C Lacroix

University of Paris-Est, La Haye-Descartes, Centre, France

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Publications (136)502.57 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To compare the natural history of Familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. Methods: We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies and muscle biopsies are reported. We also conducted a comprehensive literature review in order to further determine the range of phenotypic expression. Results: By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr and LateVal30Met FAP showed more rapid and severe disease progression: onset of gait disorders was three times more rapid (p<0.0001), the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p<0.0001). Median survival was much shorter in Ile107Val and LateVal30Met FAP (p=0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p=0.0005), difficult identification of amyloid deposits in nerve and muscle biopsies. Interpretation: Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by the frequent large-fibers involvement, associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). This article is protected by copyright. All rights reserved.
    Annals of Neurology 09/2015; DOI:10.1002/ana.24519 · 9.98 Impact Factor
  • 43rd Annual Meeting of the Child-Neurology-Society; 10/2014
  • Joint Congress of European Neurology; 05/2014
  • Joint Congress of European Neurology; 05/2014
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    ABSTRACT: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.
    Neuro-Oncology 04/2014; 16(9). DOI:10.1093/neuonc/nou047 · 5.56 Impact Factor
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  • C. Lacroix · C. Adam
    Revue Neurologique 04/2014; 170:A189. DOI:10.1016/j.neurol.2014.01.505 · 0.66 Impact Factor
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    ABSTRACT: The association of Charcot-Marie-Tooth (CMT) disease with renal dysfunction is uncommon but has long been recognized in several families. Recently, mutations in the INF2 gene, which encodes inverted formin-2, were identified in patients with focal segmental glomerulosclerosis and a dominant intermediate form of CMT (CMTDIE, OMIM #614455). We describe the pathologic lesions of nerve biopsies from 6 patients with INF2-related CMTDIE. There were 4 females and 2 males; ages were from 12 to 47 years; durations between neuropathy onset and biopsy were from 2 to 37 years. Clinical phenotypes were similar to those seen in other forms of CMT disease, but there was always an associated proteinuria (and later renal failure). Motor median nerve conduction velocities were in the range of intermediate CMT disease. Pathologic lesions suggested chronic demyelination and remyelination associated with progressive axonal loss. By electron microscopy, we observed unusual whorl-like proliferations of flattened Schwann cell cytoplasm and anomalies of unmyelinating Schwann cell cytoplasm with supernumerary elongated extensions similar to those described in CMT4C. We also observed abnormal accumulation of β-actin in the cytoplasm of Schwann cells. Our results suggest that these lesions reflect a global disorder of the actin cytoskeleton in Schwann cells and that CMTDIE is the first peripheral nerve disorder associated with a Schwann cell actinopathy.
    01/2014; 73(3). DOI:10.1097/NEN.0000000000000047
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    ABSTRACT: Non-syndromic arthrogryposis multiplex congenita (AMC) is characterized by multiple congenital contractures resulting from reduced fetal mobility. Genetic mapping and whole exome sequencing were performed in 31 multiplex and/or consanguineous undiagnosed AMC families. Although this approach identified known AMC genes, we here report pathogenic mutations in two new genes. Homozygous frameshift mutations in CNTNAP1 were found in four unrelated families. Patients showed a marked reduction in motor nerve conduction velocity (<10 m/sec) and transmission electron microscopy (TEM) of sciatic nerve in the index cases revealed severe abnormalities of both nodes of Ranvier width and myelinated axons. CNTNAP1 encodes CASPR, an essential component of node of Ranvier domains which underly saltatory conduction of action potentials along myelinated axons, an important process for neuronal function. A homozygous missense mutation in Adenylate Cyclase 6 gene (ADCY6) was found in another family characterized by a lack of myelin in the Peripheral Nervous System (PNS) as determined by TEM. Morpholino knockdown of the zebrafish orthologs led to severe and specific defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6 encodes a protein that belongs to adenylate cyclase family responsible for the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and upregulates myelinating signals. Our data indicate an essential and so far unknown role of ADCY6 in PNS myelination likely through the cAMP pathway. Mutations of genes encoding proteins of Ranvier domains or involved in myelination of Schwann cells are responsible for novel and severe human axoglial diseases.
    Human Molecular Genetics 12/2013; 23(9). DOI:10.1093/hmg/ddt618 · 6.39 Impact Factor
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    ABSTRACT: Domino liver transplantation (DLT) has become an accepted procedure designed to address problems with organ limited supply. However, cases of acquired amyloid neuropathy are increasingly being recognized following this procedure. Until now, only one patient had undergone liver retransplantation and follow-up findings were not reported. We describe the case of a 72-year-old patient with partial recovery from acquired amyloid neuropathy following retransplantation with a deceased donor 7 years after DLT performed for end-stage liver disease. His clinical and paraclinical improvement is described, and the impact of this case on the indication for a domino procedure and the challenges linked to retransplantation are discussed.
    American Journal of Transplantation 08/2013; 13(10). DOI:10.1111/ajt.12378 · 5.68 Impact Factor
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    ABSTRACT: Abstract Objective: Familial amyloid polyneuropathy (FAP) is typically a predominantly sensory and autonomic neuropathy with progressive and late motor involvement leading to death within 10 years. Recently, prognosis was transformed with liver transplantation. Methods: We report an atypical sporadic pure motor and bulbar neuropathy initially mistaken for amyotrophic lateral sclerosis (ALS) in a 50-year-old Malian man. Results: The diagnostic procedure of this clinical purely motor and bulbar neuropathy disclosed amyloid deposits on nerve biopsy which led to the identification of a new Val93Met mutation of transthyretin. This case was also remarkable by its slow progression. Conclusions: This report confirms the motor phenotype of TTR-FAP. That should be considered in the differential diagnosis of motor neuron diseases in order to start accurate therapy.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 08/2013; 20(3). DOI:10.3109/13506129.2013.818535 · 2.01 Impact Factor
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    P Lozeron · M Théaudin · Z Mincheva · B Ducot · C Lacroix · D Adams
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    ABSTRACT: The aim of this study was to assess the effect of Tafamidis, which slows the progression of early stages of Met30 transthyretin (TTR) familial amyloidosis polyneuropathy (FAP) in more advanced cases. The study was a prospective, non-randomized controlled trial carried out at the French national reference centre for FAP with follow-up at 1 year. Thirty-seven consecutive Met30-TTR-FAP patients were enrolled between December 2009 and July 2011, with NIS-LL (Neuropathy Impairment Score-lower limbs) > 10 and Karnofsky score > 60. Their mean (SD) age was 56.4 (19) years. Seventy-seven per cent of patients had a walking disability. Seven patients (19%) were withdrawn for adverse effects. The primary study outcome measurements, planned before data collection began, were NIS-LL and NIS-UL (upper limbs) scores and disability scores. Of the 37 patients entered into the study, 29 were evaluated at 6 months and 13 at 12 months. During the first 6 months of treatment, the mean progression of NIS-LL score was 4.8 and was similar to that during the period before treatment. Among the 45% of patients without NIS-LL progression, the NIS-UL score worsened in 55%. During the first year, 55% deteriorated with respect to disability and 38% with respect to NIS only; only two patients (7%) remained stable. Four (out of 20; 20%) patients who were previously stage 1 reached stage 2 (walking with aid) after this period. Two out of nine patients who were initially normotensive developed orthostatic hypotension. There were a total of 19 adverse events, including four febrile urinary tract infections and three severe diarrhoeas, with faecal incontinence in two. In most patients with advanced Met30 TTR-FAP, Tafamidis is not able to stop disease progression, in respect of both NIS-LL and disability. Other anti-amyloid medicines should be assessed in this context.
    European Journal of Neurology 07/2013; 20(12). DOI:10.1111/ene.12225 · 4.06 Impact Factor
  • G. Beaudonnet · C. Denier · C. Lacroix · A. Slama · D. Adams
    Revue Neurologique 04/2013; 169:A42. DOI:10.1016/j.neurol.2013.01.091 · 0.66 Impact Factor
  • B. Yalo · M. Theaudin · Z. Mincheva · C. Lacroix · D. Adams
    Revue Neurologique 04/2013; 169:A21–A22. DOI:10.1016/j.neurol.2013.01.043 · 0.66 Impact Factor
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    ABSTRACT: Candida spp. are responsible for severe infections in immunocompromised patients and those undergoing invasive procedures. The accurate identification of Candida species is important because emerging species can be associated with various antifungal susceptibility spectra. Conventional methods have been developed to identify the most common pathogens, but have often failed to identify uncommon species. Several studies have reported the efficiency of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of clinically relevant Candida species. In this study, we evaluated two commercially available MALDI-TOF systems, Andromas™ and Bruker Biotyper™, for Candida identification in routine diagnosis. For this purpose, we investigated 1383 Candida isolates prospectively collected in eight hospital laboratories during routine practice. MALDI-TOF MS results were compared with those obtained using conventional phenotypic methods. Analysis of rDNA gene sequences with internal transcribed regions or D1-D2 regions is considered the reference standard for identification. Both MALDI-TOF MS systems could accurately identify 98.3% of the isolates at the species level (1359/1383 for Andromas™; 1360/1383 for Bruker Biotyper™) vs. 96.5% for conventional techniques. Furthermore, whereas conventional methods failed to identify rare or emerging species, these were correctly identified by MALDI-TOF MS. Both MALDI-TOF MS systems are accurate and cost-effective alternatives to conventional methods for mycological identification of clinically relevant Candida species and should improve the diagnosis of fungal infections as well as patient management.
    Clinical Microbiology and Infection 03/2013; 20(2). DOI:10.1111/1469-0691.12210 · 5.77 Impact Factor
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    ABSTRACT: L’identification des champignons filamenteux, moisissures et dermatophytes, repose actuellement sur l’étude morphologique macroscopique et microscopique des colonies et, par conséquence, sur l’expérience du mycologue. Cette approche longue et fastidieuse, souvent imprécise, est incompatible avec les exigences actuelles de diagnostic des infections fongiques. L’identification des champignons filamenteux par MALDI-TOF est un champ d’innovation en pleine expansion. Bien que très peu d’études soient encore disponibles, les premiers travaux ont montré que la spectrométrie de masse MALDI-TOF permet d’obtenir une identification précise des espèces de champignons filamenteux, y compris au sein des complexes d’espèces. La spectrométrie de masse MALDI-TOF représente ainsi le premier outil permettant une identification rapide, précise et standardisée des champignons filamenteux. Les bases de données actuellement disponibles doivent être désormais évaluées dans les différents laboratoires de mycologie cliniques et complétées afin d’élargir le spectre des espèces identifiées.
    Bio Tribune Magazine 12/2012; 40(1). DOI:10.1007/s11834-011-0064-6
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    ABSTRACT: The aim of this study was to describe misleading lower limb mono radiculopathy revealing peripheral nerve vasculitis. Retrospective review of eight patients with biopsy confirmed vasculitis presenting as mono-radicululopathy in a tertiary referral centre dedicated to patients with rare peripheral neuropathies. Patients presented with chronic (6/8) or acute (n = 2) radiculopathy in L4, L5 or S1 territories associated with subtle systemic signs. A diagnostic workup was performed because of secondary motor deficit, the absence of clear radicular compression or failure of initial treatment focused on pain relief. In all, nerve conduction studies showed signs of asymmetrical axonal peripheral neuropathy (mononeuritis multiplex). Necrotizing vasculitis was eventually confirmed by peripheral nerve biopsy. Biological markers of inflammation or eosinophilia were present in 5/8 and a progressive motor deficit (7/8) is suggestive of the diagnosis. Under steroid treatment, all patients improved during a mean of 2 years 6 months of follow-up (Mean Rankin score improvement 1.9 point), but five relapsed including three mononeuritis multiplex, and one had acral necrosis. Vasculitis presenting as LL radiculopathy is rare; EMG studies with signs of mononeuritis multiplex and nerve biopsy studies are useful for making the diagnosis.
    Internal and Emergency Medicine 10/2012; 8(7). DOI:10.1007/s11739-012-0858-x · 2.62 Impact Factor
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    David Adams · Pierre Lozeron · Catherine Lacroix
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    ABSTRACT: As amyloid neuropathies have benefited from recent major progress, this review is timely and relevant. The main recent articles on amyloid neuropathy cover its description, methods for diagnosis and therapies. Varied clinical presentations are described in transthyretin (TTR)-familial amyloidosis with polyneuropathy (FAP) and light chain amyloid neuropathy. Mass spectrometry is able to identify the biochemical nature of amyloidogenic protein in nerve biopsy and skin biopsy samples for diagnosis of small fiber polyneuropathy. Both nerve biopsy and TTR gene sequencing are important to identify sporadic cases of amyloid neuropathy. Nerve biopsy is useful in demonstrating the amyloid origin of neuropathies developing after domino liver transplant recipients. Liver transplantation improves long-term survival in Met30 TTR-FAP. Factors recognized as leading to cardiomyopathy progression or heart involvement after liver transplantation are late disease onset and fibril composition. Combined heart and liver transplantation is recommended in severe restrictive cardiomyopathy. Antiamyloid drugs are emerging: tafamidis, a TTR stabilizer, showed in a phase III controlled study its ability to slow stage 1 FAP progression. Other strategies are emerging for TTR-FAP (combination doxycycline-tauroursodeoxycholic acid, small interfering RNA, antisense oligonucleotide, monoclonal antibody antiserum amyloid P component). For light chain neuropathy, intensive chemotherapy may be helpful. There is better recognition of amyloid neuropathies, and hope for enrolling patients with FAP in future clinical trials testing new antiamyloid drugs.
    Current opinion in neurology 08/2012; 25(5):564-72. DOI:10.1097/WCO.0b013e328357bdf6 · 5.31 Impact Factor
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    ABSTRACT: We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.
    New England Journal of Medicine 06/2012; 366(24):2276-83. DOI:10.1056/NEJMoa1201356 · 55.87 Impact Factor
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    ABSTRACT: Familial amyloidosis with polyneuropathy (FAP) in France have a large genetic heterogeneity with 29 transthyretin (TTR) gene mutations; Met30-TTR is the most frequent one (62%); followed by Tyr77-TTR (11.8%) and Phe77-TTR (6.2%). Analysis of 60 FAP patients diagnosed during the period 2008-2010 showed amyloid polyneuropathy was initially suspected in only 38% patients. TTR Met30 of Portuguese ancestry is different from TTR Met30 of non Portuguese ancestry and other non Met30 variants in geographical distribution and clinical presentation. There are three additional phenotypes of the neuropathy including multifocal upper limbs neuropathy, ataxic polyneuropathy and motor neuropathy. Patients with Tyr77-TTR are characterized by a late onset (>50 years), frequent ataxic phenotype; they are localized mainly in north of France. The more frequent use of the TTR genetic tests and the French network for FAP will help in the future to improve diagnosis and care.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 06/2012; 19 Suppl 1(S1):61-4. DOI:10.3109/13506129.2012.685665 · 2.01 Impact Factor

Publication Stats

2k Citations
502.57 Total Impact Points


  • 2013
    • University of Paris-Est
      La Haye-Descartes, Centre, France
  • 2011–2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Cadi Ayyad University
      Maraksh, Marrakech-Tensift-Al Haouz, Morocco
  • 2009–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008–2012
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 1997–2012
    • Université Paris-Sud 11
      • Service de Pneumologie
      Orsay, Île-de-France, France
  • 1996–2012
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      • • Service de Neurologie Adultes
      • • Service de Neuroradiologie
      Lutetia Parisorum, Île-de-France, France
  • 2002–2009
    • Mercy Hospital St. Louis
      San Luis, Missouri, United States