C Tranchant

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasburg, Alsace, France

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Publications (265)976.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: La malattia di Lyme è un’infezione batterica legata alla presenza di Borrelia (B.) burgdorferi, essa stessa trasmessa all’uomo da un morso di zecca. La forma primaria che compare nei giorni successivi al morso è rappresentata dall’eritema migrante. Le forme neurologiche possono essere precoci nelle settimane che seguono il morso o più tardive. Le forme precoci sono dominate dalle meningoradicoliti spinali o craniche, dalle mieliti e dalle encefaliti acute. Più rare sono le encefaliti croniche, le vasculiti cerebrali o le polineuropatie croniche. La diagnosi si basa sul confronto dei dati clinici e laboratoristici. In effetti, la presenza di una sierologia di Lyme positiva in una regione di endemia non è sufficiente per porre la diagnosi. Così, alcuni quadri clinici, anche accompagnati da una sierologia di Lyme positiva, rimangono discussi: malattia del motoneurone, sindromi parkinsoniane e alterazioni cognitive croniche. La presenza di una sintesi intratecale di immunoglobuline G anti-B. burgdorferi è un elemento fondamentale della diagnosi, anche se essa può essere assente nelle forme molto precoci (meningoradicoliti) e nelle polineuropatie croniche. Il trattamento delle forme neurologiche si basa sul ceftriaxone 2 g/die per 21-28 giorni. La sindrome post-Lyme è attualmente molto discussa e non giustifica una ripresa del trattamento antibiotico. Al contrario, le reinfezioni restano possibili in caso di nuove esposizioni a Borrelia, e la prevenzione primaria (protezione cutanea) è raccomandata in una regione di endemia.
    EMC - Neurologia. 11/2014; 14(4).
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    ABSTRACT: To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders.
    Neurology 08/2014; · 8.30 Impact Factor
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    Journal of neurology. 08/2014;
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    ABSTRACT: The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion.
    Neurology 08/2014; · 8.30 Impact Factor
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    ABSTRACT: ANO10 mutations have been reported to cause a novel form of autosomal recessive cerebellar ataxia (ARCA). Our objective was to report 9 ataxic patients carrying 8 novel ANO10 mutations to improve the delineation of this form of ARCA and provide genotype-phenotype correlation.
    JAMA Neurology 08/2014; · 7.58 Impact Factor
  • Article: [Foreword].
    C Verny, C Tranchant
    Revue Neurologique 05/2014; 170(5):307-8. · 0.51 Impact Factor
  • H Puccio, M Anheim, C Tranchant
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    ABSTRACT: Friedreich ataxia (FRDA) is the most common hereditary autosomal recessive ataxia, but is also a multisystemic condition with frequent presence of cardiomyopathy or diabetes. It has been linked to expansion of a GAA-triplet repeat in the first intron of the FXN gene, leading to a reduced level of frataxin, a mitochondrial protein which, by controlling both iron entry and/or sulfide production, is essential to properly assemble and protect the Fe-S cluster during the initial stage of biogenesis. Several data emphasize the role of oxidative damage in FRDA, but better understanding of pathophysiological consequences of FXN mutations has led to develop animal models. Conditional knockout models recapitulate important features of the human disease but lack the genetic context, GAA repeat expansion-based knock-in and transgenic models carry a GAA repeat expansion but they only show a very mild phenotype. Cells derived from FRDA patients constitute the most relevant frataxin-deficient cell model as they carry the complete frataxin locus together with GAA repeat expansions and regulatory sequences. Induced pluripotent stem cell (iPSC)-derived neurons present a maturation delay and lower mitochondrial membrane potential, while cardiomyocytes exhibit progressive mitochondrial degeneration, with frequent dark mitochondria and proliferation/accumulation of normal mitochondria. Efforts in developing therapeutic strategies can be divided into three categories: iron chelators, antioxidants and/or stimulants of mitochondrial biogenesis, and frataxin level modifiers. A promising therapeutic strategy that is currently the subject of intense research is to directly target the heterochromatin state of the GAA repeat expansion with histone deacytelase inhibitors (HDACi) to restore frataxin levels.
    Revue Neurologique 04/2014; · 0.51 Impact Factor
  • Neurogenetics 04/2014; · 3.58 Impact Factor
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    ABSTRACT: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid. We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients. The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died. Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.
    Revue Neurologique 04/2014; · 0.51 Impact Factor
  • C. Tranchant
    Pratique Neurologique - FMC 04/2014; 5(2):140–144.
  • Pratique Neurologique - FMC 04/2014; 5(2):83.
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    ABSTRACT: IMPORTANCE Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown. OBJECTIVE To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias. DESIGN, SETTING, AND PARTICIPANTS We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale. EXPOSURE Myoclonus-dystonia with a proven SGCE mutation. MAIN OUTCOMES AND MEASURES We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores. RESULTS We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other forms of primary dystonia. Myoclonus-dystonia patients also shared some common pathophysiological features of dystonia, including enhanced responsiveness of the motor cortex to plasticity induction and abnormal response to cerebellar conditioning as tested by EBCC. CONCLUSIONS AND RELEVANCE Specific underlying dysfunctions are associated with the very particular clinical phenotype of M-D and make it a unique entity that stands apart from other primary dystonias.
    JAMA Neurology 03/2014; · 7.58 Impact Factor
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    ABSTRACT: Purpose: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. Methods: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. Results: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41±0.17 units per year vs. risperidone and 0.54±0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). Conclusions: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.
    PLoS ONE 01/2014; 9(1):e85430. · 3.53 Impact Factor
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    ABSTRACT: Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD. We recruited patients older than 18 years old who had a diagnosis of definite or probable sporadic CJD or genetic forms of the disease via Italian reference centres and the French national referral system. Patients were randomly assigned (ratio 1:1) to receive oral doxycycline (100 mg daily) or placebo under double-blind conditions from the day of randomisation to death. Centralised randomisation was done independently of enrolment or evaluation of patients using a minimisation method in Italy and a simple randomisation in France. Participants, caregivers, and clinicians were masked to group assignment. The primary efficacy variable was the survival time from randomisation. Interim analyses were planned to detect a significant effect of treatment as early as possible. This trial is registered with EudraCT, 2006-001858-27 for the Italian study and 2007-005553-34 for the French study. From April 12, 2007, to Aug 19, 2010, in Italy, and from Jan 30, 2009, to Jan 10, 2012, in France, 121 patients with CJD were enrolled in the study, 62 of whom were randomly assigned to the treatment group and 59 to the placebo group. The first interim analysis showed absence of superiority of doxycycline compared with placebo, and the trial was stopped for futility. Efficacy analyses did not show significant differences between patients treated with doxycycline and placebo with regard to survival times (HR 1·1, 95% CI 0·8-1·7, p=0·50). Serious adverse events were judged not to be related to treatment, whereas a relation was deemed probable or possible for five non-serious adverse events that occurred in each treatment group. Doxycycline at a dose of 100 mg per day was well tolerated but did not significantly affect the course of CJD, at variance with the results of previous observational studies. Our experience could be useful in the design of large multinational controlled trials of potential anti-prion molecules in this rare disease. Agenzia Italiana Farmaco, Italian Ministry of Health, AIEnP, and French Ministry of Health.
    The Lancet Neurology 01/2014; · 23.92 Impact Factor
  • H. Puccio, M. Anheim, C. Tranchant
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    ABSTRACT: L’ataxie de Friedreich (FRDA) est la plus fréquente des ataxies récessives, mais est également une maladie pluri systémique souvent compliquée de la survenue d’un diabète ou d’une cardiomyopathie. Elle est liée à une expansion de triplets GAA dans le gène FXN, responsable d’une baisse du taux de frataxine, une protéine mitochondriale impliquée dans le transport du fer, la formation des noyaux Fe-S et la biogenèse des mitochondries. Différents modèles animaux ont été développés pour tenter de préciser la physiopathologie de la FRDA, dominée par le stress oxydatif. Les modèles knock-out pour la frataxine reproduisent les signes cliniques de la maladie, alors que les modèles reproduisant l’extension des triplets GAA n’ont qu’un phénotype incomplet. Les modèles les plus performants reposent actuellement sur les cultures de cellules pluripotentes (iPSC) issues de patients FRDA. Les neurones dérivés de ces iPSC présentent une maturation retardée et un potentiel de membrane mitochondrial bas, alors que les iPSC cardiomyocytes développent des lésions mitochondriales. Ces modèles sont indispensables pour tester les différentes approches thérapeutiques : chélateurs du fer, antioxydants et/ou stimulants de la biogenèse mitochondriale, modificateurs du taux de frataxine. Une stratégie prometteuse est l’utilisation d’inhibiteurs des histone–déacytélases agissant sur les expansions GAA pour restaurer le taux de frataxine.
    Revue Neurologique 01/2014; · 0.51 Impact Factor
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    ABSTRACT: Introduction Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid. Method We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients. Results The average age at diagnosis was 39 years (range 27–65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28–65 years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n = 5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died. Conclusion Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.
    Revue Neurologique 01/2014; · 0.51 Impact Factor
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    Journal of Neurology 12/2013; · 3.58 Impact Factor
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    ABSTRACT: We previously localized a new form of recessive ataxia with generalized tonic-clonic epilepsy and mental retardation to a 19 Mb interval in 16q21-q23 by homozygosity mapping of a large consanguineous Saudi Arabian family. We now report the identification by whole exome sequencing of the missense mutation changing proline 47 into threonine in the first WW domain of the WW domain containing oxidoreductase gene, WWOX, located in the linkage interval. Proline 47 is a highly conserved residue that is part of the WW motif consensus sequence and is part of the hydrophobic core that stabilizes the WW fold. We demonstrate that proline 47 is a key amino acid essential for maintaining the WWOX protein fully functional, with its mutation into a threonine resulting in a loss of peptide interaction for the first WW domain. We also identified another highly conserved homozygous WWOX mutation changing glycine 372 to arginine in a second consanguineous family. The phenotype closely resembled the index family, presenting with generalized tonic-clonic epilepsy, mental retardation and ataxia, but also included prominent upper motor neuron disease. Moreover, we observed that the short-lived Wwox knock-out mouse display spontaneous and audiogenic seizures, a phenotype previously observed in the spontaneous Wwox mutant rat presenting with ataxia and epilepsy, indicating that homozygous WWOX mutations in different species causes cerebellar ataxia associated with epilepsy.
    Brain 12/2013; · 10.23 Impact Factor
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    ABSTRACT: Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.
    Journal of Neurology 11/2013; · 3.58 Impact Factor
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    ABSTRACT: La miastenia gravis è una malattia autoimmune, legata alla presenza di anticorpi diretti contro i recettori dell’acetilcolina. Malattia prevalentemente della donna giovane, essa è spesso associata ad anomalie del timo (iperplasia o timoma). La timectomia ha un suo posto nel trattamento multidisciplinare di questi pazienti, come complemento dei vari trattamenti farmacologici, offrendo dei tassi di remissione che variano dal 13% al 51% a cinque anni. Il bilancio preoperatorio deve permettere di adattare la strategia chirurgica, che differisce in funzione dei dati morfologici, e, se è sospettato un timoma, facendo preferire, allora, una sternotomia alle vie mini-invasive. Negli altri casi, devono essere proposte ai pazienti le vie d’accesso mini-invasive. Infatti, esse hanno mostrato un’efficacia uguale alle altre tecniche in letteratura e offrono dei vantaggi innegabili, in particolare in termini di sequele estetiche, in questi pazienti giovani.
    EMC - Tecniche Chirurgiche Torace. 11/2013; 17(1):1–10.

Publication Stats

2k Citations
976.85 Total Impact Points

Institutions

  • 2008–2014
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      • Department of Translational Medicine and Neurogenetics
      Strasburg, Alsace, France
  • 2004–2014
    • French Institute of Health and Medical Research
      • Institute of Genetics and Molecular and Cellular Biology
      Lutetia Parisorum, Île-de-France, France
  • 2000–2013
    • CHRU de Strasbourg
      Strasburg, Alsace, France
    • University Joseph Fourier - Grenoble 1
      Grenoble, Rhône-Alpes, France
  • 1989–2013
    • University of Strasbourg
      • Faculty of pharmaceutical sciences
      Strasburg, Alsace, France
  • 2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2003–2012
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2006–2011
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Régional Universitaire de Lille
      • Urology Service
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Toulouse
      • Département d’Urologie
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 1991–2006
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2001
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France