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Miladi L.,Necker Enfants Malades Hospital | Journe A.,Necker Enfants Malades Hospital | Mousny M.,Cliniques Universitaires Saint Luc
European Spine Journal | Year: 2013

Purpose The purpose of this study was to review the preliminary results of an original fusionless method of treatment for progressive scoliosis in young children. Methods This study retrospectively reviewed the clinical records and radiographs of 23 children with progressive scoliosis who failed to respond to conservative treatment and underwent fusionless surgery using a single solid growing rod construct. All of them were ambulatory and had a followup of minimum 2 years. Sixteen patients were treated by consecutive distraction of a single intramuscular rod, and seven patients with rodding and anterior apical convex fusion. The etiology of the scoliosis included 11 idiopathic, 6 syndromic, 4 congenital, and 2 neurofibromatosis. At initial surgery, the average age was 9.3 ± 2.8 years, with a mean Cobb angle of 68° ± 32°. Six patients underwent progressive scoliosis correction in a Stagnara cast prior to surgery, and one patient with an external halo-pelvic Ilizarov device. Results Fusionless single rodding allowed to maintain scoliosis correction in all patients. At an average of 3.5 ± 0.9 years after initial surgery, the 23 patients showed a correction of 57 % in the magnitude of the original curvature. Trunk height increase was documented in all patients and ranged from 1.5 to 11.9 cm. Rod failure was found in three patients and two patients had hardware infection. Only four cases of proximal junctional kyphosis were found at last follow-up. Conclusions Preliminary results from these series of patients show that the presented fusionless single growing rod technique allows to maintain correction of progressive early onset scoliosis while permitting spinal growth, with low complication rate. With this technique, lengthening procedures are used only once in every 10 months and patients are more comfortable as no brace is needed in most cases. This technique does not require any specific spine device. The procedure is simple and efficacious as long as some guidelines are respected. © Springer-Verlag 2012.


Valayannopoulos V.,Necker Enfants Malades Hospital | Nicely H.,BioMarin Pharmaceutical | Harmatz P.,Childrens Hospital Oakland Research Institute | Turbeville S.,BioMarin Pharmaceutical
Orphanet Journal of Rare Diseases | Year: 2010

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B leading to the accumulation of dermatan sulfate. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (generally >100 μg/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 μg/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS VI, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. Diagnosis generally requires evidence of clinical phenotype, arylsulfatase B enzyme activity <10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS I, II IVA, VII), sialidosis and mucolipidosis. Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme®), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided. © 2010 Valayannopoulos et al; licensee BioMed Central Ltd.


Nabbout R.,Necker Enfants Malades Hospital
Epilepsia | Year: 2012

Summary The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies. © 2012 International League Against Epilepsy.


Valayannopoulos V.,Necker Enfants Malades Hospital | Wijburg F.A.,University of Amsterdam
Rheumatology | Year: 2011

Better understanding of disease pathophysiology, improved supportive care and availability of diseasespecific treatments for some of the mucopolysaccharidosis (MPS) disorders have greatly improved the outlook for patients with MPS disorders. Optimal management of these multisystemic disorders involves a multidisciplinary team and regular, comprehensive follow-up. Enzyme replacement therapy (ERT) is now available for MPS I (Hurler, Hurler-Scheie and Scheie syndromes) (laronidase), MPS II (Hunter syndrome) (idursulfase) and MPS VI Maroteaux-Lamy (galsulfase), and is in development for MPS IV (Morquio syndrome) and MPS VII (Sly syndrome). Benefits of ERT can include improved walking ability, improved respiration and enhanced quality of life. Haematopoietic stem cell transplantation (HSCT) can preserve cognition and prolong survival in very young children with the most severe form of MPS I, and is under investigation for several other MPS disorders. Better tissue matching techniques, improved graft-vs-host prophylaxis and more targeted conditioning regimens have improved morbidity and mortality associated with HSCT. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.


Introduction: First-trimester Down syndrome (DS) screening combining maternal age, serum markers (pregnancy-associated plasma protein-A and beta-human chorionic gonadotropin) and nuchal translucency (NT) gives an 85% detection rate for a 5% false-positive rate. These results largely depend on quality assessment of biochemical markers and of NT. In routine practice, despite an ultrasound quality control organization, NT images can be considered inadequate. The aim of the study was to evaluate the consequences for risk calculation when NT measurement is not taken into account. Material and Method: Comparison of detection and false-positive rates of first-trimester DS screening (PerkinElmer, Turku, Finland), with and without NT, based on a retrospective study of 117,126 patients including 274 trisomy 21-affected fetuses. NT was measured by more than 3,000 certified sonographers. Results: There was no significant difference in detection rates between the two strategies including or excluding NT measurement (86.7 vs. 81.8%). However, there was a significant difference in the false-positive rates (2.23 vs. 9.97%, p < 0.001). Discussion: Sonographers should be aware that removing NT from combined first-trimester screening would result in a 5-fold increase in false-positive rate to maintain the expected detection rates. This should be an incentive for maintaining quality in NT measurement. © 2015 S. Karger AG, Basel Copyright © 2015, S. Karger AG. All rights reserved.


Bojan M.,Necker Enfants Malades Hospital | Gioanni S.,Necker Enfants Malades Hospital | Vouhe P.R.,Necker Enfants Malades Hospital | Vouhe P.R.,University of Paris Descartes | And 2 more authors.
Kidney International | Year: 2012

Association between early renal replacement therapy and better survival has been reported in adults with postoperative kidney injury, but not in children undergoing cardiac surgery. We conducted a retrospective cohort study of 146 neonates and infants requiring peritoneal dialysis following cardiac surgery in a tertiary referral hospital. A propensity score was used to limit selection bias due to timing of dialysis, and included baseline and intraoperative characteristics, requirement for postoperative extracorporeal membrane oxygenation, and creatinine clearance variation. Inverse probability of treatment weighting resulted in good balance between groups for all baseline and intraoperative variables. After weighting, 30-day and 90-day mortality were compared between the 109 patients placed on dialysis early, within the first day of surgery, and those with delayed dialysis, commencing on the second day of surgery or later, using logistic regression and survival analysis. Mortality was 28.1% at 30 days, and was 36.3% during follow-up. Early dialysis was associated with a 46.7% decrease in the 30-day and a 43.5% decrease in the 90-day mortality rate when compared with delayed dialysis. All other short-term outcome variables were similar. Thus, initiation of peritoneal dialysis on the day of or the first day following surgery was associated with a significant decrease in mortality in neonates and infants with acute kidney injury. © 2012 International Society of Nephrology.


Bojan M.,Necker Enfants Malades Hospital | Gioanni S.,Necker Enfants Malades Hospital | Mauriat P.,Haut Leveque Hospital | Pouard P.,Necker Enfants Malades Hospital
Critical Care | Year: 2011

Introduction: Experience with high-frequency oscillatory ventilation (HFOV) after congenital cardiac surgery is limited despite evidence about reduction in pulmonary vascular resistance after the Fontan procedure. HFOV is recommended in adults and children with acute respiratory distress syndrome. The aim of the present study was to assess associations between commencement of HFOV on the day of surgery and length of mechanical ventilation, length of Intensive Care Unit (ICU) stay and mortality in neonates and infants with respiratory distress following cardiac surgery.Methods: A logistic regression model was used to develop a propensity score, which accounted for the probability of being switched from conventional mechanical ventilation (CMV) to HFOV on the day of surgery. It included baseline characteristics, type of procedure and postoperative variables, and was used to match each patient with HFOV with a control patient, in whom CMV was used exclusively. Length of mechanical ventilation, ICU stay and mortality rates were compared in the matched set.Results: Overall, 3,549 neonates and infants underwent cardiac surgery from January 2001 through June 2010, 120 patients were switched to HFOV and matched with 120 controls. After adjustment for the delay to sternal closure, duration of renal replacement therapy, occurrence of pulmonary hypertension and year of surgery, the probability of successful weaning over time and the probability of ICU delivery over time were significantly higher in patients with HFOV, adjusted hazard ratios and 95% confidence intervals: 1.63, 1.17 to 2.26 (P = 0.004). and 1.65, 95% confidence intervals: 1.20 to 2.28 (P = 0.002) respectively. No association was found with mortality.Conclusions: When commenced on the day of surgery in neonates and infants with respiratory distress following cardiac surgery, HFOV was associated with shorter lengths of mechanical ventilation and ICU stay than CMV. © 2011 Bojan et al.; licensee BioMed Central Ltd.


Miladi L.,Necker Enfants Malades Hospital | Mousny M.,Cliniques Universitaires Saint Luc
European Spine Journal | Year: 2014

Introduction: Several different growing rod techniques have been described in the literature to treat progressive scoliosis in young children. Nevertheless, none of these techniques has shown a real superiority, and the rate of complications remains high. The purpose of this report is to describe an original fusionless method of treatment for this problem. Materials and methods: The 3 hooks-2 screws (H3S2) construct consists of a single 5.5 mm titanium rod with three hooks proximally and two monoaxial pedicle screws distally, and some extra length of rod located distally and/or proximally that can be used for future lengthenings. To date, a total of 103 H3S2 constructs have been performed in our institution. This paper reports the preliminary results on 38 patients, with a minimum follow-up of 2 years. Results: This procedure was found to be effective in maintaining scoliosis correction while allowing continued spinal growth and was associated with a low rate of complications. Conclusions: The H3S2 construct was found to have several advantages over the growing rod techniques as previously described in the literature. These include no need for post-operative bracing, fewer lengthening procedures and a lower rate of complications. © 2014 Springer-Verlag.


Duchatelet S.,French Institute of Health and Medical Research | Duchatelet S.,University of Paris Descartes | Hovnanian A.,French Institute of Health and Medical Research | Hovnanian A.,University of Paris Descartes | Hovnanian A.,Necker Enfants Malades Hospital
Orphanet Journal of Rare Diseases | Year: 2015

Résumé: Le syndrome d'Olmsted (SO) est une génodermatose rare et sévère, classiquement caractérisée par une kératodermie palmo-plantaire (KPP) bilatérale transgrédiente et mutilante associée à des plaques kératosiques périorificielles. Il existe une grande hétérogénéité clinique. Des anomalies des cheveux et des ongles, une leukokératose, des anomalies de la cornée et de fréquentes infections peuvent être associées. La douleur et le prurit sont variables, mais peuvent être sévères. La maladie débute généralement à la naissance ou pendant la petite enfance. Approximativement 73 cas ont été rapportés à travers le monde. La maladie touche les deux genres. La plupart des cas sont sporadiques, bien que des cas familiaux avec différents modes de transmission aient également été décrits. Des mutations du gène TRPV3 (Transient receptor potential vanilloid-3) ont récemment été identifiées dans les formes autosomiques dominante (mutations gain-de-fonction) et récessive. Des mutations du gène MBTPS2 (membrane-bound transcription factor protease, site 2) ont été rapportées dans une forme récessive liée à l'X. Le diagnostic est essentiellement clinique, reposant sur l'association d'une KPP sévère et de kératoses périorificielles∈; mais il peut être difficile chez les patients ayant une présentation incomplète ou des symptômes atypiques. Le SO doit être différencié des autres KPP sévères telles les syndromes de Vohwinkel, de Clouston, de Papillon-Lefèvre ou de Haim-Munk, le Mal de Meleda, la pachyonychie congénitale, la tyrosinémie de type II et l'acrodermatite entéropathique. Lorsque le diagnostic est difficile à établir, les études génétiques sont essentielles afin de rechercher une mutation des gènes TRPV3 ou MBTPS2. Cependant, d'autres gènes restent à identifier. Il n'existe à ce jour pas de traitement spécifique du SO. Les traitements actuels de l'hyperkératose comprennent essentiellement des émollients, kératolytiques, rétinoïdes et corticoïdes, locaux ou systémiques. La prise en charge spécifique de la douleur et du prurit représente un aspect important du traitement. La KPP massive et l'auto-amputation des doigts peuvent être très invalidants. Le développement de nouveaux traitements est crucial et attendu d'une meilleure compréhension des mécanismes pathologiques dela maladie. L'utilisation d'antagonistes de TRPV3 représenterait une nouvelle option thérapeutique prometteuse.Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, but which shows considerable clinical heterogeneity. The disease starts usually at birth or in early childhood. About 73 cases have been reported worldwide. OS is observed in both sexes, although male cases are more frequent. The most suggestive symptoms associate PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe. Most of reported OS cases are sporadic, although familial cases with different mode of inheritance were also described. Mutations in TRPV3 (Transient receptor potential vanilloid-3) gene have recently been identified as a cause of autosomal dominant (gain-of-function mutations) or recessive OS. Mutations in MBTPS2 (membrane-bound transcription factor protease, site 2) gene were identified in a recessive X-linked form. The diagnosis relies mainly on clinical features associating severe PPK and periorificial keratotic plaques, but can be challenging in patients with incomplete phenotype or atypical features. OS has to be differentiated from other severe forms of PPK including Vohwinkel, Clouston, Papillon-Lefèvre or Haim-Munk syndromes, Mal de Meleda, pachyonychia congenita, Tyrosinemia type II and acrodermatitis enteropathica. When differential diagnoses are difficult to exclude, genetic studies are essential to search for a TRPV3 or MBTPS2 mutation. However, additional genes remain to be identified. No specific and satisfactory therapy is currently available for OS. Current treatments of hyperkeratosis (mainly emollients, keratolytics, retinoids or corticosteroids), either topical or systemic, are symptomatic and offer only temporary partial relief. Specific management of pain and itching is important to reduce the morbidity of the disease. The disease is debilitating and progressive keratoderma and auto-amputation of digits can prevent patients from grasping and walking, and confine them to a wheelchair. New therapeutic options are therefore crucial and are expected from a better understanding of the disease mechanisms. The use of TRPV3 antagonists would represent such a targeted and potentially powerful strategy. © 2015 Duchatelet and Hovnanian; licensee BioMed Central.


Polak M.,Necker Enfants Malades Hospital | Polak M.,University of Paris Pantheon Sorbonne | Luton D.,University Paris Diderot
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2014

Advances in prenatal imaging techniques and in fetal hormonology now allow for identification of disorders of thyroid function in the fetus. These can potentially be treated in utero by giving drugs to the mother. This review shows the feasibility of in utero treatment of fetal thyroid disorders, either indirectly by treating the mother or by giving the necessary drugs directly to the fetus. For goitrous fetal hypothyroidism leading to hydramnios, repeated intra-amniotic injections of thyroxine have been reported to decrease the size of the fetal thyroid. Experience with such procedures is limited but positive. The risk that direct in utero treatment of the fetus may provoke premature labor or cause infection should be carefully evaluated. In women with Graves' disease, autoimmune fetal hyperthyroidism can generally be treated in a noninvasive way by optimizing treatment of the mother, such as by increasing the dose of antithyroid drugs. Follow-up of the efficacy and the possible long-term consequences of medical interventions to normalize thyroid function of the fetus are of great importance. Specialized care of the fetus should be provided by skilled teams with extensive experience in prenatal care. © 2013 Elsevier Ltd. All rights reserved.

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