cohort, 5 had spasms. In four cases, spasms were associated with other types of seizures (myoclonus, focal seizures). In the last case, seizures started on the day of birth. None of these cases corresponded to de novo West syndrome. The review of the literature found only one case of PNPO deficiency presenting as de novo West syndrome and no case of ATQ deficiency. Significance: The presentation of PDE- and PLP-dependent epilepsy as de novo West syndrome is so exceptional that it probably does not justify a systematic trial of pyridoxine or PLP. We propose considering a therapeutic trial with these vitamins in West syndrome if spasms are associated with other seizure types or start before the age of 2 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gibaud, Barth, Lefranc, Mention, Villeneuve, Schiff, Maurey, Barthez, Caubel, Chouchane, Doummar, Kossorotoff, Lamblin, Roubertie, Nabbout and Van Bogaert.)

Objective: To perform genotype-phenotype, clinical and molecular analysis in a large 3-generation family with autosomal dominant congenital spinal muscular atrophy., Methods: Using a combined genetic approach including whole genome scanning, next generation sequencing-based multigene panel, whole genome sequencing, and targeted variant Sanger sequencing, we studied the proband and multiple affected individuals of this family who presented bilateral proximal lower limb muscle weakness and atrophy., Results: We identified a novel heterozygous variant, c.1826T > C; p.Ile609Thr, in the DYNC1H1 gene localized within the common haplotype in the 14q32.3 chromosomal region which cosegregated with disease in this large family. Within the family, affected individuals were found to have a wide array of clinical variability. Although some individuals presented the typical lower motor neuron phenotype with areflexia and denervation, others presented with muscle weakness and atrophy, hyperreflexia, and absence of denervation suggesting a predominant upper motor neuron disease. In addition, some affected individuals presented with an intermediate phenotype characterized by hyperreflexia and denervation, expressing a combination of lower and upper motor neuron defects., Conclusion: Our study demonstrates the wide clinical variability associated with a single disease causing variant in DYNC1H1 gene and this variant demonstrated a high penetrance within this large family., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To assess nonparoxysmal movement disorders in ATP1A3 mutation-positive patients with alternating hemiplegia of childhood (AHC)., Methods: Twenty-eight patients underwent neurologic examination with particular focus on movement phenomenology by a specialist in movement disorders. Video recordings were reviewed by another movement disorders specialist and data were correlated with patients' characteristics., Results: Ten patients were diagnosed with chorea, 16 with dystonia (nonparoxysmal), 4 with myoclonus, and 2 with ataxia. Nine patients had more than one movement disorder and 8 patients had none. The degree of movement disorder was moderate to severe in 12/28 patients. At inclusion, dystonic patients (n = 16) were older ( p = 0.007) than nondystonic patients. Moreover, patients (n = 18) with dystonia or chorea, or both, had earlier disease onset ( p = 0.042) and more severe neurologic impairment ( p = 0.012), but this did not correlate with genotype. All patients presented with hypotonia, which was characterized as moderate or severe in 16/28. Patients with dystonia or chorea (n = 18) had more pronounced hypotonia ( p = 0.011). Bradykinesia (n = 16) was associated with an early age at assessment ( p < 0.01). Significant dysarthria was diagnosed in 11/25 cases. A history of acute neurologic deterioration and further regression of motor function, typically after a stressful event, was reported in 7 patients., Conclusions: Despite the relatively limited number of patients and the cross-sectional nature of the study, this detailed categorization of movement disorders in patients with AHC offers valuable insight into their precise characterization. Further longitudinal studies on this topic are needed., (© 2020 American Academy of Neurology.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Epilepsy of infancy with migrating focal seizures was first described in 1995. Fifteen years later, KCNT1 gene mutations were identified as the major disease-causing gene of this disease. Currently, the data on epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations are heterogeneous and many questions remain unanswered including the prognosis and the long-term outcome especially regarding epilepsy, neurological and developmental status and the presence of microcephaly. The aim of this study was to assess data from patients with epilepsy in infancy with migrating focal seizures with KCNT1 mutations to refine the phenotype spectrum and the outcome. We used mind maps based on medical reports of children followed in the network of the French reference centre for rare epilepsies and we developed family surveys to assess the long-term outcome. Seventeen patients were included [age: median (25th-75th percentile): 4 (2-15) years, sex ratio: 1.4, length of follow-up: 4 (2-15) years]. Seventy-one per cent started at 6 (1-52) days with sporadic motor seizures (n = 12), increasing up to a stormy phase with long lasting migrating seizures at 57 (30-89) days. The others entered this stormy phase directly at 1 (1-23) day. Ten patients entered a consecutive phase at 1.3 (1-2.8) years where seizures persisted at least daily (n = 8), but presented different semiology: brief and hypertonic with a nocturnal (n = 6) and clustered (n = 6) aspects. Suppression interictal patterns were identified on the EEG in 71% of patients (n = 12) sometimes from the first EEG (n = 6). Three patients received quinidine without reported efficacy. Long-term outcome was poor with neurological sequelae and active epilepsy except for one patient who had an early and long-lasting seizure-free period. Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. Refining the electro-clinical characteristics and the temporal sequence of epilepsy in infancy with migrating focal seizures should help diagnosis of this epilepsy. A better knowledge of the outcome allows one to advise families and to define the appropriate follow-up and therapies. Extracerebral involvement should be investigated, in particular the cardiac system, as it may be involved in the high prevalence of sudden unexpected death in epilepsy in these cases., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To investigate the genetic basis of congenital ataxias (CAs), a unique group of cerebellar ataxias with a nonprogressive course, in 20 patients from consanguineous families, and to identify new CA genes., Methods: Singleton -exome sequencing on these 20 well-clinically characterized CA patients. We first checked for rare homozygous pathogenic variants, then, for variants from a list of genes known to be associated with CA or very early-onset ataxia, regardless of their mode of inheritance. Our replication cohort of 180 CA patients was used to validate the new CA genes., Results: We identified a causal gene in 16/20 families: six known CA genes (7 patients); four genes previously implicated in another neurological phenotype (7 patients); two new candidate genes (2 patients). Despite the consanguinity, 4/20 patients harbored a heterozygous de novo pathogenic variant., Conclusion: Singleton exome sequencing in 20 consanguineous CA families led to molecular diagnosis in 80% of cases. This study confirms the genetic heterogeneity of CA and identifies two new candidate genes (PIGS and SKOR2). Our work illustrates the diversity of the pathophysiological pathways in CA, and highlights the pathogenic link between some CA and early infantile epileptic encephalopathies related to the same genes (STXBP1, BRAT1, CACNA1A and CACNA2D2).

Pontocerebellar hypoplasias (PCH) are characterized by lack of development and/or early neurodegeneration of cerebellum and brainstem. We report five patients referred for PCH, showing atypical clinical and magnetic resonance imaging (MRI) features suggestive of defects in the Reelin pathway. We screened for mutations in RELN or VLDLR and compared the phenotype of these patients with that of previously reported patients. All patients had profound cerebellar hypoplasia on MRI with peculiar cerebellar morphology, associated with flattened pons and neocortical abnormalities. Patient 1 had profound motor and intellectual disability with moderate lissencephaly suggestive of RELN mutations and was shown to harbor a splicing homozygous RELN mutation. The four other patients had a milder phenotype consistent with CARMQ1 (cerebellar ataxia and mental retardation with or without quadrupedal locomotion). These patients showed mild simplification or thickening of cortical gyration and had VLDLR mutations. Reelin signaling regulates neuronal migration in the developing mammalian brain. VLDLR is a key component of the Reelin pathway. Our patients had a very small and dysplatic cerebellar vermis that should suggest the involvement of these genes. Moreover, differences in clinical severity, involvement of the cerebellar hemispheres, together with the severity of the neocortical defect, enables RELN-mutated patients to be distinguished from VLDLR-mutated patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Rasmussen's encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug-resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF-α) in RE pathophysiology., Methods: We report an open-label study evaluating the efficacy and the safety of anti-TNF-α therapy (adalimumab) in 11 patients with RE. The primary outcome criterion was the decrease of seizure frequency. The secondary outcome criteria were neurologic and cognitive outcomes and existence of side effects., Results: Adalimumab was introduced with a median delay of 31 months after seizure onset (range 1 month to 16 years), and follow-up was for a median period of 18 months (range 9-54 months). There was a significant seizure frequency decrease after adalimumab administration (from a median of 360 to a median of 32 seizures per quarter, p ≤ 0.01). Statistical analysis showed that adalimumab had a significant intrinsic effect (p < 0.005) independent from disease fluctuations. Five patients (45%) were found to have sustained improvement over consecutive quarters in seizure frequency (decrease of 50%) on adalimumab. Three of these five patients also had no further neurocognitive deterioration. Adalimumab was well tolerated., Significance: Our study reports efficacy of adalimumab in terms of seizure frequency control. In addition, stabilization of functional decline occurred in three patients. This efficacy might be particularly relevant for atypical slowly progressive forms of RE, in which hemispherotomy is not clearly indicated. Due to our study limitations, further studies are mandatory to confirm these preliminary results., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objectives: To describe the clinical profile and the prevalence of severe congenital neutropenia (SCN) and HAX1 mutations, so-called Kostmann syndrome, in France., Study Design: Two pedigrees were identified from the French registry., Results: The study included five subjects (three males), which represent 0.7% of the 759 SCN cases registered in France. The age at diagnosis was 0.3 years (range: 0.1-1.2 years) and the median age at the last follow-up was 7.3 years (range: 1.2-17.8 years). A novel large homozygous deletion of the HAX1 gene (exons 2-5) was found in one pedigree; while, a homozygous frameshift mutation was identified in exon 3 (c.430dupG, p.Val144fs) in the second pedigree. Severe bacterial infections were observed in four patients, including two cases of sepsis, one case of pancolitis, a lung abscess, and recurrent cellulitis and stomatitis. During routine follow-up, the median neutrophil value was 0.16 × 10(9)/L, associated with monocytosis (2 × 10(9)/L). Bone marrow (BM) smears revealed a decrease of the granulocytic lineage with no mature myeloid cells above the myelocytes. One patient died at age 2 from neurological complications, while two other patients, including one who underwent a hematopoietic stem cell transplantation (HSCT) at age 5, are living with very severe neurological retardation., Conclusions: SCN with HAX1 mutations, is a rare sub type of congenital neutropenia, mostly observed in population from Sweden and Asia minor, associating frequently neurological retardation, when the mutations involved the B isoform of the protein., (© 2014 Wiley Periodicals, Inc.)

Purpose: To determine what epilepsy types occur after herpetic encephalitis and what are the determinant factors for subsequent infantile spasms., Methods: We analyzed retrospectively the clinical history of 22 patients, referred to Necker and Saint Vincent de Paul Hospitals (Paris) through the French pediatric epilepsy network from March 1986 to April 2010 and who developed epilepsy some months after herpetic encephalitis. We focused on seizure semiology with video-electroencephalography (EEG) recording, and on neuroradiology and epilepsy follow-up., Key Findings: Fourteen patients developed pharmacoresistant spasms, and eight developed focal epilepsy, but none had both. The patients who developed spasms were more frequently younger than 30 months at age of onset of epilepsy and had herpetic encephalitis earlier (mean 10.6 months of age) than those who developed focal epilepsy (mean 59.7 and 39.6 months, respectively). Epilepsy follow-up was similar in both groups (8.5 and 11 years, respectively). We found 26 affected cerebral areas; none alone was related to the development of epileptic spasms., Significance: Risk factors to develop epileptic spasms were to have had herpetic encephalitis early (mean 10 months); to be significantly younger at onset of epilepsy (mean 22.1 months); and to have cerebral lesions involving the insula, the hippocampus, and the temporal pole., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Background: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found in about 10% of EOEE patients. Our objective was to confirm that KCNQ2 was an important gene to include in the diagnosis workup of EOEEs and to fully describe the clinical and EEG features of mutated patients., Methods: We have screened KCNQ2 in a cohort of 71 patients with an EOEE, without any brain structural abnormality. To be included in the cohort, patient's epilepsy should begin before three months of age and be associated with abnormal interictal EEG and neurological impairment. Brain MRI should not show any structural abnormality that could account for the epilepsy., Results: Out of those 71 patients, 16 had a de novo mutation in KCNQ2 (23%). Interestingly, in the majority of the cases, the initial epileptic features of these patients were comparable to those previously described in the case of benign familial neonatal epilepsy (BFNE) also caused by KCNQ2 mutations. However, in contrast to BFNE, the interictal background EEG was altered and displayed multifocal spikes or a suppression-burst pattern. The ongoing epilepsy and development were highly variable but overall severe: 15/16 had obvious cognitive impairment, half of the patients became seizure-free, 5/16 could walk before the age of 3 and only 2/16 patient acquired the ability to speak., Conclusion: This study confirms that KCNQ2 is frequently mutated de novo in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the neurological and epileptic evolution is variable.

Dyslexia is a frequent neurodevelopmental learning disorder. To date, nine susceptibility loci have been identified, one of them being DYX9, located in Xq27. We performed the first French SNP linkage study followed by candidate gene investigation in dyslexia by studying 12 multiplex families (58 subjects) with at least two children affected, according to categorical restrictive criteria for phenotype definition. Significant results emerged on Xq27.3 within DYX9. The maximum multipoint LOD score reached 3,884 between rs12558359 and rs454992. Within this region, seven candidate genes were investigated for mutations in exonic sequences (CXORF1, CXORF51, SLITRK2, FMR1, FMR2, ASFMR1, FMR1NB), all having a role during brain development. We further looked for 5'UTR trinucleotide repeats in FMR1 and FMR2 genes. No mutation or polymorphism co-segregating with dyslexia was found. This finding in French families with Dyslexia showed significant linkage on Xq27.3 enclosing FRAXA, and consequently confirmed the DYX9 region as a robust susceptibility locus. We reduced the previously described interval from 6.8 (DXS1227-DXS8091) to 4 Mb also disclosing a higher LOD score.

Orofaciodigital syndromes (OFDSs) consist of a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of 13 OFDS subtypes. Here, by a combined approach of homozygozity mapping and exome ciliary sequencing, we identified truncating TCTN3 mutations as the cause of an extreme form of OFD associated with bone dysplasia, tibial defect, cystic kidneys, and brain anomalies (OFD IV, Mohr-Majewski syndrome). Analysis of 184 individuals with various ciliopathies (OFD, Meckel, Joubert, and short rib polydactyly syndromes) led us to identify four additional truncating TCTN3 mutations in unrelated fetal cases with overlapping Meckel and OFD IV syndromes and one homozygous missense mutation in a family with Joubert syndrome. By exploring roles of TCTN3 in human ciliary related functions, we found that TCTN3 is necessary for transduction of the sonic hedgehog (SHH) signaling pathway, as revealed by abnormal processing of GLI3 in patient cells. These results are consistent with the suggested role of its murine ortholog, which forms a complex at the ciliary transition zone with TCTN1 and TCTN2, both of which are also implicated in the transduction of SHH signaling. Overall, our data show the involvement of the transition zone protein TCTN3 in the regulation of the key SHH signaling pathway and that its disruption causes a severe form of ciliopathy, combining features of Meckel and OFD IV syndromes., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Purpose: STXBP1 (MUNC18-1) mutations have been associated with various types of epilepsies, mostly beginning early in life. To refine the phenotype associated with STXBP1 aberrations in early onset epileptic syndromes, we studied this gene in a cohort of patients with early onset epileptic encephalopathy., Methods: STXBP1 was screened in a multicenter cohort of 52 patients with early onset epilepsy (first seizure observed before the age of 3 months), no cortical malformation on brain magnetic resonance imaging (MRI), and negative metabolic screening. Three groups of patients could be distinguished in this cohort: (1) Ohtahara syndromes (n = 38); (2) early myoclonic encephalopathies (n = 7); and (3) early onset epileptic encephalopathies that did not match any familiar syndrome (n = 7). None of the patients displayed any cortical malformation on brain MRI and all were screened through multiple video-electroencephalography (EEG) recordings for a time period spanning from birth to their sixth postnatal month. Subsequently, patients had standard EEG or video-EEG recordings., Key Findings: We found five novel STXBP1 mutations in patients for whom video-EEG recordings could be sampled from the beginning of the disease. All patients with a mutation displayed Ohtahara syndrome, since most early seizures could be classified as epileptic spasms and since the silent EEG periods were on average shorter than bursts. However, each patient in addition displayed a particular clinical and EEG feature: In two patients, early seizures were clonic, with very early EEG studies exhibiting relatively low amplitude bursts of activity before progressing into a typical suppression-burst pattern, whereas the three other patients displayed epileptic spasms associated with typical suppression-burst patterns starting from the early recordings. Epilepsy dramatically improved after 6 months and finally disappeared before the end of the first year of life for four patients; the remaining one patient had few seizures until 18 months of age. In parallel, EEG paroxysmal abnormalities disappeared in three patients and decreased in two, giving place to continuous activity with fast rhythms. Each patient displayed frequent nonepileptic movement disorders that could easily be mistaken for epileptic seizures. These movements could be observed as early as the neonatal period and, unlike seizures, persisted during all the follow-up period., Significance: We confirm that STXBP1 is a major gene to screen in cases of Ohtahara syndrome, since it is mutated in >10% of the Ohtahara patients within our cohort. This gene should particularly be tested in the case of a surprising evolution of the patient condition if epileptic seizures and EEG paroxysmal activity disappear and are replaced by fast rhythms after the end of the first postnatal year., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Myoclonus dystonia (M-D) is a rare genetic movement disorder characterized by a combination of myoclonic jerks and dystonia. It is usually due to mutations in the SGCE gene. We report on a patient with a typical M-D syndrome, but also short stature, microcephaly, and mental retardation. Molecular analysis showed no mutations within the SGCE gene but a microdeletion encompassing the SGCE gene in chromosome region 7q21. Array-CGH analysis showed that the deletion spanned approximately 1.88 Mb. We suggest that M-D plus patients with mental retardation, microcephaly, dysmorphism, or short stature, all frequently associated disorders, should be screened for 7q21 microdeletion. By examining previously published cases of mental retardation associated with pure 7q21 deletions, we identified two distinct regions of respectively 455 and 496 kb that are critical for mental retardation and growth retardation. Among the genes located within these regions, LOC253012, also known as HEPACAM2, is a good candidate for both mental retardation and microcephaly., (Copyright 2010 Wiley-Liss, Inc.)

Introduction: Dyslexia is a complex neurodevelopemental disorder that affects 5 to 10% of school-age children. This condition consists in a specific learning disability with a neurological origin. These learning difficulties are unexpected in relation to other cognitive abilities and the provision of efficient classroom instruction. A range of neurobiological investigations suggests that disruption of the parieto-temporo-occipital systems underlies a failure of skilled reading to develop. The observation that dyslexia is both a familial and heritable problem was made early on and was confirmed by twin studies. They also suggested that both genetic and environmental factors are involved. Several loci have been implicated in dyslexia, notably on chromosomes 2, 3, 6, 15 and 18 and some candidate genes have been proposed, but no functional mutation has yet been identified., Literature Review: Dyslexia seldom appears isolated and dyslexic people are very likely to present other kinds of learning disabilities or psychiatric disorders. Specific language impairment, often with a mild outcome, is the most frequently associated with dyslexia. Indeed, late language development is often reported by dyslexic patients and also occurs more frequently among their siblings. Genetic linkage studies suggest some common genetic factor underlying this comorbidity. Dyscalculia is associated with dyslexia in 25% of cases, but most people with dyscalculia do not have any sign of dyslexia. The question of whether dyscalculia associated with dyslexia and dyscalculia itself rely on the same cognitive impairment is still controversial. Impaired motor development is also a common feature that affects nearly 50% of dyslexics and dyslexia is frequent among dyspraxic patients. This association raises the discussion on the role of motor impairment in dyslexia's physiopathology and the cerebellar theory of dyslexia. Beyond its link with other learning disorders, the study of dyslexia's comorbidity highlights psychopathological issues. ADHD is the most frequent psychiatric disorder associated with dyslexia. Underpinnings of this link between the two disorders seem to rely on common cognitive and genetic factors. Some authors have proposed a candidate gene ADRA2A to determine the condition including ADHD and dyslexia. In addition, dyslexics are exposed to a higher risk of anxiodepressive and behavioural disorders. Dyslexic children experience three times more behavioural disorders and one third of children with behavioural problems turn out to be affected by dyslexia. The literature study reveals inconsistent findings about depressed mood among dyslexics, but evidence of a persistent increase in the rate of anxiety disorders. The authors put forward the impact of environmental factors to explain these psychiatric comorbidities., Conclusion: This review emphasizes dyslexia's comorbidities because they represent an important issue, both from a scientific and clinical point of view. Indeed, for clinicians, children showing multiple learning disabilities have specific reeducation and educational needs and dyslexics have a higher risk of emotional and behavioural disorders. On the other hand, dyslexia's comorbidity study provides a powerful method for researchers to investigate the still unknown physiopathology of dyslexia., (2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Objective: With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype., Design: Retrospective study. Subjects A total of 63 patients with posteriorly predominant lissencephaly., Interventions: Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined., Results: Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly., Conclusion: Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.

Introduction: Developmental dyslexia (DD) is a frequent language-based learning disorder. The predominant etiological view postulates that reading problems originate from a phonological impairment., Method: We studied mismatch negativity (MMN) and Late Discriminative Negativity (LDN) to syllables change in both children (n=12; 8-12 years) and young adults (n=15; 14-23 years) with DD compared with controls., Results/discussion: The present study confirmed abnormal automatic discrimination of syllable changes in both children and adults with developmental dyslexia. MMN topographic, amplitude and latency group differences were evidenced, suggesting different brain mechanisms involved in elementary auditory stimulus change-detection in DD, especially in the left hemisphere. The LDN results demonstrated that the auditory disorder of temporal processing in DD children becomes more serious at late stages of information processing and that the apparent cerebral hypo reactivity to speech changes in DD actually may correspond to additional processes. The age-related differences observed in both MMN and LDN topographies, amplitudes and latency between subjects with DD and controls could indicate different developmental courses in the neural representation of basic speech sounds in good and poor readers, with a tendency to normalization with increasing age., Conclusion: Our results showing atypical electrophysiological concomitants of speech auditory perception in DD strongly support the hypothesis of deviant cortical organization in DD.

Learning disabilities represent the main childhood complication in neurofibromatosis type 1 (NF1). Patients frequently exhibit T2-weighted hyperintensities called unidentified bright objects (UBOs) on brain magnetic resonance imaging (MRI), with unclear relationship to such cognitive disabilities. This study aimed to determine whether thalamo-striatal UBOs correlate with cognitive disturbances. Thirty-seven NF1 children were studied: 24 with UBOs (18 of which were thalamo-striatal UBOs), and 13 without UBOs. NF1 subjects carrying thalamo-striatal UBOs had significantly lower IQs and visuospatial performances than those without UBOs in this location. These results suggest that UBOs may contribute to NF1 cognitive impairments through thalamo-cortical dysfunction.

Pompe disease is an autosomal recessive glycogen storage disorder caused by acid-alpha-glucosidase deficiency. The infantile form is usually fatal by 1 year of age in the absence of specific therapy. We report the cardiac follow-up of a 4-month-old boy treated with enzyme replacement therapy (ERT) for 8 months. The patient had no cardiac failure at the age of 1 year. Before starting ERT, ECG showed a shortened PR interval, with huge QRS complexes and biventricular hypertrophy; echocardiography demonstrated major hypertrophic cardiomyopathy. The QRS voltage (SV1+RV6) decreased from 13 to 2.9 mV after 32 weeks of ERT, suggesting a progressive reduction of cardiac hypertrophy and intracellular glycogen excess. The PR interval increased from 60 to 90 ms. A block of the right bundle branch appeared after 13 weeks of treatment. The indexed left ventricular mass decreased from 240 to 90 g/m2 after 30 weeks of ERT. The left ventricular ejection fraction decreased transitorily between the 5th and the 15 th weeks of treatment. In summary, ERT is an efficient therapeutic approach for the cardiomyopathy of infantile Pompe disease. However, the possible occurrence of a right bundle branch block and a transitory alteration in the ejection fraction highlight the importance of cardiac follow-up.

Background: Continuous spike-waves during slow sleep syndrome (CSWSS) is a rare epileptic syndrome occurring in children, which is characterized by the association of epilepsy, neuropsychological disorders, and abnormal paroxysmal electroencephalographic (EEG) discharges activated by sleep. Language can be affected but, to date, language disorders and their long-term outcome have been documented only rarely., Purposes: Description of language impairment in patients with the CSWSS., Methods: We performed a detailed language testing in 10 right-handed children and adolescents with the CSWSS. Their pragmatic performance was compared to that of a control population of 36 children aged 6-10 years., Results: Patients with CSWSS had lower scores in tests measuring their lexical, morphosyntactic, and pragmatic skills compared to controls. Comprehension remains unaffected. In addition, language impairment was found to be just as severe in patients in remission as those still in an active phase., Conclusions: We found severe language impairments in lexical and syntactic skills. The language profile is different from that observed in the Landau-Kleffner syndrome. Moreover patients in remission and those in an active phase of the CSWSS have the same language impairment profiles. This confirms the poor long-term neuropsychological prognosis. Our results raise points about the relationship between epileptic activity and language development. This pilot study underscores the need to assess language, and especially pragmatic skills, and to study long-term outcome in such childhood epileptic syndromes.

We report the case of a young girl who presented severe learning disabilities in oral and written language related to a continuous spike-waves during slow sleep (CSWS) syndrome. A sleep EEG recording obtained in her younger brother, who presented a clinical pattern suggesting developmental dysphasia, also showed a CSWS syndrome. These two clinical cases underscore the need to look for this syndrome in the siblings of an affected child when learning difficulties appear in a child who previously had normal psychomotor development.

Unlabelled: Neurofibromatosis 1 (NF1) is a frequent genetic disease. Diagnostic criterias were established in 1988. The patients can exhibit various and unpredictable complications., Objectives: To check the efficiency of a coordinated follow-up in specialized multidisciplinary centers providing a higher quality of management and to have a better knowledge of the complications including their true frequencies., Population and Methods: We report a serie of 100 NF1 children who were followed-up during 4 years in a specialized center at the Tours University Hospital. Three hospital check-up at 2-5, 6-7, 14-15 years of age were performed as well as an annual physical examination., Results: In our serie, the mean age was 7.8 years old with a sex ratio of 1. The mean age at diagnosis was 3.8 years old and the main diagnosis criteria were the café-au-lait spots and the family history for 80% of the patients. The optic nerve glioma has a low frequency of 5%. Learning disabilities clearly represent the most frequent complication (46% of the patients)., Conclusion: An early detection of these difficulties is a priority for the appropriate management of these children.

Unlabelled: Methylphenidate (MPH) is a potential therapeutic tool for Attention Deficit with Hyperactivity Disorders (ADHD). In addition to the immediate-release formulation, Ritalin, two extended-release formulations, Ritalin LA and Concerta are available and allow a once-daily administration. We compared the respective benefits of both formulations for the patients and their family in terms of efficacy, handling and tolerance., Patients and Methods: This prospective study was based on 30 children aged 6 to 15 years. All patients had a confirmed ADHD and were efficiently treated with Ritalin. The children were consecutively treated with Ritalin LA and Concerta, with a comparable MPH daily dosage, during 2 months for each molecule. The 3 drugs were evaluated individually and comparatively through a battery of questionnaires submitted to the parents and the teachers of each child., Results: Extended-release MPH efficacy was comparable to the immediate-release formulation, Ritalin. For both of them, the once-daily administration appeared beneficial. Concerta was finally prescribed in 18 children, Ritalin LA in 8 cases and Ritalin in 4 cases. In each case the medical choice was consistent with the parents preference. Concerta was appreciated for its persisting efficacy in late afternoon during homework. Concerta and Ritalin LA did not induce significant adverse effects, especially regarding alimentation and sleep., Conclusions: MPH therapy in ADHD carries an excellent risk/benefit ratio without addictive induced behaviours. The extended-release MPH formulations provide an improvement for the patients in keeping with Ritalin efficacy through a once-daily administration. Regardless of its formulation, MPH indications and guidelines must be respected.

Benign childhood epilepsy with centrotemporal spikes (BECTS) is regarded as a benign form of epilepsy because of its usually favorable outcome, in terms of seizures. Eighteen children with BECTS were studied in terms of neuropsychological and learning abilities: intellectual quotient, oral language (phonological production, naming skills, verbal fluency and syntactic comprehension), drawing and visuo-spatial skills, visual and selective attention, verbal and visuo-spatial memory, reading, numeracy and spelling. The mean IQ of the population was within the normal range, but individual results were heterogeneous. Verbal functions and memory were normal. In contrast, drawing and visuo-spatial skills, attention and visuo-spatial memory were significantly weak compared to the normal range for age. Reading, numeracy and/or spelling ability were significantly delayed by one academic year or more in ten of the children. In conclusion, despite its benign outcome in terms of epilepsy, BECTS can be accompanied by specific cognitive disorders and low academic achievement.

Unlabelled: Introduction. Neurogenic Thoracic Outlet Syndrome (NTOS) is a chronic lower trunk brachial plexus entrapment caused by a cervical rib or a fibrous band. True NTOS is rare and progresses usually slowly. Case report. A 12-year-old girl complained of numbness and weakness of the right upper limb immediately after an orthopedic surgical procedure for scoliosis. Neurological and neurophysiological features were both consistent with a neurogenic thoracic outlet syndrome (NTOS)., Conclusion: This observation illustrates the risk of NTOS after certain surgical procedures, especially when a prolonged prone position with abducted shoulders is required.

Ischemic strokes represent a rare condition in childhood, mostly revealed by a motor deficit. In the pediatric age, strokes are different than in adulthood where atherosclerosis is the major cause. The etiologies of stroke in childhood are rather multiple and each of them is rare. In nearly half of the pediatric cases no cause can be found and usually no recurrence occurs. The aim of this presentation is to propose a diagnosis strategy for ischemic strokes in children. An extensive search should be performed in every children presenting a stroke episode even if the initial outcome appears favorable. Such investigations could improve our understanding and therapeutic strategies of stroke in childhood, a condition where the cognitive and functional prognosis can be severely compromised.

Although Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) has a good prognosis, a few studies have suggested the existence of language disorders relating to the interictal dysfunction of perisylvian language areas. In this study, we focused on language assessment in 16 children aged 6-15 currently affected by BECTS or in remission. An important proportion of children showed moderate or more severe language impairment. The most affected domains were expressive grammar and literacy skills. We found linguistic deficits during the course of epilepsy but also persistent deficits in children in remission, suggesting possible long-term effects. Our results support the hypothesis that BECTS may be associated with impairment to language and suggest the possibility of a direct link between epileptic activity and language development, and the existence of long-term consequences.

Background: Degenerative-like neuro-Langerhans cell histiocytosis (DN-LCH) is a rare complication of LCH marked by progressive cerebellar ataxia. No treatment has so far been shown to slow this progression., Procedure: All-trans retinoic acid (ATRA) was administered orally at a dose of 45 mg/m(2) daily for 6 weeks and then 2 weeks every month for 1 year. The endpoints were clinical status at 1 year (assessed with rating scales for ataxia and disability), adverse effects, and changes in neurological abnormalities on MRI., Results: Ten patients were studied. The treatment was well tolerated. All the patients were clinically stable at the end of the study. No MRI changes were noted., Conclusions: DN-LCH appeared to be stable during ATRA therapy, but further studies are required to appreciate the possible long-term benefits of ATRA., (Copyright 2004 Wiley-Liss, Inc.)

Objective: To document the frequency and outcome of endocrine involvement in pediatric-onset Langerhans' cell histiocytosis (LCH), and the association with other types of organ involvement., Study Design: This retrospective nationwide multicenter study involved 589 patients with pediatric-onset LCH, 148 of whom had endocrine dysfunction. Median follow-up was 11.6 years., Results: Pituitary dysfunction was present in 145 patients, and 141 had diabetes insipidus (DI). The estimated 10-year risks of pituitary involvement were 24.2% +/- 1.8%. GH deficiency occurred in 61 patients. Median age at onset was 2.8 years for LCH, 3.9 years for DI, and 7.7 years for GH deficiency. The risk of cranial involvement; ear, nose, and throat involvement; pneumothorax; and cholangitis was significantly higher in patients with endocrinopathy. The chronology of episodes did not support a causal link between pituitary involvement and involvement of other organs. Systemic treatment of LCH did not prevent pituitary involvement. The most severe complication was a neurodegenerative syndrome, which affected 4.3% and 10.8% of patients, respectively, 5 and 15 years after initial diagnosis, and appeared to be linked to pituitary involvement., Conclusion: Patients who develop endocrine LCH disorders are at a high risk of neurodegenerative LCH and require long-term follow-up.

Purpose: The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike-waves during slow sleep (CSWS) and Landau-Kleffner syndromes, which are two rare epileptic syndromes occurring in children., Methods: We enrolled seven young adults, five who had a CSWS syndrome, and two, a Landau-Kleffner syndrome in childhood. We evaluated their intellectual level as well as their oral and written language and executive functions., Results: This study confirmed that the epilepsy associated with these syndromes has a good prognosis. Only one patient still had active epilepsy. However, the neuropsychological disorders particular to each syndrome persisted. Only two patients had followed a normal pathway in school. Three of the five patients with a CSWS syndrome during childhood remained globally and nonselectively mentally deficient. We found no evidence of the persistence of a dysexecutive syndrome in this study group. The intellectual functions of the two patients with Landau-Kleffner syndrome were normal; however, their everyday lives were disrupted by severe, disabling language disturbances. We discuss the role of some prognostic factors such as the location of the interictal electric focus and the age at onset of CSWS., Conclusions: These two epileptic syndromes of childhood are very similar in many respects, but their clinical outcomes in adulthood are different.

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys. Based on the observations of 3 new cases, we confirm the phenotype in affected boys, describe additional MRI findings, report the neuropathological data, and show that carrier females may exhibit neurological and magnetic resonance imaging abnormalities. In affected boys, consistent clinical features of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia are intractable epilepsy of neonatal onset, severe hypotonia, poor responsiveness, genital abnormalities, and early death. On magnetic resonance imaging, a gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia and complete agenesis of the corpus callosum are consistently found. Neuropathological examination of the brain shows a trilayered cortex containing exclusively pyramidal neurons, a neuronal migration defect, a disorganization of the basal ganglia, and gliotic and spongy white matter. Finally, females related to affected boys may have mental retardation and epilepsy, and they often display agenesis of the corpus callosum. These findings expand the phenotype of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia, may help in the detection of carrier females in affected families, and give arguments for a semidominant X-linked mode of inheritance.

We report a longitudinal, electroencephalographic and neuropsychological analysis of epilepsy with continuous spikes and waves during slow sleep (CSWS) in a 19 year-old boy. The clinical course fluctuated, with temporary worsening or improvement of the paroxysmal abnormalities, epilepsy and cognitive functions. At the end of the follow-up period, seizures persisted. Evaluation of the boy's behaviour, language and cognitive function suggested a dysexecutive syndrome. We discuss the relationship between paroxysmal abnormalities and neuropsychological disorders.

This retrospective study detailed clinical and radiologic involvement of the central nervous system related to Langerhans cell histiocytosis in 18 French children. We excluded cases of isolated hypothalamic-pituitary dysfunction or spinal involvement. Cerebellar symptoms were the most common clinical symptoms. Two different patterns of magnetic resonance or computed tomographic images were identified: demyelination and gliosis or atrophy, described as degenerative lesions, mostly located in the cerebellum in 10 children, or tumor-like lesions occurring in any part of the brain in 13 children. Six children had both types of lesion. The clinical cerebellar syndrome correlated with the specific imaging pattern suggestive of a cerebellar degenerative lesion, which did not show any changes after treatment. As suggested by this study and previous clinical and histologic reports, it is believed that brain involvement in the course of Langerhans cell histiocytosis might arise from different disease mechanisms: primary histiocyte proliferation and secondary atrophy or demyelination and gliosis of unknown origin. Treatment consequently should be adapted to the supposed mechanism of the lesion.

The major aim of this study was to assess whether the syndrome of nonverbal learning disabilities described in hydrocephalic children is observed in adulthood. Eleven adults shunted for congenital hydrocephalus related to spina bifida and eight adults shunted for hydrocephalus related to aqueductal stenosis were administered an extensive neuropsychologic battery to investigate discrepancies between verbal and visuospatial cognition, verbal and visuospatial long-term memory, and psycho-social adaptive abilities. The results showed no discrepancies between Wechsler Performance IQ or Verbal IQ in either hydrocephalic group. Nevertheless, the subjects with spina bifida appeared more cognitively impaired than the subjects with aqueductal stenosis, who performed normally on the Wechsler Adult Intelligence Scale-Revised. Memory assessment using Signoret's Memory Battery revealed no discrepancy between verbal and visuospatial memory in the hydrocephalic group. Nevertheless, the subjects with spina bifida had poorer verbal and visuospatial memory performance than the subjects with aqueductal stenosis. There were no differences on the Vineland Adaptive Behavioral Scale between subjects with spina bifida and those with aqueductal stenosis in autonomy, socialization, and daily living skills. These results suggest that shunted congenital hydrocephalus is not characterized by nonverbal learning disabilities syndrome in adolescence or in adulthood.

Familial hemiplegic migraine (HM) is an autosomal dominant migraine with aura. In 20% of HM families, HM is associated with a mild permanent cerebellar ataxia (PCA). The CACNA1A gene encoding the alpha1A subunit of P/Q-type voltage-gated calcium channels is involved in 50% of unselected HM families and in all families with HM/PCA. Four CACNA1A missense mutations have been identified in HM: two in pure HM and two in HM/PCA. Different CACNA1A mutations have been identified in other autosomal dominant conditions: mutations leading to a truncated protein in episodic ataxia type 2 (EA2), small expansions of a CAG trinucleotide in spinocerebellar ataxia type 6 and also in three families with EA2 features, and, finally, a missense mutation in a single family suffering from episodic ataxia and severe progressive PCA. We screened 16 families and 3 nonfamilial case patients affected by HM/PCA for specific CACNA1A mutations and found nine families and one nonfamilial case with the same T666M mutation, one new mutation (D715E) in one family, and no CAG repeat expansion. Both T666M and D715E substitutions were absent in 12 probands belonging to pure HM families whose disease appears to be linked to CACNA1A. Finally, haplotyping with neighboring markers suggested that T666M arose through recurrent mutational events. These data could indicate that the PCA observed in 20% of HM families results from specific pathophysiologic mechanisms.

Report of a case and review of the literature: We report the case of a seven-year-old female kabuki patient suffering from severe bilateral deafness related to Mondini dysplasia and ossicular anomalies. A review of the literature in English confirms that hearing loss is a major component of Kabuki Syndrome (KS) with a frequency at around 32%. However the possible mechanisms have not been fully described and hearing loss is often attributed to otitis media, but one reported case had severe ossicular malformations, two had sensorineural deafness and three others had mixed deafness. Our observation is the first reported case of Mondini dysplasia in KS. Awareness by physicians of this problem has a major practical consequence as diagnosis of Mondini dysplasia implies searching for and surgical prevention and treatment of perilymphatic fistula in order to prevent meningitis.

Hemisphere specialization for language was studied in 10 children with expressive developmental dysphasia (DD) (mean age 10 years 4 months) submitted to a dichotic listening task (in a word free-recall task and forced-attention task) and a finger tapping/vocalization dual-task paradigm. A nonsense shape dichaptic task was also introduced to control right hemispheric processing. Performances of dysphasic children were compared to those obtained from 15 normal children. The results showed that controls had a right ear advantage in free-recall (words) dichotic listening task and a significant right ear advantage in forced-right-attention task, with a change in ear asymmetry as a consequence of instruction. In the dysphasic group we observed a significant right ear advantage in the free-recall dichotic listening task and no change in ear asymmetry during forced right or forced left condition. Results in time sharing paradigm and nonsense dichaptic task are more difficult to interpret, because there was no interaction between group and condition. These results cannot support a complete left hemisphere dysfunction in developmental dysphasia.