P Evrard

Hôpital Universitaire Robert Debré, Lutetia Parisorum, Île-de-France, France

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Publications (114)250.61 Total impact

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    ABSTRACT: To define the contribution of prenatal investigation and evaluate the prognosis of isolated mild ventriculomegaly (IMV). Retrospective study. University hospital between January 1992 and December 2002. One hundred and sixty-seven cases of prenatal unilateral or bilateral IMV without any associated anomaly at the time of initial diagnosis. Complementary investigations were performed: amniocentesis with karyotyping, screening for viruses and acetylcholinesterase electrophoresis, magnetic resonance imaging (MRI), and ultrasonography every 3-4 weeks. Results of prenatal investigations, pregnancy outcome, and postnatal psychomotor development. IMV was diagnosed around 26.5 weeks. Amniocentesis revealed four chromosomal anomalies and two cytomegalovirus infections. MRI diagnosed brain-associated anomalies in 15 cases and ultrasonographic monitoring highlighted malformations not initially diagnosed in 28 cases. Termination of pregnancy (TOP) was considered in 21 pregnancies (12.6%). Indications were aneuploidy, fetal infectious disease or associated malformations. In women for whom a TOP was considered, consanguinity, fetus of female sex and frontal horn enlargement were statistically more frequent, ventriculomegaly was more often bilateral and asymmetrical, atrial width, and the rate of progressive ventricular enlargement were significantly higher. One hundred and one children with prenatal IMV were assessed between 19 and 127 months (mean age 54.68 +/- 2.87 months). Twelve children had neurological disease or psychomotor delay and 89 children had a normal psychomotor development. Poor neurological outcome was more often associated with atrial width greater than or equal to 12 mm, asymmetrical bilateral enlargement, and progression of the ventriculomegaly. The detection of IMV raises the question of the child's psychomotor development and justifies meticulous prenatal investigation. In addition to associated anomalies, three criteria are often associated with an unfavourable outcome: atrial width greater than 12 mm, progression of the enlargement, and asymmetrical and bilateral ventriculomegaly.
    BJOG An International Journal of Obstetrics & Gynaecology 10/2006; 113(9):1072-9. DOI:10.1111/j.1471-0528.2006.01050.x · 3.86 Impact Factor
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    ABSTRACT: Aicardi-Goutieres syndrome, first described in 1984, is a progressive infantile familial encephalopathy featuring cerebral calcifications, mainly of the basal ganglia, cerebral white matter abnormalities and cerebrospinal fluid lymphocytosis. Most of the patients present with severe developmental retardation, microcephaly, abnormal eye movements, pyramidal tract signs, and prominent dystonic movements. An elevated level of interferon-alpha in the CSF is a constant feature, particularly during the first stages of the disease course. One locus has been mapped on chromosome 3p21 in about half of the families so far studied. and results. We report two new French cases and discuss the limits of the clinical syndrome, the differential diagnosis and issues raised by the pathophysiological mechanisms involved. The major concern is to separate this condition from intrauterine infections because of the genetic and therapeutic consequences. A number of other questions remain unanswered. For example, we still do not know today at what age the absence of features like CSF lymphocytosis, and possibly absence of calcifications, rules out the diagnosis of the condition. The origin of the vasculitis lesions is not known, but seems to be related to dysregulation of interferon production and secretion. Currently about 75 patients have been reported, even though many more probably exist. The study of this syndrome can contribute to the understanding of some mechanisms of CNS calcification and in a broader perspective to that of chronic encephalopathies with dysregulation of immune mechanisms.
    Revue Neurologique 05/2005; 161(4):445-50. · 0.60 Impact Factor
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    ABSTRACT: Introduction Aicardi-Goutières syndrome, first described in 1984, is a progressive infantile familial encephalopathy featuring cerebral calcifications, mainly of the basal ganglia, cerebral white matter abnormalities and cerebrospinal fluid lymphocytosis. Most of the patients present with severe developmental retardation, microcephaly, abnormal eye movements, pyramidal tract signs, and prominent dystonic movements. An elevated level of interferon-alpha in the CSF is a constant feature, particularly during the first stages of the disease course. One locus has been mapped on chromosome 3p21 in about half of the families so far studied. Patients and results We report two new French cases and discuss the limits of the clinical syndrome, the differential diagnosis and issues raised by the pathophysiological mechanisms involved. The major concern is to separate this condition from intrauterine infections because of the genetic and therapeutic consequences. A number of other questions remain unanswered. For example, we still do not know today at what age the absence of features like CSF lymphocytosis, and possibly absence of calcifications, rules out the diagnosis of the condition. The origin of the vasculitis lesions is not known, but seems to be related to dysregulation of interferon production and secretion. Conclusion Currently about 75 patients have been reported, even though many more probably exist. The study of this syndrome can contribute to the understanding of some mechanisms of CNS calcification and in a broader perspective to that of chronic encephalopathies with dysregulation of immune mechanisms.
    Revue Neurologique 04/2005; 161(4):445-450. DOI:10.1016/S0035-3787(05)85074-X · 0.60 Impact Factor
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    ABSTRACT: In the management of autoimmune myasthenia, thymectomy is recognized as effective surgical therapy. The necessity of complete radical thymectomy to achieve maximal improvement has been emphasized. Video-assisted thoracoscopic surgery has been successfully used for thymectomy in adults, and more recently in children, and has been described as achieving the same radicality and functional improvement as median sternotomy or as transcervical thymectomy. The aim of this work is to report our first thoracoscopic experience in this indication. Patients with myasthenia gravis on anticholinesterase drugs and/or steroids are discussed for surgery in case of clinical deterioration despite increasing doses of medication or in case of no improvement. We decided to perform thoracoscopic thymectomies by a left-sided approach. Preoperative localization of thymic tissue is done by a thoracic CT exam. Patients are placed on their right side with a thoracic tilt under the thorax. Four thoracoscopic ports are used, a 10-mm for the camera and three 5-mm operating ports. The left lung was collapsed by selective intubation (double-lumen endotrachial intubation). Two boys, 7.5 and 14 years old, were addressed by the department of neurology for radical thymectomy. They presented an ocular myasthenia gravis for 2 years and a mild general myasthenia gravis for 7 years. The operative times were 120 and 240 min. There was no intraoperative or postoperative complication. Duration of thoracic drainage was 2 days. The children were discharged on the third postoperative day. For the second procedure, an ultrasound exam during surgery was necessary to localize the thymus exactly, thus enabling its complete resection without the need for a conversion. The follow-up is 19 and 7 months with a clinical improvement enabling the diminution of medication for both children, the end of ptosis for the first child, and the general improvement of muscle strength for the second. Thoracoscopic thymectomy in children with juvenile myasthenia gravis seems to offer a complete surgical resection, as do open techniques. In case of difficulties in finding the thymus, an ultrasound exam is feasible to enable complete resection. The left-sided thoracoscopic approach gives a good mediastinal and cervical exposition. Furthermore, being less painful in the postoperative period, it presents a less pronounced impairment of pulmonary function, and it presents good cosmetic effect.
    Surgical Endoscopy 02/2005; 19(1):140-2. DOI:10.1007/s00464-004-9039-y · 3.31 Impact Factor
  • Revue Neurologique 11/2004; 24:146-147. DOI:10.1016/S0242-6498(04)94163-6 · 0.60 Impact Factor
  • P Evrard, A Arzimanoglou
    Archives de Pédiatrie 06/2003; 10 Suppl 1:46s-49s. · 0.41 Impact Factor
  • P Evrard, A Arzimanoglou
    Archives de Pédiatrie 05/2003; 10. DOI:10.1016/S0929-693X(03)90377-0 · 0.41 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate whether deficient peroxisomal beta-oxidation is causally involved in the neuronal migration defect observed in Pex5 knockout mice. These mice are models for Zellweger syndrome, a peroxisome biogenesis disorder. Neocortical development was evaluated in mice carrying a partial or complete defect of peroxisomal beta-oxidation at the level of the second enzyme of the pathway, namely, the hydratase-dehydrogenase multifunctional/bifunctional enzymes MFP1/L-PBE and MFP2/D-PBE. In contrast to patients with multifunctional protein 2 deficiency who present with neocortical dysgenesis, impairment of neuronal migration was not observed in the single MFP2 or in the double MFP1/MFP2 knockout mice. At birth, the double knockout pups displayed variable growth retardation and about one half of them were severely hypotonic, whereas the single MFP2 knockout animals were all normal in the perinatal period. These results indicate that in the mouse, defective peroxisomal beta-oxidation does not cause neuronal migration defects by itself. This does not exclude that the inactivity of this metabolic pathway contributes to the brain pathology in mice and patients with complete absence of functional peroxisomes.
    Journal of Neuropathology and Experimental Neurology 05/2002; 61(4):368-74. · 4.37 Impact Factor
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    ABSTRACT: Other studies have shown that caffeine accelerates telencephalic vesicle evagination in early post-implantation mouse embryos. The present study examines the effect of caffeine on gene modulation in post-implantation mouse embryos. Using mRNA differential display, we observed that caffeine increased gene expression of the regulatory subunit (RI alpha) of cAMP-dependent protein kinase (PKA). RT--PCR analysis confirmed an increase in expression of this gene in caffeine-exposed embryos when compared with saline-treated controls. Using a fluorescent substrate of PKA, we found that PKA activity in the presence of cAMP was lower in caffeine-treated embryos than in controls. Treatment with H89 and PKI(12-24)amide, two inhibitors of PKA activity, mimicked the effects of caffeine on telencephalic vesicle formation. Together these data suggest that in early post-implantation mouse embryos caffeine modulates gene expression of the RI alpha subunit of PKA and that caffeine-induced inhibition of PKA activity plays a role in early telencephalic evagination.
    Cerebral Cortex 05/2001; 11(4):343-9. DOI:10.1093/cercor/11.4.343 · 8.31 Impact Factor
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    M Spedding, P Evrard, P Gressens
    Developmental medicine and child neurology. Supplement 04/2001; 86:10-2. DOI:10.1111/j.1469-8749.2001.tb04138.x
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    ABSTRACT: Periventricular leukomalacia (PVL) is the main cause of neurologic handicap in pre-term infants. The understanding of cellular and molecular mechanisms leading to white matter damage is critical for development of innovative therapeutic strategies for PVL. The pathogenesis of PVL remains unclear but possibly involves glutamate excitotoxicity as an important molecular pathway. We previously described a neonatal mouse model of excitotoxic white matter lesion mimicking human PVL. In the present study, we used this experimental tool to investigate the cellular populations and the glutamate receptor subtypes involved in excitotoxic white matter lesions. Combined immunohistochemical, electron microscopic, and cell death detection data revealed that microglial activation and astrocytic death were the primary responses of white matter to excitotoxic insult. In vitro experiments suggested that microglia activated by ibotenate released soluble factors that kill astrocytes. The use of selective agonists and antagonists of glutamate receptors revealed that N-methyl-D-aspartate (NMDA) receptor activation was essential and sufficient to produce cystic white matter lesions. NMDA receptor immunohistochemistry labeled microglial cells in the neonatal periventricular white matter. The developing white matter displayed a window of sensitivity to excitotoxic damage that was paralleled by the transient presence of NMDA receptor-expressing white matter cells. Assuming that similar pathophysiologic mechanisms are present in human pre- term infants, microglia and NMDA receptors could represent key targets for treatment of PVL.
    Brain Pathology 02/2001; 11(1):56-71. DOI:10.1111/j.1750-3639.2001.tb00381.x · 4.35 Impact Factor
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    ABSTRACT: Epileptic seizures are a common feature in Menkes disease, an X-linked genetic disorder of copper metabolism. Details of type of seizures are rarely reported. We report the evolution of infantile spasms in two patients with Menkes disease and the relation with subcutaneous administration of copper-histidine.
    Epileptic disorders: international epilepsy journal with videotape 01/2001; 2(4):227-30. · 0.90 Impact Factor
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    ABSTRACT: Intracerebral administration of ibotenate produces, through activation of N-methyl-D-aspartate (NMDA) receptors, neuronal heterotopias in the newborn hamster neocortex: high doses of ibotenate induce periventricular and subcortical neuronal heterotopias, while low doses of ibotenate produce intracortical heterotopias and molecular layer ectopias. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are closely related peptides with neurotrophic properties. They share common VPAC1 and VPAC2 receptors, which use cAMP as a second messenger. Previous studies have shown that VIP prevents excitotoxic neuronal death and exacerbates glutamate-induced c-fos neuronal expression. In order to gain new insight into the molecular control of neuronal migration, the present study examined the effects of VIP and PACAP on ibotenate-induced heterotopias in the newborn hamster. Co-treatment with VIP and a high dose of ibotenate produced a pattern of neuronal heterotopias similar to the one observed in animals treated with low doses of ibotenate alone. Pups co-injected with a low dose of ibotenate and a VIP antagonist displayed cortical dysgeneses similar to those observed in animals treated with high doses of ibotenate alone. The modulating effects of VIP on excitotoxin-induced heterotopias were mimicked by forskolin, PACAP, and by a specific VPAC2 receptor agonist but not by a VPAC1 agonist, and were blocked by a protein kinase A (PKA) inhibitor. Taken together, these data suggest that VIP and PACAP can attenuate ibotenate-induced heterotopias in newborn hamster and that this effect is mediated by the VPAC2 receptor utilizing the cAMP-PKA pathway.
    Journal of Neuropathology and Experimental Neurology 01/2001; 59(12):1051-62. · 4.37 Impact Factor
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    ABSTRACT: Cortical dysgenesia are a heterogenous group of genetic or acquired disturbances of cortical development which, due to the enormous progress in modern neuroimaging techniques, are increasingly recognized in association with a variety of clinical disorders. The spectrum of clinical manifestations, depending on type and extent of the alterations, includes severe mental retardation and epilepsy as well as neuropsychological deficits and some psychiatric disorders. Although pathogenesis and pathophysiology of cortical dysgenesis are still not fully understood, the recent discovery of responsible genes, growth factors, neurotransmitters, and exogenous factors sheds light on elementary mechanisms. The development of animal models mimicking different types of human cortical malformations helped to increase further the understanding of functional consequences of focal cortical dysgenesis. Several studies on these models reveal widespread alterations of cortical connectivity and excitability which are probably of crucial importance in different clinical disorders.
    Der Nervenarzt 05/2000; 71(4):238-48. · 0.86 Impact Factor
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    ABSTRACT: Kortikale Dysgenesien umfassen eine heterogene Gruppe von angeborenen und erworbenen Störungen der Hirnrindenentwicklung, die durch die enormen Fortschritte der modernen bildgebenden Verfahren immer häufiger im Zusammenhang mit verschiedenen Krankheitsbildern diagnostiziert werden. Das Spektrum dieser Krankheitsmanifestationen reicht dabei je nach Typ und Ausmaß der Veränderungen von schweren mentalen Retardierungen über epileptische Anfallsleiden bis hin zu isolierten neuropsychologischen Defiziten und psychiatrischen Erkrankungen. Obwohl Pathogenese und Pathophysiologie der kortikalen Dysgenesien derzeit noch weitestgehend ungeklärt sind, konnten in den vergangenen Jahren durch die Entdeckung einiger verantwortlicher Gene, Wachstumsfaktoren, Neurotransmitter und exogener Faktoren eine Reihe von pathophysiologischen Entstehungsmechanismen aufgeklärt werden. Die Entwicklung von tierexperimentellen Modellen, die verschiedene Typen menschlicher kortikaler Malformationen widerspiegeln, ermöglichte darüber hinaus ein besseres Verständnis der funktionellen Auswirkungen fokaler kortikaler Dysgenesien. Dabei zeigte sich, dass fokale kortikale Dysgenesien zu ausgedehnten Veränderungen der kortikalen Konnektivität und Errregbarkeit führen, die bei der Entstehung der verschiedenen Krankheitsbilder vermutlich von entscheidender Bedeutung sind. Cortical dysgenesia are a heterogenous group of genetic or acquired disturbances of cortical development which, due to the enormous progress in modern neuroimaging techniques, are increasingly recognized in association with a variety of clinical disorders. The spectrum of clinical manifestations, depending on type and extent of the alterations, includes severe mental retardation and epilepsy as well as neuropsychological deficits and some psychiatric disorders. Although pathogenesis and pathophysiology of cortical dysgenesis are still not fully understood, the recent discovery of responsible genes, growth factors, neurotransmitters, and exogenous factors sheds light on elementary mechanisms. The development of animal models mimicking different types of human cortical malformations helped to increase further the understanding of functional consequences of focal cortical dysgenesis. Several studies on these models reveal widespread alterations of cortical connectivity and excitability which are probably of crucial importance in different clinical disorders.
    Der Nervenarzt 02/2000; 71(4):238-248. DOI:10.1007/s001150050553 · 0.86 Impact Factor
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    ABSTRACT: Many prenatal and perinatal factors are hypothesized to play a role in the cause of cerebral palsy (CP). Epidemiological data implicate maternal-fetal infection and associated increase in circulating cytokines. Murine model data suggest that excitotoxic damage can produce pathological change in brain tissue consistent with lesions observed in CP. Specifically, on day 5 after birth, mouse pups injected with ibotenate, a glutamatergic analogue, develop transcortical necrosis and white matter cysts mimicking some human perinatal lesions associated with CP. The present study builds on this murine model to assess the modulating role of several cytokines on the development of excitotoxic lesions. Pups pretreated with interleukin (IL)-1beta, IL-6, IL-9, or tumor necrosis factor-alpha developed significantly larger ibotenate-induced cortical and white matter damage than controls; IL-4 did not produce such an effect. In a similar manner, IL-9-overexpressing transgenic pups developed ibotenate-induced brain lesions, which were significantly larger than those induced in nontransgenic control pups. Pretreatment with proinflammatory cytokines significantly increased neopallial microglial density without affecting astrocytic density; IL-9 or IL-4 did not produce a similar effect. To our knowledge, this is the first in vivo study to demonstrate that systemically administered proinflammatory cytokines and IL-9 exacerbate brain lesions that are similar to those found in human infants with CP.
    Annals of Neurology 02/2000; 47(1):54-63. DOI:10.1002/1531-8249(200001)47:13.0.CO;2-Y · 11.91 Impact Factor
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    C Bonnier, M C Nassogne, P Evrard
    American Journal of Psychiatry 08/1999; 156(7):1122-3. · 13.56 Impact Factor
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    ABSTRACT: Periventricular leukomalacia (PVL), a necrotic and often cystic lesion of the cerebral white matter occurring in very premature babies, is the leading cause of cerebral palsy in this population. Increased glutamate release and the excitotoxic cascade thus triggered may be critical factors in the development of PVL. The glutamatergic analog ibotenate injected intracerebrally into newborn mice produces white matter cysts that mimic human PVL. Concomitant injection of vasoactive intestinal peptide (VIP), a trophic factor, protects the white matter against excitotoxic lesions. The goal of the present study was to assess the protective properties of systemically injected VIP analogs against ibotenate-induced excitotoxic white matter lesions in newborn mice. VIP analogs were selected on the basis of their low susceptibility to endopeptidases and their potential ability to cross biological membranes. RO-25-1553, a long-lasting cyclic VIP analog, and stearyl-norleucine-VIP, a fatty derivative of VIP, reduced ibotenate-induced white matter cysts by up to 87% and 84%, respectively, when injected i.p. immediately after ibotenate. By comparison, i.p. coadministration of VIP and ibotenate was not protective against the excitotoxic insult. Furthermore, RO-25-1553 and stearyl-norleucine-VIP still induced significant neuroprotection of the developing white matter when injected systemically 8 and 12 h, respectively, after ibotenate, establishing these peptides as therapeutic agents in this murine model. VIP analogs may have therapeutic potential in human premature babies at high risk for PVL.
    Journal of Pharmacology and Experimental Therapeutics 04/1999; 288(3):1207-13. · 3.86 Impact Factor
  • G Lamboley, P Evrard, P Gressens
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    ABSTRACT: The glutamatergic agent ibotenate induces cortical plate and white matter lesions in the newborn mouse, mimicking brain lesions of the human neonate. In this model, co-treatment with ibotenate and a vasoactive intestinal peptide antagonist (VA) aggravates the excitotoxic lesions, suggesting a protective role of endogenous VIP. On the other hand, prenatal injection of VA is followed by a dramatic depletion of astrocytes in the neocortex. Since astrocytes produce numerous neuronotrophic agents, we studied the consequences of a decreased astrocytic density by prenatal VIP blockade on the excitotoxic brain lesions in newborn mice. Pregnant females were pre-treated with VA during the last 2 days of gestation and ibotenate was intracerebrally injected on postnatal day (P) 2 or P5. When compared to controls, pups pre-treated with VA and injected with ibotenate at P2 displayed a significant reduction of the white matter lesion size while cortical plate lesion was not affected. This protective effect disappeared when ibotenate was injected at P5. White matter protection by VA pre-treatment did not seem to be linked to the decreased astrocytic density since, i) this astrocytic paucity concerns only superficial cortical layers and does not affect white matter, ii) protective effects are only observed at P2 while astrocytic density reduction is observed at P2 and P5. This white matter protection could be secondary to an up-regulation of VIP receptors: an increased density of VIP receptors, which was described in other developmental models following VA treatment, could increase the efficacy of the endogenous VIP after an excitotoxic insult.
    Archives de Pédiatrie 02/1999; 6(1):67-74. · 0.41 Impact Factor
  • European Journal of Paediatric Neurology 01/1999; 3(6). DOI:10.1016/S1090-3798(99)91000-0 · 1.93 Impact Factor

Publication Stats

2k Citations
250.61 Total Impact Points

Institutions

  • 1996–2006
    • Hôpital Universitaire Robert Debré
      • Service de Néphrologie Pédiatrique
      Lutetia Parisorum, Île-de-France, France
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 1999
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1990–1998
    • Cliniques Universitaires Saint-Luc
      • • Division of Pediatric Neurology
      • • Department of Medical Imaging
      Bruxelles, Brussels Capital Region, Belgium
  • 1978–1995
    • Catholic University of Louvain
      • Department of Nephrology
      Лувен-ла-Нев, Walloon, Belgium
  • 1994
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 1992
    • University of California, San Francisco
      San Francisco, California, United States