Thierry Maisonobe

Publications (43)203.68 Total impact

• Article: Sensory chronic inflammatory demyelinating polyneuropathy: An under-recognized entity?

  Xavier Ayrignac, Karine Viala, Régine Morizot Koutlidis, Guillaume Taïeb, Tanya Stojkovic, Lucille Musset, Jean-Marc Léger, Emmanuel Fournier, Thierry Maisonobe, Pierre Bouche
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  ABSTRACT: Introduction: Sensory chronic inflammatory demyelinating polyneuropathy (CIDP) can be difficult to diagnose. Method: We report 22 patients with chronic sensory polyneuropathy with ≥1 clinical sign atypical for chronic idiopathic axonal polyneuropathy (CIAP) but no electrodiagnostic criteria for CIDP. Results: Clinical signs atypical for CIAP were: sensory ataxia (59%), generalized areflexia (36%), cranial nerve involvement (32%), rapid upper limb involvement (40%), and age at onset ≤55 years (50%). Additional features were: normal sensory nerve action potentials (36%), abnormal radial/normal sural pattern (23%), abnormal somatosensory evoked potentials (SSEPs) (100%), elevated CSF protein (73%), and demyelinating features in 5/7 nerve biopsies. Over 90% of patients responded to immunotherapy. We conclude that all patients had sensory CIDP. Discussion: Sensory CIDP patients can be misdiagnosed as having CIAP. If atypical clinical/electrophysiologic features are present, we recommend performing SSEPs and CSF examination. Nerve biopsy should be restricted to disabled patients if other examinations are inconclusive. © 2013 Wiley Periodicals, Inc.
  Muscle & Nerve 02/2013; · 2.37 Impact Factor
• Article: Antisynthetase syndrome with anti-Jo1 antibodies in 48 patients: pulmonary involvement predicts disease-modifying antirheumatic drug use.

  Raluca Stanciu, Marguerite Guiguet, Lucile Musset, Diane Touitou, Catherine Beigelman, Aude Rigolet, Nathalie Costedoat-Chalumeau, Yves Allenbach, Baptiste Hervier, Odile Dubourg, Thierry Maisonobe, Jean-Luc Charuel, Anthony Behin, Serge Herson, Zahir Amoura, Philippe Grenier, Olivier Benveniste
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  ABSTRACT: To analyze the characteristics, outcomes, and predictive factors of disease-modifying antirheumatic drug (DMARD) use in 48 patients with antisynthetase syndrome [characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon (RP), and/or mechanic's hands] and the presence of anti-histidyl-transfer RNA synthetase (anti-Jo1) autoantibodies. Forty-eight patients (33 women, 15 men) who were anti-Jo1-positive referred to one center between 1998 and 2008 were analyzed retrospectively. The median age of disease onset was 43 years [interquartile range (IQR) 33-53 yrs]. The median followup was 5 years (IQR 2-8 yrs). At diagnosis, 81% of patients presented with myositis, 80% ILD, 77% arthralgia, 48% RP, and 21% mechanic's hands. During the followup, 14 patients (29%) had no need for DMARD, while 34 (71%) required DMARD. Patients with mechanic's hands (p=0.02) and higher creatine phosphokinase at diagnosis (median 6070 IU/l vs 1121 IU/l; p=0.002) were more likely to need DMARD. ILD, noted on computed tomography scan by a nonspecific interstitial pneumonia score, was lower in the group of patients with no DMARD need (4 vs 7; p=0.04). Twenty patients (44%) presented with a pulmonary aggravation (worsening of radiologic score of ILD and/or pulmonary function test results) leading to DMARD use. Nonspecific interstitial pneumonia score (7 vs 5; p=0.05) and total lung volume (57.5% vs 70%; p=0.02) values predicted pulmonary aggravation. Our study outlines the burden of chest involvement for the prognosis of antisynthetase syndrome in terms of patients' requirement for DMARD therapy.
  The Journal of Rheumatology 08/2012; 39(9):1835-9. · 3.69 Impact Factor
• Article: Inflammatory myopathies with anti-Ku antibodies: a prognosis dependent on associated lung disease.

  Aude Rigolet, Lucile Musset, Odile Dubourg, Thierry Maisonobe, Philippe Grenier, Jean-Luc Charuel, Anthony Behin, Serge Herson, Zahir Amoura, Olivier Benveniste
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  ABSTRACT: Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with inflammatory myopathies (IM). We studied the clinical, laboratory, and muscle histologic features of all anti-Ku-positive patients detected in our hospital during the last 10 years, as well as their treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of 20,600 sera positive for antinuclear antibodies), and complete data were available for 30 patients; 86.7% were female, mean age was 49 years (range, 20-73 yr). The most frequent clinical manifestations were arthralgia (77%) and Raynaud phenomenon (53%). Eleven (37%) patients had IM, 8 of them as part of an overlap syndrome defined as IM associated with connective autoimmune disease (5 systemic sclerosis [SSc], 2 Sjögren syndrome (SS), and 1 systemic lupus erythematosus [SLE]). Of 21 patients without IM, 19 had autoimmune diseases (including 6 SLE, 2 SSc, 2 SS, and 2 rheumatoid arthritis), 1 had bronchial neoplasia, and 1 had nephroangiosclerosis. Clinical features of the 9 patients with IM were myalgia (91%), proximal muscle weakness (89%), and dysphagia (36%). All had increased creatine kinase (median, 2210 U/L; range, 194-4073 U/L). Muscle biopsy showed necrosis, inflammation, and positive HLA class I immunostaining. Interstitial lung disease (ILD) was detected on computed tomography (CT) scan in 11 patients (37%) and was significantly more frequent in patients with IM (82% vs. 10.5%, p < 0.001). Fourteen (47%) patients required no immunosuppressive treatment or only a low corticosteroid dose (<15 mg/d, n = 3). A high dose of corticosteroids was more frequently administered in patients with IM (10/11 cases, 80% with associated ILD) than in patients without IM (4/19 cases, 0 with ILD). Complete muscle remission after steroids occurred in 73% of patients with IM. Lung disease was corticoresistant in 6 of 8 (75%) treated cases.Anti-Ku antibodies remain rarely detected, but their presence can be frequently associated with corticosensitive IM and severe, corticoresistant ILD.
  Medicine 03/2012; 91(2):95-102. · 4.35 Impact Factor
• Article: Characteristics of clinical and electrophysiological pattern of Charcot-Marie-Tooth 4C.

  Marion Yger, Tanya Stojkovic, Sandrine Tardieu, Thierry Maisonobe, Alexis Brice, Andoni Echaniz-Laguna, Yves Alembik, Samantha Girard, Cécile Cazeneuve, Eric Leguern, Odile Dubourg
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  ABSTRACT: To describe the clinical and electrophysiological features evoking CMT4C, an autosomal recessive (AR) form of Charcot-Marie-Tooth disease (CMT) due to mutations in the SH3TC2 gene, we screened the coding sequence of SH3TC2 gene in 102 unrelated patients with a demyelinating or intermediate CMT and a family history compatible with an AR transmission. We identified among this cohort 16 patients carrying two mutations in the SH3TC2 gene, but medical records finally analyzed 14 patients. We report clinical, electrophysiological, and molecular data of 14 patients (9 men, 5 women) with CMT4C. Mean age at examination was 43.6 years (median = 42.5). Among the 14 studied cases 6 had scoliosis as the presenting sign. Cranial nerve involvement affecting either the VIIIth, VIIth, XIIth or a combination of the IXth and Xth nerves was noted in 10 patients. Remarkably, 50% of the patients had proximal limb involvement at the time of examination. The hallmark of the electrophysiological study was the presence of probable conduction block and temporal dispersion. Thus the clinical and paraclinical spectrum of CMT4C can guide the clinician to perform analysis of the SH3TC2 gene.
  Journal of the Peripheral Nervous System 03/2012; 17(1):112-22. · 2.80 Impact Factor
• Article: Heterogeneous spectrum of neuropathies in Waldenström's macroglobulinemia: a diagnostic strategy to optimize their management.

  Karine Viala, Tanya Stojkovic, Anne-Violaine Doncker, Thierry Maisonobe, Timothée Lenglet, Gaëlle Bruneteau, Lucile Musset, Jean Neil, Jean-Marc Léger, Véronique Leblond
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  ABSTRACT: Neuropathy in Waldenström's macroglobulinemia (WM) is very heterogeneous. We retrospectively studied 40 patients with WM and neuropathy to analyze the different presentations and mechanisms encountered and to propose a diagnostic strategy. Twenty-five patients (62.5%) had axonal neuropathy, related to the following mechanisms: amyloid neuropathy (n = 5), cryoglobulinemic neuropathy (n = 5), neuropathy associated with tumoral infiltration (n = 2), vasculitic neuropathy (n = 2), a clinical motor neuropathy possibly of dysimmune origin (n = 6), or an unclassified mechanism (n = 5). A demyelinating pattern was observed in 15 patients, 10 having anti-myelin-associated glycoprotein (anti-MAG) antibodies and 5 having neuropathy related to chronic inflammatory demyelinating polyradiculoneuropathy. On the basis of these results, we propose a diagnostic strategy combining: (1) an EMG to distinguish between a demyelinating and an axonal pattern; (2) measurement of anti-MAG and anti-ganglioside antibodies; (3) screening for "red flag" features to orientate further investigations. This strategy may help clinicians to identify the mechanism of neuropathy in order to adapt the therapeutic strategy.
  Journal of the Peripheral Nervous System 03/2012; 17(1):90-101. · 2.80 Impact Factor
• Article: A phase I trial of adeno-associated virus serotype 1-γ-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C.

  Serge Herson, Faycal Hentati, Aude Rigolet, Anthony Behin, Norma B Romero, France Leturcq, Pascal Laforêt, Thierry Maisonobe, Rim Amouri, Hafedh Haddad, [......], Ariane Herson, Yves Allenbach, François M Lemoine, David Klatzmann, H Lee Sweeney, Richard C Mulligan, Bruno Eymard, Didier Caizergues, Thomas Voït, Olivier Benveniste
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  ABSTRACT: γ-Sarcoglycanopathy or limb girdle muscular dystrophy type 2C is an untreatable disease caused by autosomal recessively inherited mutations of the γ-sarcoglycan gene. Nine non-ambulatory patients (two males, seven females, mean age 27 years; range 16-38 years) with del525T homozygous mutation of the γ-sarcoglycan gene and no γ-sarcoglycan immunostaining on muscle biopsy were divided into three equal groups to receive three escalating doses of an adeno-associated virus serotype 1 vector expressing the human γ-sarcoglycan gene under the control of the desmin promoter, by local injection into the extensor carpi radialis muscle. The first group received a single injection of 3 × 10(9) viral genomes in 100 µl, the second group received a single injection of 1.5 × 10(10) viral genomes in 100 µl, and the third group received three simultaneous 100-µl injections at the same site, delivering a total dose of 4.5 × 10(10) viral genomes. No serious adverse effects occurred during 6 months of follow-up. All nine patients became adeno-associated virus serotype 1 seropositive and one developed a cytotoxic response to the adeno-associated virus serotype 1 capsid. Thirty days later, immunohistochemical analysis of injected-muscle biopsy specimens showed γ-sarcoglycan expression in all three patients who received the highest dose (4.7-10.5% positively stained fibres), while real-time polymerase chain reaction detected γ-sarcoglycan messenger RNA. In one patient, γ-sarcoglycan protein was detected by western blot. For two other patients who received the low and intermediate doses, discrete levels of γ-sarcoglycan expression (<1% positively stained fibres) were also detectable. Expression of γ-sarcoglycan protein can be induced in patients with limb girdle muscular dystrophy type 2C by adeno-associated virus serotype 1 gene transfer, with no serious adverse effects.
  Brain 02/2012; 135(Pt 2):483-92. · 9.46 Impact Factor
• Article: Eosinophilic fasciitis (Shulman disease): new insights into the therapeutic management from a series of 34 patients.

  David Lebeaux, Camille Francès, Stéphane Barete, Bertrand Wechsler, Odile Dubourg, Jérôme Renoux, Thierry Maisonobe, Olivier Benveniste, Marc Gatfossé, Pierre Bourgeois, Zahir Amoura, Patrice Cacoub, Jean-Charles Piette, Damien Sène
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  ABSTRACT: To analyse therapeutic management of eosinophilic fasciitis (EF). We reviewed 34 adult patients with biopsy-proven EF. Analyses focused on the therapeutic management, including treatment modalities, responses and associated or predictive factors. Thirty-four patients were included with a diagnosis age of 53 (15) years. They were featured by cutaneous manifestations (88%) including morphoea (41%), myalgia (86%) and hypereosinophilia (85%). Thirty-two patients (94%) were eligible for treatment evaluation and all received CSs as a first-line therapy. Fifteen patients (47%) received methylprednisolone pulses (MPPs) at treatment initiation and 14 patients (44%) received an immunosuppressive drug (ISD), usually MTX (86%), as a second-line therapy. Complete remission was achieved for 69% of patients, remission with disability 19% and failure 12%. A poor outcome was associated with a diagnosis time delay of >6 months [odds ratio (OR) = 14.7] and the lack of MPPs (OR = 12.9). Our study reports new insights into the therapeutic management of EF: (i) CS treatment remains the standard therapy for EF, taken alone or in association with an ISD; (ii) MPPs at initiation of treatment are associated with a better outcome and a lower need of ISD use; (iii) an ISD, usually MTX, might be useful as a second-line therapy, mainly in patients with morphoea-like lesions. Naturally, these practical conclusions should be confirmed by a prospective and multicentre study.
  Rheumatology (Oxford, England) 11/2011; 51(3):557-61. · 4.24 Impact Factor
• Article: Long-term observational study of sporadic inclusion body myositis.

  Olivier Benveniste, Marguerite Guiguet, Jane Freebody, Odile Dubourg, Waney Squier, Thierry Maisonobe, Tanya Stojkovic, Maria Isabel Leite, Yves Allenbach, Serge Herson, Stefen Brady, Bruno Eymard, David Hilton-Jones
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  ABSTRACT: We describe a long-term observational study of a large cohort of patients with sporadic inclusion body myositis and propose a sporadic inclusion body myositis weakness composite index that is easy to perform during a clinic. Data collection from two groups of patients (Paris and Oxford) was completed either during a clinic visit (52%), or by extraction from previous medical records (48%). One hundred and thirty-six patients [57% males, 61 (interquartile range 55-69) years at onset] were included. At the last visit all patients had muscle weakness (proximal British Medical Research Council scale <3/5 in 48%, distal British Medical Research Council scale <3/5 in 40%, swallowing problems in 46%). During their follow-up, 75% of patients had significant walking difficulties and 37% used a wheelchair (after a median duration from onset of 14 years). The sporadic inclusion body myositis weakness composite index, which correlated with grip strength (correlation coefficient: 0.47; P < 0.001) and Rivermead Mobility Index (correlation coefficient: 0.85; P < 0.001), decreased significantly with disease duration (correlation coefficient: -0.47; P < 0.001). The risk of death was only influenced by older age at onset of first symptoms. Seventy-one (52%) patients received immunosuppressive treatments [prednisone in 91.5%, associated (in 64.8%) with other immunomodulatory drugs (intravenous immunoglobulins, methotrexate or azathioprine) for a median duration of 40.8 months]. At the last assessment, patients who had been treated were more severely affected on disability scales (Walton P = 0.007, Rivermead Mobility Index P = 0.004) and on the sporadic inclusion body myositis weakness composite index (P = 0.04). The first stage of disease progression towards handicap for walking was more rapid among patients receiving immunosuppressive treatments (hazard ratio = 2.0, P = 0.002). This study confirms that sporadic inclusion body myositis is slowly progressive but not lethal and that immunosuppressive treatments do not ameliorate its natural course, thus confirming findings from smaller studies. Furthermore, our findings suggest that immunosuppressant drug therapy could have modestly exacerbated progression of disability. The sporadic inclusion body myositis weakness composite index might be a valuable outcome measure for future clinical trials, but requires further assessment and validation.
  Brain 11/2011; 134(Pt 11):3176-84. · 9.46 Impact Factor
• Source

  Available from: cnrs.fr

  Article: Distal muscle involvement in granulomatous myositis can mimic inclusion body myositis.

  Sandrine Larue, Thierry Maisonobe, Olivier Benveniste, Catherine Chapelon-Abric, Olivier Lidove, Thomas Papo, Bruno Eymard, Odile Dubourg
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  ABSTRACT: The authors report on four patients aged over 50 with chronic myopathy suggestive of sporadic inclusion body myositis. They present progressive and selective weakness of the quadriceps femoris muscles. Asymmetrical and selective atrophy of the forearm muscles were noted in all, with more severe involvement of the flexors than the extensors. Biopsy revealed granulomatous myositis. Histological features of sporadic inclusion body myositis were lacking. Evidence for systemic sarcoidosis was found in one patient. Corticosteroid treatment was associated with a partial but significant improvement in two patients. Granulomatous myositis may mimic inclusion body myositis and may be steroid-responsive.
  Journal of neurology, neurosurgery, and psychiatry 06/2011; 82(6):674-7. · 4.87 Impact Factor
• Source

  Available from: Sylvie Delanian

  Article: Late onset radiation-induced camptocormia.

  Dimitri Psimaras, Thierry Maisonobe, Sylvie Delanian, Delphine Leclercq, Timothée Lenglet, Loïc Feuvret, Damien Ricard, Khê Hoang-Xuan, Pierre-François Pradat
  Journal of Neurology 03/2011; 258(9):1723-5. · 3.47 Impact Factor
• Article: Mononeuropathy multiplex associated with acute parvovirus B19 infection: characteristics, treatment and outcome.

  Timothée Lenglet, Julien Haroche, Aurélie Schnuriger, Thierry Maisonobe, Karine Viala, Yanne Michel, Farhat Chelbi, David Grabli, Paul Seror, Antoine Garbarg-Chenon, Zahir Amoura, Pierre Bouche
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  ABSTRACT: To describe the characteristics of peripheral neuropathy related to acute parvovirus B19 (B19V) infection. We reviewed clinical, electrophysiological and histological data of three patients with peripheral neuropathy and positive B19V detection (IgG, IgM and PCR) compatible with acute infection. The neuropathy fulfilled criteria for mononeuropathy multiplex (MM). It could be preceded by or concurrent with a limited purpuric eruption, but systemic manifestations were absent. The first neurological symptoms were always sensory and localized in a hand. Neuropathy was initially limited to a restricted sensory part of a nerve trunk territory. The course was subacute with successive and asymmetric injury of the limb and cranial nerves. Electromyographic study confirmed the diagnosis of MM with multifocal asymmetric sensory and motor axonal loss in two patients, whereas the neuropathy was purely sensory and limited to two nerves in the other patient. Nerve biopsies showed no evidence of necrotizing vasculitis but, in one patient, revealed a lymphocytic perivascular infiltrate evocative of hypersensitivity vasculitis secondary to an infectious agent. Intravenous immunoglobulin (IVIg) was systematically administered. Long-term outcome was good but with incomplete sensory recovery and, for one patient, persistence of a functional disability. B19 V infection should be considered in the etiological assessment of MM, especially in the event of a progressive sensory disorder in the hands and a concomitant history of rash. IVIg may be an effective treatment for this inflammatory disorder.
  Journal of Neurology 02/2011; 258(7):1321-6. · 3.47 Impact Factor
• Article: Peripheral neuropathies associated with primary Sjögren syndrome: immunologic profiles of nonataxic sensory neuropathy and sensorimotor neuropathy.

  Damien Sène, Moez Jallouli, Jean-Pascal Lefaucheur, David Saadoun, Nathalie Costedoat-Chalumeau, Thierry Maisonobe, Marie-Claude Diemert, Lucile Musset, Julien Haroche, Jean-Charles Piette, Zahir Amoura, Patrice Cacoub
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  ABSTRACT: We conducted this study to characterize the relationship between primary Sjögren syndrome (pSS)-associated peripheral neuropathy (PN) and markers of B-cell monoclonal proliferation and chronic activation. The cohort included 120 consecutive patients presenting with definite pSS according to the American-European Consensus Group criteria. Serum markers of chronic B-cell activation included autoantibodies and hypergammaglobulinemia. Markers of monoclonal B-cell proliferation included mixed cryoglobulin, monoclonal gammopathy, abnormal κ/λ free light chain (FLC) ratio, and B-cell non-Hodgkin lymphoma (B-NHL). Definite PN was present in 30 patients (25%) including 7 patients (23%) with sensorimotor neuropathy, 3 patients (10%) with ataxic sensory neuropathy, and 20 patients (67%) with nonataxic sensory neuropathy. Patients with a sensorimotor neuropathy differed from those without PN by higher rates of monoclonal B-cell proliferation markers, that is, mixed cryoglobulin (57% vs. 11%; p = 0.008), monoclonal gammopathy (71% vs. 17%; p = 0.004), higher FLC ratio (2.7 ± 1.5 vs. 1.7 ± 1.8; p = 0.024), and B-NHL (57% vs. 3%; p < 0.001). Patients with nonataxic sensory neuropathy were characterized by a higher age (57.5 ± 10.7 vs. 48.7 ± 14.3 years; p = 0.007), more frequent central nervous system (CNS) involvement (15% vs. 2%; p = 0.04) and a lower prevalence of chronic B-cell activation serum markers, that is, antinuclear antibodies (ANA) (60% vs. 90%; p = 0.003), anti-SSA (Ro) (40% vs. 72%; p = 0.009), anti-SSB (La) (15% vs. 41%; p = 0.039), rheumatoid factor (37% vs. 67%; p = 0.02), and hypergammaglobulinemia (35% vs. 64%; p = 0.023). In multivariate analysis, sensorimotor neuropathy was associated with the presence of B-NHL (odds ratio [OR], 39.0; p < 0.001), whereas nonataxic sensory neuropathy was associated with the presence of CNS involvement (OR, 17.0; p = 0.025) and ANA (OR, 0.07; p < 0.001). In conclusion, we found that up to 25% of pSS patients presented with PN, predominantly sensory neuropathy. Distinctive immunologic profiles were found according to the type of SS-associated neuropathy: nonataxic sensory neuropathy was marked by a low prevalence of B-cell activation markers, and sensorimotor neuropathy was marked by a high prevalence of B-cell monoclonal proliferation markers.
  Medicine 02/2011; 90(2):133-8. · 4.35 Impact Factor
• Source

  Available from: Jean-Jacques Hauw

  Article: Nodes of ranvier and paranodes in chronic acquired neuropathies.

  Carmen Cifuentes-Diaz, Odile Dubourg, Theano Irinopoulou, Marc Vigny, Sylvie Lachkar, Laurence Decker, Patrick Charnay, Natalia Denisenko, Thierry Maisonobe, Jean-Marc Léger, Karine Viala, Jean-Jacques Hauw, Jean-Antoine Girault
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  ABSTRACT: Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating polyneuropathies (CIDP) and chronic idiopathic axonal polyneuropathies (CIAP). The diagnosis can be very difficult, although it has important therapeutic implications since CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies. Longitudinal sections of superficial peroneal nerves were obtained from biopsy material from 12 patients with CIDP and 10 patients with CIAP and studied by immunofluorescence and in some cases electron microscopy. Electron microscopy revealed multiple alterations in the nodal and paranodal regions which predominated in Schwann cells in CIDP and in axons in CIAP. In CIDP paranodin/Caspr immunofluorescence was more widespread than in control nerves, extending along the axon in internodes where it appeared intense. Nodal channels Nav and KCNQ2 were less altered but were also detected in the internodes. In CIAP paranodes, paranodin labeling was irregular and/or decreased. To test the consequences of acquired primary Schwann cells alteration on axonal proteins, we used a mouse model based on induced deletion of the transcription factor Krox-20 gene. In the demyelinated sciatic nerves of these mice we observed alterations similar to those found in CIDP by immunofluorescence, and immunoblotting demonstrated increased levels of paranodin. Finally we examined whether the alterations in paranodin immunoreactivity could have a diagnosis value. In a sample of 16 biopsies, the study of paranodin immunofluorescence by blind evaluators led to correct diagnosis in 70 ± 4% of the cases. This study characterizes for the first time the abnormalities of nodes of Ranvier in CIAP and CIDP, and the altered expression and distribution of nodal and paranodal proteins. Marked differences were observed between CIDP and CIAP and the alterations in paranodin immunofluorescence may be an interesting tool for their differential diagnosis.
  PLoS ONE 01/2011; 6(1):e14533. · 4.09 Impact Factor
• Article: A novel MYH7 mutation occurring independently in French and Norwegian Laing distal myopathy families and de novo in one Finnish patient.

  Odile Dubourg, Thierry Maisonobe, Anthony Behin, Tiina Suominen, Olayinka Raheem, Sini Penttilä, Matt Parton, Bruno Eymard, Arve Dahl, Bjarne Udd
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  ABSTRACT: Laing early-onset distal myopathy is a rare autosomal dominant myopathy and caused by mutations in the MYH7 gene, encoding the slow beta myosin heavy chain. We report the first molecularly verified Laing distal myopathy in a French family caused by a novel p.Glu1508del mutation in the MYH7 gene. Interestingly, we identified the identical mutation in an unrelated Norwegian family and, as a de novo mutation, in one sporadic Finnish patient. Described in detail are the clinical and electrophysiological characteristics of 5 patients from the French family. The phenotype in the Finnish patient and the Norwegian patients is largely similar. This mutation causes a benign myopathy within the range of previously reported Laing myopathy phenotype variations. Onset of weakness in the tibialis anterior (TA) muscles occurred in early childhood in all patients. Finger extensor and neck flexor weakness together with Achilles tendon retractions were other frequent findings. The independent recurrence of the identical mutation without any founder background may reflect a mutational susceptibility of this residue, in accordance with some other MYH7 mutations previously reported. De novo mutations seem to be frequent in Laing distal myopathy. This is of clinical importance since a dominant family history is missing, which may confuse differential diagnostic efforts.
  Journal of Neurology 01/2011; 258(6):1157-63. · 3.47 Impact Factor
• Article: Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome.

  Benjamin Terrier, Ivan Bièche, Thierry Maisonobe, Ingrid Laurendeau, Michèlle Rosenzwajg, Jean-Emmanuel Kahn, Marie-Claude Diemert, Lucile Musset, Michel Vidaud, Damien Sène, Nathalie Costedoat-Chalumeau, Du Le Thi-Huong, Zahir Amoura, David Klatzmann, Patrice Cacoub, David Saadoun
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  ABSTRACT: Churg-Strauss syndrome (CSS) is characterized by systemic vasculitis and blood and tissue eosinophilia. Blood eosinophilia correlates with disease activity, and activated T cells from CSS patients are predominantly T helper 2 (Th2). Interleukin (IL)-25 has been shown to link innate and adaptive immunity by enhancing Th2 cytokine production. We sought to determine the involvement of IL-25 and its receptor IL-17RB in the pathogenesis of CSS. We found increased levels of IL-25 in the serum of active CSS patients (952 ± 697 vs 75 ± 49 pg/mL in inactive patients and 47 ± 6 pg/mL in healthy donors). IL-25 was correlated with disease activity and eosinophil level. Eosinophils were the main source of IL-25, whereas activated CD4(+) memory T cells were the IL-17RB-expressing cells in CSS. IL-25 enhanced the production of IL-4, IL-5, and IL-13 by activated peripheral blood mononuclear cells. IL-25 and IL-17RB were observed within the vasculitic lesions of patients with CSS, and IL-17RB colocalized with T cells. Increased expression of IL-17RB, tumor necrosis factor receptor-associated factor 6, and JunB in vasculitic lesions of CSS underscored the IL-25-mediated activation, whereas up-regulation of GATA3 and IL-10 supported Th2 differentiation. Our findings suggest that eosinophils, through the production of IL-25, exert a critical role in promoting Th2 responses in target tissues of CSS.
  Blood 11/2010; 116(22):4523-31. · 9.90 Impact Factor
• Article: Systemic vasculitis in patients with hepatitis C virus infection with and without detectable mixed cryoglobulinemia.

  Benjamin Terrier, Damien Sène, Agnès Dechartres, David Saadoun, Nicolas Ortonne, Philippe Rouvier, Lucile Musset, Matthieu Resche Rigon, Thierry Maisonobe, Patrice Cacoub
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  ABSTRACT: to describe hepatitis C virus (HCV)-related systemic vasculitis in patients without detectable mixed cryoglobulinemia (MC) and to compare them to typical cases of HCV-MC vasculitis. twelve HCV RNA+ patients with histologically proven vasculitis in the absence of detectable MC (cases) were retrospectively compared with 48 HCV RNA+ patients with MC vasculitis (controls). Each case was matched with 4 controls for age and sex. the main epidemiological and virologic features were similar between cases and controls. No clinical difference was found, except for lower rates of arthralgias (33% vs 71%; p = 0.02) and purpura (50% vs 83%; p = 0.03) in cases. Cases showed higher mean serum C3 (1.17 ± 0.21 vs 0.93 ± 0.23 g/l; p = 0.01) and median C4 levels (0.25 vs 0.04 g/l; p < 0.001), lower median serum IgM levels (0.6 vs 1.9 g/l; p < 0.001), and lower rates of rheumatoid factor positivity (8% vs 82%; p < 0.001) than controls. The main histologic features were similar between cases and controls. Immunofluorescence analysis of skin biopsy from 1 case revealed perivascular deposits of C3 and IgA. After treatment, overall clinical response of vasculitis (75% vs 83%) and sustained virological response (40% vs 64%; p = 0.3) were similar between cases and controls, except for higher complete clinical response (42% vs 73%; p = 0.05) in controls. HCV-related systemic vasculitis may occur in the absence of detectable MC. Our findings suggest that such vasculitis probably results from immune complex-mediated mechanisms, and that the therapeutic management of such vasculitis should be similar to that of HCV-MC vasculitis.
  The Journal of Rheumatology 10/2010; 38(1):104-10. · 3.69 Impact Factor
• Article: A current view of the diagnosis, clinical variants, response to treatment and prognosis of chronic inflammatory demyelinating polyradiculoneuropathy.

  Karine Viala, Thierry Maisonobe, Tanya Stojkovic, Régine Koutlidis, Xavier Ayrignac, Lucile Musset, Emmanuel Fournier, Jean-Marc Léger, Pierre Bouche
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  ABSTRACT: We retrospectively analyzed 146 patients fulfilling the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to (1) evaluate the relevance of these criteria, (2) assess the frequency of CIDP variants, and (3) determine the response to treatment and the prognosis. We found that 75% of these patients fulfilled the main EFNS/PNS clinical and electrophysiological criteria (type I). The remaining patients were diagnosed using laboratory tools as supportive criteria. The common form of CIDP represented 51% of patients. We observed a high frequency of the sensory variant (35% of patients) and the rapid onset form (18%). A positive response to treatment was observed in 87% of patients, with a similar efficacy of prednisone and IVIg. However, in the long term, 40% of treated patients remained dependent on treatment. The IVIg dependency rate was higher than the prednisone or plasma exchange dependency rate (55%, 18%, and 23%, respectively; p = 0.0054). Severe handicap was observed in 24% of patients.
  Journal of the Peripheral Nervous System 03/2010; 15(1):50-6. · 2.80 Impact Factor
• Source

  Available from: Sylvie Delanian

  Article: Significant clinical improvement in radiation-induced lumbosacral polyradiculopathy by a treatment combining pentoxifylline, tocopherol, and clodronate (Pentoclo).

  Sylvie Delanian, Jean-Louis Lefaix, Thierry Maisonobe, François Salachas, Pierre-François Pradat
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  ABSTRACT: Radiation-induced (RI) peripheral neuropathy is a rare and severe delayed complication of radiotherapy that is spontaneously irreversible, with no standard of treatment. We previously developed a successful antioxidant treatment in RI fibrosis and necrosis. Two patients with progressive worsening RI lumbosacral polyradiculopathy experienced over several years a significant clinical improvement in their neurological sensorimotor symptoms with long-term pentoxifylline-tocopherol-clodronate treatment, and good safety.
  Journal of the Neurological Sciences 10/2008; 275(1-2):164-6. · 2.35 Impact Factor
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  Available from: Sylvie Delanian

  Article: Postradiation lumbosacral radiculopathy with spinal root cavernomas mimicking carcinomatous meningitis.

  François Ducray, Rémy Guillevin, Dimitri Psimaras, Marc Sanson, Karima Mokhtari, Sylvie Delanian, Soledad Navarro, Thierry Maisonobe, Philippe Cornu, Khê Hoang-Xuan, Jean-Yves Delattre, Pierre-François Pradat
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  ABSTRACT: Lumbosacral radiculopathy is a rare complication of radiotherapy and may be challenging to differentiate from diagnosis of a tumor recurrence. We reviewed the records of three patients with a past history of cancer and radiotherapy who were referred for suspicion of carcinomatous meningitis on lumbar MRI, but whose final diagnosis was radiation-induced lumbosacral radiculopathy. The three patients developed a progressive lumbosacral radiculopathy at 20, 13, and 47 years after lumbar radiotherapy delivered for renal cancer, Hodgkin's disease, and a seminoma, respectively. MRI showed a diffuse, nodular enhancement of the cauda equina nerve roots on T1 sequences, suggestive of leptomeningeal metastasis. A slowly progressive clinical course over several years and negative cerebrospinal fluid cytologic analysis ruled out the diagnosis of carcinomatous meningitis. Because of the radiologic findings, a biopsy was performed in two patients. In the first, a biopsy limited to the arachnoid excluded a malignant infiltration. In the second, a biopsy of the enhancing lesions demonstrated spinal root cavernomas. These observations, together with three recent case reports in the literature, delineate a syndrome of "radiationinduced lumbosacral radiculopathy with multiple spinal root cavernomas" that mimics carcinomatous meningitis on MRI. Its diagnosis is important in order to avoid inappropriate treatment and useless or dangerous spinal root biopsies.
  Neuro-Oncology 09/2008; 10(6):1035-9. · 5.72 Impact Factor
• Article: Lewis-Sumner syndrome and Tangier disease.

  Marie Théaudin, Philippe Couvert, Emmanuel Fournier, Daniel Bouige, Eric Bruckert, Paul Perrotte, Yvan Vaschalde, Thierry Maisonobe, Dominique Bonnefont-Rousselot, Alain Carrié, Nadine Le Forestier
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  ABSTRACT: To report unusual electrophysiologic data in a patient with Tangier disease in an effort to better understand the pathophysiologic features of the peripheral nerve lesions in this disease. Case report. A 15-year-old girl had subacute onset of asymmetric neuropathy with persistent conduction block, resembling Lewis-Sumner syndrome. Electrophysiologic data in Tangier disease. After initially unsuccessful treatment with intravenously administered immunoglobulins, the finding of an abnormal lipid profile led to the diagnosis of Tangier disease due to the R587W mutation in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1) (OMIM 9q22-q31). Conduction block, which is the electrophysiologic hallmark of focal demyelination, can be present in Tangier disease. It could be induced by focal nerve ischemia or by preferential lipid deposition in the paranodal regions of myelinated Schwann cells. The presence of a conduction block in Tangier disease may lead to a misdiagnosis of dysimmune neuropathy.
  Archives of neurology 08/2008; 65(7):968-70. · 6.31 Impact Factor