Publications by authors named "Céline Tard"

42 Publications

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy-analysis of registry data.

Eur Heart J 2021 Mar 22. Epub 2021 Mar 22.

APHP, Cochin Hospital, Cardiology Department, FILNEMUS, Paris-Descartes, Sorbonne Paris Cité University, Paris, France.

Aims: To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD).

Methods And Results: We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34-0.72] and 0.47 (95% CI 0.31-0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17-0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04-0.62). All other sensitivity analyses yielded similar results.

Conclusion: Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab054DOI Listing
March 2021

Impact of Coronavirus Disease 2019 in a French Cohort of Myasthenia Gravis.

Neurology 2021 Feb 10. Epub 2021 Feb 10.

Referral Center for Neuromuscular Diseases and ALS, Timone University Hospital, Aix-Marseille University, Marseille, France.

Objective: To describe the clinical characteristics and outcomes of COVID-19 among patients with MG and identify factors associated with COVID-19 severity in MG patients.

Methods: The CO-MY-COVID registry was a multicenter, retrospective, observational cohort study conducted in neuromuscular referral centers and general hospitals of the FILNEMUS network (between March 1, 2020, and June 8, 2020), including MG patients with a confirmed or highly-suspected diagnosis of COVID-19. COVID-19 was diagnosed based on a polymerase chain reaction (PCR) test from a nasopharyngeal swab and/or SARS-CoV-2 serology, thoracic computed tomography (CT-scan), or typical symptoms. The main outcome was COVID-19 severity based on location of treatment/management (home, hospitalized in a medical unit, or in an intensive care unit). We collected information on demographic variables, general history, and risk factors for severe COVID-19. Multivariate ordinal regression models were used to identify factors associated with severe COVID-19 outcomes.

Results: Among 3,558 MG patients registered in the French database for rare disorders, 34 (0.96%) had COVID-19. The mean age at COVID-19 onset was 55.0 ±19.9 years (mean MG duration: 8.5 ± 8.5 years). By the end of the study period, 28 patients recovered from COVID-19, 1 remained affected, and 5 died. Only high Myasthenia Gravis Foundation of America (MGFA) class (≥IV) before COVID-19 was associated with severe COVID-19 (p=0.004); factors that were not associated included gender, MG duration, and medium MGFA classes (≤IIIb). The type of MG treatment had no independent effect on COVID-19 severity.

Conclusions: This registry-based cohort study shows that COVID-19 had a limited effect on most patients, and immunosuppressive medications and corticosteroids used for MG management are not risk factors for poorer outcomes. However, the risk of severe COVID-19 is elevated in patients with high MGFA classes [odds ratio: 102.6 (4.4; 2,371.9)]. These results are important for establishing evidence-based guidelines for the management of MG patients during the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011669DOI Listing
February 2021

Do kinematic gait parameters help to discriminate between fallers and non-fallers with Parkinson's disease?

Clin Neurophysiol 2021 Feb 19;132(2):536-541. Epub 2020 Dec 19.

Univ. Lille, Inserm, U1172 - Lille Neuroscience and Cognition, F-59000 Lille, France; Neurology and Movement Disorders Department, Lille University Medical Center, F-59000 Lille, France; Lille Center of Excellence for Neurodegenerative Diseases, LiCEND, France.

Objective: Although a number of clinical factors have been linked to falls in Parkinson's disease (PD), the diagnostic value of gait parameters remains subject to debate. The objective of this retrospective study was to determine to what extent the combination of gait parameters with clinical characteristics can distinguish between fallers and non-fallers.

Methods: Using a video motion system, we recorded gait in 174 patients with PD. The patients' clinical characteristics (including motor status, cognitive status, disease duration, dopaminergic treatment and any history of falls or freezing of gait) were noted. The considered kinematic gait parameters included indices of gait bradykinesia and hypokinesia, asymmetry, variability, and foot clearance. After a parameters selection using an ANCOVA analysis, support vector machine algorithm was used to build classification models for distinguishing between fallers and non-fallers. Two models were built, the first included clinical data only while the second incorporated the selected gait parameters.

Results: The "clinical-only" model had an accuracy of 94% for distinguishing between fallers and non-fallers. The model incorporating additional gait parameters including stride time and foot clearance performed even better, with an accuracy of up to 97%.

Conclusion: Although fallers differed significantly from non-fallers with regard to disease duration, motor impairment or dopaminergic treatment, the addition of gait parameters such as foot clearance or stride time to clinical variables increased the model's discriminant power.

Significance: This predictive model now needs to be validated in prospective cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.11.027DOI Listing
February 2021

Erratum to 'Can dual-task paradigms predict falls better than single task? - A systematic literature review' [Neurophysiol Clin 50 (2020) 401-40].

Neurophysiol Clin 2020 Dec 23. Epub 2020 Dec 23.

Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Department of Clinical Neurophysiology, F-59000 Lille, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neucli.2020.12.004DOI Listing
December 2020

Can dual-task paradigms predict Falls better than single task? - A systematic literature review.

Neurophysiol Clin 2020 Nov 8;50(6):401-440. Epub 2020 Nov 8.

Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Department of Clinical Neurophysiology, F-59000 Lille, France. Electronic address:

With about one third of adults aged 65 years and older being reported worldwide to fall each year, and an even higher prevalence with advancing age, aged-related falls and the associated disabilities and mortality are a major public health concern. In this context, identification of fall risk in healthy older adults is a key component of fall prevention. Since dual-task outcomes rely on the interaction between cognition and motor control, some studies have demonstrated the role of dual-task walking performance or costs in predicting future fallers. However, based on previous reviews on the topic, (1) discriminative and (2) predictive powers of dual tasks involving gait and a concurrent task are still a matter of debate, as is (3) their superiority over single tasks in terms of fall-risk prediction. Moreover, less attention has been paid to dual tasks involving postural control and transfers (such as gait initiation and turns) as motor tasks. In the present paper, we therefore systematically reviewed recent literature over the last 7 years in order to answer the three above mentioned questions regarding the future of lab-based dual tasks (involving posture, gait initiation, gait and turning) as easily applicable tests for identifying healthy older adult fallers. Despite great heterogeneity among included studies, we emphasized, among other things, the promising added value of dual tasks including turns and other transfers, such as in the Timed Up and Go test, for prediction of falls. Further investigation of these is thus warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neucli.2020.10.008DOI Listing
November 2020

CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell-targeted therapies.

Blood 2020 11;136(21):2428-2436

Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, Assitance Publique des Hôpitaux de Paris (AP1HP), Paris, France.

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020007092DOI Listing
November 2020

Motor unit number index as an individual biomarker: Reference limits of intra-individual variability over time in healthy subjects.

Clin Neurophysiol 2020 Sep 9;131(9):2209-2215. Epub 2020 Jul 9.

Referral Centre for Neuromuscular Diseases and ALS, La Timone Hospital, Marseille, France.

Objective: Motor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX.

Methods: In 11 different hospital centres, MUNIX was assessed twice, at least 3 months apart (range 90-360 days), in tibialis anterior (TA), abductor pollicis brevis (APB), abductor digiti minimi (ADM) and deltoid muscles in 118 healthy subjects. MUNIX sum score 2, 3 and 4 were respectively the sum of the MUNIX of the TA and ADM, of the TA, APB and ADM and of the TA, APB, ADM and deltoid muscles.

Results: The repeatability of the MUNIX was better for sum scores than for single muscle recordings. The variability of the MUNIX was independent of sex, age, interval between measurements and was lower for experienced than non-experienced operators. The 95th percentile of the coefficient of variability of the MUNIX sum score 2, 3 and 4 were respectively 22%, 18% and 15% for experienced operators.

Conclusions: The MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability.

Significance: A variation of the MUNIX sum score ≥20% can be interpreted as a significant change of muscle innervation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.06.019DOI Listing
September 2020

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera.

J Neurol 2020 Dec 16;267(12):3664-3672. Epub 2020 Jul 16.

Timone Neuroscience Institute, UMR CNRS 7289, Aix-Marseille University, 13005, Marseille, France.

Introduction: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP.

Methods: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department.

Results: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies).

Conclusions: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-020-10041-zDOI Listing
December 2020

Long-term benefit of enzyme replacement therapy with alglucosidase alfa in adults with Pompe disease: Prospective analysis from the French Pompe Registry.

J Inherit Metab Dis 2020 11 27;43(6):1219-1231. Epub 2020 Jul 27.

Centre de référence des maladies neuromusculaires Nord-Est-Ile de France, Service de Neurologie, CHU Raymond Poincaré, AP-HP, Garches, France.

Despite a wide clinical spectrum, the adult form of Pompe disease is the most common one, and represents more than 90% of diagnosed patients in France. Since the marketing of enzyme replacement therapy (alglucosidase alfa, Myozyme), all reports to date in adults demonstrated an improvement of the walking distance, and a trend toward stabilization of respiratory function, but the majority of these studies were less than 5 years of duration. We report here the findings from 158 treated patients included in the French Pompe Registry, who underwent regular clinical assessments based on commonly used standardized tests (6-minute walking test, MFM scale, sitting vital capacity, MIP and MEP). For longitudinal analyses, the linear mixed effects models were used to assess trends in primary endpoints over time under ERT. A two-phase model better described the changes in distance traveled in the 6-minute walk test and MFM. 6MWT showed an initial significant increase (1.4% ± 0.5/year) followed by a progressive decline (-2.3%/year), with a cut-off point at 2.2 years. A similar pattern was observed in total MFM score (6.6% ± 2.3/year followed by a - 1.1%/year decline after 0.5 years). A single-phase decline with a slope of -0.9 ± 0.1%/year (P < .001) was observed for FVC, and MEP remained stable over the all duration of follow-up. This study provides further evidence that ERT improves walking abilities and likely stabilizes respiratory function in adult patients with Pompe disease, with a ceiling effect for the 6MWT in the first 3 years of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12272DOI Listing
November 2020

Electrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy associated with IgG4 antibodies targeting neurofascin 155 or contactin 1 glycoproteins.

Clin Neurophysiol 2020 04 6;131(4):921-927. Epub 2020 Feb 6.

Referral Centre for Neuromuscular Diseases and ALS, La Timone hospital, Marseille, France; Aix-Marseille University, Timone Neuroscience Institute, UMR CNRS 7289, 13005 Marseille, France. Electronic address:

Objective: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics.

Methods: The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies.

Results: All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve <24 m/s or motor velocity on ulnar nerve <26 m/s or motor distal latency on ulnar nerve >7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%.

Conclusions: Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier.

Significance: Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a "demyelinating" neuropathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.01.013DOI Listing
April 2020

A new paradigm to study the influence of attentional load on cortical activity for motor preparation of step initiation.

Exp Brain Res 2020 Mar 5;238(3):643-656. Epub 2020 Feb 5.

Univ. Lille, Inserm, Lille Neuroscience & Cognition, UMR-S1172, Degenerative and Vascular Cognitive Disorders, F-59000, Lille, France.

Motor programme for gait initiation can vary as a function of attentional resources. The objective of the present study was to determine whether alertness, orientation and executive control can modulate cortical activation during step initiation. The attention network test (ANT) was used to control the influence of different attentional components on kinetic characteristics of step initiation and the associated cortical activity. Thirty healthy adults performed ANT combined with step initiation. The step execution time (SET) and anticipatory postural adjustments (APAs) were recorded. Movement-related cortical potentials (MRCPs) and event-related spectral perturbations (ERSPs) after response emission were analysed according to the presence or absence of cueing or conflict resolution. Step reaction time and thus SET were significantly shorter with cueing, whereas APA duration and SET were longer during conflict resolution. Moreover, alertness was related to a higher rate of anticipated responses, and conflicting situations were associated with a greater amount of multiple APAs. Attentional load did not affect MRCPs but ERSPs: trials with a cue showed earlier posterior alpha and beta desynchronisations before APA onset. Furthermore, we found earlier, more pronounced and longer alpha- and beta-band desynchronisations over the sensorimotor cortex for trials with incongruent flankers. Our results showed that attention has an impact on step initiation. A specific pattern of response-locked ERSPs seems to mirror behavioural effects of attentional load on step initiation. This new paradigm combining ANT and step initiation is, therefore, promising to investigate the interaction between attention and gait initiation in pathological populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00221-020-05739-5DOI Listing
March 2020

A Rare and Treatable Cause of Medullar Claudication: Spinal Dural Arteriovenous Fistula.

Ochsner J 2019 ;19(4):397-400

Degenerative and Vascular Cognitive Disorders, U1171, University Lille, INSERM, Centre Hospitalier Universitaire de Lille, Lille, France.

Spinal dural arteriovenous fistula is a rare and underdiagnosed disorder. Because of the nonspecific clinical presentation of the condition, patients are often referred to different specialists, resulting in delayed diagnosis. A 76-year-old male presented with a 1-month history of gait trouble. His impairment was asymmetric, distally predominant, sensitive, and motor. Symptoms worsened with standing and walking. The patient also had sphincterial dysfunction. Classic spinal cord magnetic resonance imaging (MRI) showed an extended hypersignal indicating nonspecific myelopathy. Repeat spinal cord MRI that included a T2 spin echo sequence revealed abnormalities suggesting dural arteriovenous fistula. Medullar angiography confirmed the diagnosis, and endovascular treatment was successfully performed. Six months posttreatment, the patient reported resolution of his neurologic disabilities except for some residual paresthesia in his inferior limbs. Physicians should be aware of the specific abnormalities shown on spinal cord MRI that indicate dural arteriovenous fistula, as well as the criteria for performing medullar angiography, so that the condition can be diagnosed and treated in a timely manner. Early therapeutic treatment is the principal prognosis factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.31486/toj.18.0026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928661PMC
January 2019

Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

J Neurol 2020 Mar 14;267(3):703-712. Epub 2019 Nov 14.

AP-HP, Université Paris Saclay, CHU Bicêtre, Université Paris-Sud, INSERM 1195, Paris, France.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-019-09602-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035216PMC
March 2020

Graft-versus-host disease-related neuropathy: AMAN phenotype with improvement after plasmapheresis.

Acta Neurol Belg 2020 Jun 24;120(3):719-722. Epub 2019 Sep 24.

Service d'hématologie médicale, CHU de Lille, Lille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-019-01211-6DOI Listing
June 2020

Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation.

Hum Mutat 2020 01 15;41(1):17-37. Epub 2019 Sep 15.

Department of translational medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.

Calcium (Ca ) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca entry, storage, and release. Store-operated Ca entry (SOCE) is a major mechanism controlling extracellular Ca entry, and mainly relies on the accurate interplay between the Ca sensor STIM1 and the Ca channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23899DOI Listing
January 2020

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

Authors:
Karim Wahbi Rabah Ben Yaou Estelle Gandjbakhch Frédéric Anselme Thomas Gossios Neal K Lakdawala Caroline Stalens Frédéric Sacher Dominique Babuty Jean-Noel Trochu Ghassan Moubarak Kostantinos Savvatis Raphaël Porcher Pascal Laforêt Abdallah Fayssoil Eloi Marijon Tanya Stojkovic Anthony Béhin Sarah Leonard-Louis Guilhem Sole Fabien Labombarda Pascale Richard Corinne Metay Susana Quijano-Roy Ivana Dabaj Didier Klug Marie-Christine Vantyghem Philippe Chevalier Pierre Ambrosi Emmanuelle Salort Nicolas Sadoul Xavier Waintraub Khadija Chikhaoui Philippe Mabo Nicolas Combes Philippe Maury Jean-Marc Sellal Usha B Tedrow Jonathan M Kalman Jitendra Vohra Alexander F A Androulakis Katja Zeppenfeld Tina Thompson Christine Barnerias Henri-Marc Bécane Eric Bieth Franck Boccara Damien Bonnet Françoise Bouhour Stéphane Boulé Anne-Claire Brehin Françoise Chapon Pascal Cintas Jean-Marie Cuisset Jean-Marc Davy Annachiara De Sandre-Giovannoli Florence Demurger Isabelle Desguerre Klaus Dieterich Julien Durigneux Andoni Echaniz-Laguna Romain Eschalier Ana Ferreiro Xavier Ferrer Christine Francannet Mélanie Fradin Bénédicte Gaborit Arnaud Gay Albert Hagège Arnaud Isapof Isabelle Jeru Raul Juntas Morales Emmanuelle Lagrue Nicolas Lamblin Olivier Lascols Vincent Laugel Arnaud Lazarus France Leturcq Nicolas Levy Armelle Magot Véronique Manel Raphaël Martins Michèle Mayer Sandra Mercier Christophe Meune Maud Michaud Marie-Christine Minot-Myhié Antoine Muchir Aleksandra Nadaj-Pakleza Yann Péréon Philippe Petiot Florence Petit Julien Praline Anne Rollin Pascal Sabouraud Catherine Sarret Stéphane Schaeffer Frederic Taithe Céline Tard Vincent Tiffreau Annick Toutain Camille Vatier Ulrike Walther-Louvier Bruno Eymard Philippe Charron Corinne Vigouroux Gisèle Bonne Saurabh Kumar Perry Elliott Denis Duboc

Circulation 2019 07 3;140(4):293-302. Epub 2019 Jun 3.

APHP, Cochin Hospital, Cardiology Department, FILNEMUS, Centre de Référence de Pathologie Neuromusculaire Nord/Est/Ile de France, Paris-Descartes, Sorbonne Paris Cité University (K.W., D.D.).

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation.

Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range].

Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach.

Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039410DOI Listing
July 2019

The interaction between cognition and motor control: A theoretical framework for dual-task interference effects on posture, gait initiation, gait and turning.

Neurophysiol Clin 2018 Dec 26;48(6):361-375. Epub 2018 Oct 26.

Inserm U1171, Degenerative and Vascular Cognitive Disorders, Lille University, 59000 Lille, France; Department of Clinical Neurophysiology, Lille University Medical Center, 59000 Lille, France. Electronic address:

Studies of dual-tasks (i.e. situations during which an individual performs two tasks simultaneously) and the subsequent inter-task interference have shown that locomotion and posture involves motor and cognitive components. Dual-tasks therefore constitute a promising avenue for improving the diagnosis, prevention and management of falls or cognitive impairment in populations at risk. However, tackling these major public health concerns with dual-task interventions requires a better understanding of the mechanisms underlying dual-task interference. In this context, we review (i) the main dual-task theories proposed to date and (ii) the factors that can influence dual-task interference effects in healthy young individuals and might therefore explain the current lack of consensus on the mechanisms of dual-tasks. We also consider cognitive-motor dual-tasks in which the motor task is a less frequently studied transition movement (such as gait initiation or turning), rather than only the often-studied gait and posture tasks. In general, the review focuses on the behavioral effects of dual-tasking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neucli.2018.10.003DOI Listing
December 2018

Motor Preparation of Step Initiation: Error-related Cortical Oscillations.

Neuroscience 2018 11 10;393:12-23. Epub 2018 Oct 10.

Univ. Lille, CHU Lille, INSERM, U1171 - Degenerative & Vascular Cognitive Disorders, F-59000 Lille, France; Lille Centre of Excellence for Neurodegenerative Diseases (LiCEND), F-59000 Lille, France.

Gait initiation can vary as a function of the available and engaged attentional resources. Conflict resolution can disrupt movement preparation and lead to "errors" in motor programming. These "errors" are physiologically useful by enabling us to adapt our motor behavior to situations with conflicting information. The objective of the present study was to analyze the patterns of cortical activation associated with motor programming errors and the corresponding error corrections. Incongruent flankers around a target arrow were used to trigger errors in anticipatory postural adjustments (APAs) prior to gait initiation; i.e. perturbed motor programming but normal execution. Thirty healthy adults performed a gait initiation task. The event-related potentials (ERPs) and event-related desynchronization (ERD) after target presentation were analyzed according to the presence or absence of an APA error. The ERP was similar in both conditions, except that the Ne and P300 peak latencies were longer for APA errors. Motor programming errors during gait initiation were characterized by longer, less intense low-beta-band ERD over the sensorimotor cortex and alpha ERS followed by stronger alpha ERD during errors. APA errors were associated with a specific alpha/beta oscillation profile over the sensorimotor cortex; these beta oscillations might be sensitive markers of non-conscious motor error and correction monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2018.09.046DOI Listing
November 2018

Author Correction: Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes.

Nat Immunol 2018 Sep;19(9):1035

INSERM U1016, Institut Cochin, Paris, France, and Université Paris Descartes, Paris, France.

In the version of this Article originally published, the asterisks indicating statistical significance were missing from Supplementary Figure 6; the file with the correct figure is now available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41590-017-0023-9DOI Listing
September 2018

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes.

Nat Immunol 2017 Dec 9;18(12):1321-1331. Epub 2017 Oct 9.

INSERM U1016, Institut Cochin, Paris, France, and Université Paris Descartes, Paris, France.

Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ni.3854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025738PMC
December 2017

Freezing during tapping tasks in patients with advanced Parkinson's disease and freezing of gait.

PLoS One 2017 8;12(9):e0181973. Epub 2017 Sep 8.

Univ. Lille, INSERM U1171 Degenerative & Vascular Cognitive Disorders, Lille, France.

Introduction: Parkinson's disease patients with freezing of gait also experience sudden motor blocks (freezing) during other repetitive motor tasks. We assessed the proportion of patients with advanced PD and freezing of gait who also displayed segmental "freezing" in tapping tasks.

Methods: Fifteen Parkinson's disease patients with freezing of gait were assessed. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers. Patients performed repetitive tapping movements (as described in the MDS-UPDRS task) with the hands or the feet in the presence or absence of a metronome set to 4 Hz. Movements were recorded with a video motion system. The primary endpoint was the occurrence of segmental freezing in these tapping tasks. The secondary endpoints were (i) the relationship between segmental episodic phenomena and FoG severity, and (ii) the reliability of the measurements.

Results: For the upper limbs, freezing was observed more frequently with a metronome (21% of trials) than without a metronome (5%). For the lower limbs, the incidence of freezing was higher than for the upper limbs, and was again observed more frequently in the presence of an auditory cue (47%) than in its absence (14%).

Conclusion: Although freezing of the lower limbs was easily assessed during an MDS-UPDRS task with a metronome, it was not correlated with the severity of freezing of gait (as evaluated during a standardized gait trajectory). Only this latter was a reliable measurement in patients with advanced Parkinson's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181973PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590736PMC
October 2017

Effect of enzyme replacement therapy with alglucosidase alfa (Myozyme®) in 12 patients with advanced late-onset Pompe disease.

Mol Genet Metab 2017 09 20;122(1-2):80-85. Epub 2017 Jun 20.

Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.

Background: The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease.

Methods: We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared.

Results: Twelve patients (7 males) were identified. Median age at symptom onset was 24years [IQR=15.5; 36.0]. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h [IQR=21.88; 24.00] (min 20; max 24). ERT was initiated at a median age of 52.5years [IQR=35.75; 66.50]. Median treatment duration was 55months [IQR=39.5; 81.0]. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m.

Conclusion: Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgme.2017.06.007DOI Listing
September 2017

Camptocormia and myalgia as the revealing symptoms of a drug-induced myopathy related to chronic orlistat intake: a case report.

Acta Neurol Belg 2018 Mar 16;118(1):115-118. Epub 2017 Mar 16.

Département de Neurologie, Hôpital Roger Salengro, Centre Hospitalier Régional Universitaire, Université de Lille 2, 1 Rue Emile Laine, 59037, Lille Cedex, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-017-0768-9DOI Listing
March 2018

Myogenic abnormalities in intensive care can hide an uncommon diagnosis.

Acta Neurol Belg 2017 09 7;117(3):789-790. Epub 2017 Feb 7.

Département de Neurologie, Hôpital Roger Salengro, Université de Lille, 1 rue Emile Laine, 59037, Lille Cedex, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-017-0756-0DOI Listing
September 2017

Attention modulation during motor preparation in Parkinsonian freezers: A time-frequency EEG study.

Clin Neurophysiol 2016 Dec 5;127(12):3506-3515. Epub 2016 Oct 5.

Université de Lille, Lille, France; Troubles cognitifs, dégénératifs et vasculaires, INSERM U1171, France; Service de Neurophysiologie clinique, CHRU de Lille, Lille, France.

Objective: To investigate the cortical integration of attentional stimuli during motor preparation in parkinsonian patients with freezing of gait (FoG, n=12) or without freezing of gait (n=13), and in aged-matched healthy controls (n=13). We hypothesized that interference between attention and action in freezers would be revealed by differences in cortical modulation during this dual task.

Methods: Attention during step preparation was modulated by means of an auditory oddball discrimination task. EEG oscillations in different frequency bands were measured for the attentional stimulus and the motor stimulus.

Results: Over the 500ms following the sound, low-frequency power increased in all three groups. This was followed by a power decrease in mid-range frequencies after both target and standard sounds in the healthy controls and in the non-FoG group. In contrast, EEG oscillations in the beta band were impaired in the FoG group, who notably failed to display event-related desynchronization after perceiving the sound.

Conclusions: An attentional stimulus was able to trigger event-related desynchronization before motor preparation in the non-FoG group but not in the FoG group.

Significance: In the FoG group, stimulus discrimination was maintained but the coupling between attention and motor preparation was impaired.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2016.09.014DOI Listing
December 2016

Are Upper-Body Axial Symptoms a Feature of Early Parkinson's Disease?

PLoS One 2016;11(9):e0162904. Epub 2016 Sep 21.

Department of Neurology and Movement Disorders, CHU, Lille, France.

Background: Axial disorders are considered to appear late in the course of Parkinson's disease (PD). The associated impact on quality of life (QoL) and survival and the lack of an effective treatment mean that understanding and treating axial disorders is a key challenge. However, upper-body axial disorders (namely dysarthria, swallowing and breathing disorders) have never been prospectively assessed in early-stage PD patients.

Objectives: To characterize upper-body axial symptoms and QoL in consecutive patients with early-stage PD.

Methods: We prospectively enrolled 66 consecutive patients with early-stage PD (less than 3 years of disease progression) and assessed dysarthria, dysphagia and respiratory function (relative to 36 controls) using both objective and patient-reported outcomes.

Results: The mean disease duration was 1.26 years and the mean UPDRS motor score was 19.4 out of 108. 74% of the patients presented slight dysarthria (primarily dysprosodia). Men appeared to be more severely affected (i.e. dysphonia). This dysfunction was strongly correlated with low swallowing speed (despite the absence of complaints about dysphagia), respiratory insufficiency and poor QoL. Videofluorography showed that oral-phase swallowing disorders affected 60% of the 31 tested patients and that pharyngeal-phase disorders affected 21%. 24% of the patients reported occasional dyspnea, which was correlated with anxiety in women but not in men. Marked diaphragmatic dysfunction was suspected in 42% of the patients (predominantly in men).

Conclusion: Upper body axial symptoms were frequent in men with early-stage PD, whereas women presented worst non-motor impairments. New assessment methods are required because currently available tools do not reliably detect these upper-body axial disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031440PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162904PLOS
September 2016

Freezing/festination during motor tasks in early-stage Parkinson's disease: A prospective study.

Mov Disord 2016 12 13;31(12):1837-1845. Epub 2016 Sep 13.

Université de Lille, INSERM U1171-Troubles cognitifs dégénératifs et vasculaires, Lille, France.

Background: Parkinsonian patients have a tendency to speed up during repetitive motor tasks (festination) and to experience sudden motor blocks (freezing). In this article, we prospectively studied the appearance and progression of these phenomena in 30 early-stage PD patients.

Methods: A total of 30 controls and early-stage PD patients were assessed in the "off-drug" condition at baseline and 2 years later. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers. Patients also performed diadochokinetic tasks with 3 different effectors (repetitive, antiphase movements for the hands and feet, and repetitive syllable production for the orofacial effector) at frequencies ranging from 1 to 7 Hz (in random order). The primary endpoint was the occurrence of freezing and festination.

Results: At baseline, freezing was observed in 6.5% of the trials in PD patients (43% of the patients) and 2.3% of the trials in controls, and festination was observed in 5.7% of the trials in patients (53% of the patients) and 0.8% of the trials in controls. These proportions were slightly higher in patients 2 years later. None of the patients presented freezing of gait at baseline, but 2 displayed this condition 2 years later. These phenomena occurred more frequently for the limb effectors than for the orofacial effector. Freezing and festination were associated with the akinetic-rigid subtype, although tremor-dominant patients displayed greater rhythm variability outside episodes.

Conclusion: Freezing and festination of the upper and lower limbs are observed soon after the diagnosis of PD and may be early biomarkers for disease progression. © 2016 International Parkinson and Movement Disorder Society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.26762DOI Listing
December 2016