John Vissing

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (228)1212.01 Total impact

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    ABSTRACT: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease. All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed. Thirty-two patients were included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation. This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression. © 2015 American Academy of Neurology.
    Neurology 04/2015; DOI:10.1212/WNL.0000000000001519 · 8.30 Impact Factor
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    ABSTRACT: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic myopathy. We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance in the patients on another day. Total fatty acid oxidation rates during exercise were higher in patients than controls, 32.1 (SE 1.2) vs 20.7 (SE 0.5; range 15.8-29.3) μmol/kg/min (p = 0.048), and oxidation of carbohydrates was lower in patients, 1.0 (SE 5.4) vs 38.4 (SE 8.0; range 23.0-77.1) μmol/kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients. Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation, and fructose ingestion improves exercise tolerance. Our results indicate that GSDIIIa should not only be viewed as a glycogenosis with fixed skeletal muscle weakness, but should also be considered among the glycogenoses presenting with exercise-related dynamic symptoms caused by muscular energy deficiency. This study provides Class IV evidence that ingestion of fructose improves exercise tolerance in patients with GSDIIIa. © 2015 American Academy of Neurology.
    Neurology 04/2015; DOI:10.1212/WNL.0000000000001518 · 8.30 Impact Factor
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    ABSTRACT: Background: Currently, there is no satisfactory treatment for McArdle disease. Sodium valproate is one of a group of drugs known as histone deacetylase inhibitors (HDACIs) that can affect gene expression by acetylating lysine residues, which in turn has a direct effect on chromatin. A recent clinical trial of the drug in McArdle sheep that were given sodium valproate showed the presence of phosphorylase positive muscle fibres. Aims: The aim of this pilot study is to determine the feasibility of performing a clinical trial of sodium valproate in people with McArdle disease. Methods: 15 subjects will receive sodium valproate modified release 20mg/kg/day (maximum dose 2.0g/day) administered orally once daily for six months. Outcome measurements include cycle ergometry (rating of perceived exertion, oxygen consumption and the respiratory quotient, serum lactate and ammonia levels, maximum heart rate and workload), the number of phosphorylase positive fibres on muscle biopsy pre and post treatment, maximum walking distance measured by the 12 minute walk test, forearm exercise test, blood laboratory parameters, quality of life questionnaire, symptom diary and side effect diary. Results: We expected an improvement in functional capacity in patients treated with sodium valproate in association with an increase in phosphorylase expression in muscle fibres. Conclusion: This pilot study might be the initial step in exploring a novel treatment option for patients with McArdle disease. Funder: Muscular Dystrophy Campaign
    Neuromuscular Disorders 03/2015; 25(S1):S32. · 3.13 Impact Factor
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    ABSTRACT: Background:Mitochondrial mutations are commonly reported in tumours, but it is unclear whether impaired mitochondrial function per se is a cause or consequence of cancer. To elucidate this, we examined the risk of cancer in a nationwide cohort of patients with mitochondrial dysfunction.Methods:We used nationwide results on genetic testing for mitochondrial disease and the Danish Civil Registration System, to construct a cohort of 311 patients with mitochondrial dysfunction. A total of 177 cohort members were identified from genetic testing and 134 genetically untested cohort members were matrilineal relatives to a cohort member with a genetically confirmed maternally inherited mDNA mutation. Information on cancer was obtained by linkage to the Danish Cancer Register. Standardised incidence ratios (SIRs) were used to assess the relative risk of cancer.Results:During 7334 person-years of follow-up, 19 subjects developed a primary cancer. The corresponding SIR for any primary cancer was 1.06 (95% confidence interval 0.68-1.63). Subgroup analyses according to mutational subtype yielded similar results, for example, a SIR of 0.94 (95% CI 0.53 to 1.67) for the m.3243A>G maternally inherited mDNA mutation, cases=13.Conclusions:Patients with mitochondrial dysfunction do not appear to be at increased risk of cancer compared with the general population.British Journal of Cancer advance online publication, 5 March 2015; doi:10.1038/bjc.2015.66
    British Journal of Cancer 03/2015; 112(6). DOI:10.1038/bjc.2015.66 · 4.82 Impact Factor
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    ABSTRACT: Introduction: Muscular dystrophy caused by LAMA2-gene mutations is an autosomal recessive disease typically presenting as a severe, early-onset congenital muscular dystrophy (CMD). However, milder cases with a limb-girdle type muscular dystrophy (LGMD) have been described. Methods: In this study, we assessed the frequency and phenotypic spectrum of LAMA2-related muscular dystrophy in cohorts of CMD (n=18) and LGMD2 (n=128) identified in the last 15 years in eastern Denmark. The medical history, brain-MRI, muscle pathology, muscle laminin-α2 expression, and genetic analyses were assessed. Results: Molecular genetics revealed 2 pathogenic LAMA2 mutations in 5/18 CMD and 3/128 LGMD patients, corresponding to a LAMA2-mutation frequency of 28% in the CMD and 2.3% in the LGMD cohorts, respectively. Discussion: This study demonstrates a wide clinical spectrum of LAMA2-related muscular dystrophy and its prevalence in an LGMD2 cohort, which indicates that LAMA2 muscular dystrophy should be included in the LGMD2 nomenclature. This article is protected by copyright. All rights reserved. Copyright © 2015 Wiley Periodicals, Inc., a Wiley company.
    Muscle & Nerve 02/2015; DOI:10.1002/mus.24588 · 2.31 Impact Factor
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    ABSTRACT: We investigated a subject with an isolated cytochrome c oxidase (COX) deficiency presenting with an unusual phenotype characterised by neuropathy, exercise intolerance, obesity, and short stature. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) analysis showed an almost complete lack of COX assembly in subject fibroblasts, consistent with the very low enzymatic activity, and pulse-labelling mitochondrial translation experiments showed a specific decrease in synthesis of the COX1 subunit, the core catalytic subunit that nucleates assembly of the holoenzyme. Whole exome sequencing identified compound heterozygous mutations (c.199dupC, c.215A>G) in COA3, a small inner membrane COX assembly factor, resulting in a pronounced decrease in the steady-state levels of COA3 protein. Retroviral expression of a wild-type COA3 cDNA completely rescued the COX assembly and mitochondrial translation defects, confirming the pathogenicity of the mutations, and resulted in increased steady-state levels of COX1 in control cells, demonstrating a role for COA3 in the stabilisation of this subunit. COA3 exists in an early COX assembly complex that contains COX1 and other COX assembly factors including COX14 (C12orf62), another single pass transmembrane protein that also plays a role in coupling COX1 synthesis with holoenzyme assembly. Immunoblot analysis showed that COX14 was undetectable in COA3 subject fibroblasts, and that COA3 was undetectable in fibroblasts from a COX14 subject, demonstrating the interdependence of these two COX assembly factors. The mild clinical course in this patient contrasts with nearly all other cases of severe COX assembly defects that are usually fatal early in life, and underscores the marked tissue-specific involvement in mitochondrial diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
  • Clinical Neurology and Neurosurgery 01/2015; 130C. DOI:10.1016/j.clineuro.2015.01.010 · 1.25 Impact Factor
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    ABSTRACT: To assess the degree and progression of cardiac involvement in patients with limb-girdle type 2 (LGMD2) and Becker muscular dystrophies (BMD). A follow-up study of 100 LGMD2 (types A-L) and 30 BMD patients assessed by electrocardiogram (ECG) and echocardiography, supplemented by Holter-monitoring at follow-up. After a median of 8.9years (range 0.4-13.7), twelve patients had died: LGMD2 (n=10, mean age 61±11years), BMD (n=2, age 43 and 45years). Of the remaining 118 patients, 89 completed follow-up: LGMD2 (n=64, age 48±13years) and BMD (n=25, age 40±13years). In BMD, LVEF decreased from 60% (10-62) to 50% (10-64), p=0.02 corresponding to a one percentage drop annually. Among patients with LGMD2, LVEF decreased significantly in patients with LGMD type 2I (n=28) from 59% (15-72) to 55% (20-61), p=0.03, i.e. a 0.4 percentage drop annually, and LVEF≤50% was associated with increased mortality in this subgroup. In LGMD2E, 3/5 patients (60%) at baseline and 4/5 (80%) at follow-up had LVEF≤50%. ECG abnormalities were non-progressive in BMD and in all subgroups of LGMD2. SVT and NSVT were present in both groups: BMD (3/14 (21%) and (2/14 (14%)), LGMD2 (16/51 (31%) and 8/51 (16%)), respectively, all asymptomatic. LVEF decreased significantly in patients with BMD and LGMD2I, and the majority of patients with LGMD2E had left ventricular systolic dysfunction. This study emphasizes the need for tailored regular cardiac assessments according to molecular diagnosis with special focus on BMD and LGMD types 2I and 2E. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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    Kira P Prahm, Nanna Witting, John Vissing
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    ABSTRACT: The 6-minute walk test is widely used to assess functional status in neurological disorders. However, the test is subject to great inter-test variability due to fluctuating motivation, fatigue and learning effects. We investigated whether inter-test variability of the 6MWT can be reduced by heart rate correction. Sixteen patients with neuromuscular diseases, including Facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, Charcot-Marie-Tooths, Dystrophia Myotonica and Congenital Myopathy and 12 healthy subjects were studied. Patients were excluded if they had cardiac arrhythmias, if they received drug treatment for hypertension or any other medical conditions that could interfere with the interpretation of the heart rate and walking capability. All completed three 6-minute walk tests on three different test-days. Heart rate was measured continuously. Successive standard 6-minute walk tests showed considerable learning effects between Tests 1 and 2 (4.9%; P = 0.026), and Tests 2 and 3 (4.5%; P = 0.020) in patients. The same was seen in controls between Tests 1 and 2 (8.1%; P = 0.039)). Heart rate correction abolished this learning effect. A modified 6-minute walk test, by correcting walking distance with average heart rate during walking, decreases the variability among repeated 6-minute walk tests, and should be considered as an alternative outcome measure to the standard 6-minute walk test in future clinical follow-up and treatment trials.
    PLoS ONE 12/2014; 9(12):e114273. DOI:10.1371/journal.pone.0114273 · 3.53 Impact Factor
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    ABSTRACT: In healthy individuals post-exercise protein supplementation increases muscle protein anabolism. In patients with muscular dystrophies, aerobic exercise improves muscle function, but the effect of exercise on muscle protein balance is unknown. Therefore, we investigated 1) muscle protein balance before, during, and after exercise and 2) the effect of post-exercise protein-carbohydrate supplementation on muscle protein balance in patients with muscular dystrophies. In 17 patients (7 women and 10 men, age 33 ± 11 years (18-52), BMI: 22 ± 3 kg/m2 (16-26)) and 8 healthy matched controls (3 women and 5 men, age 33 ± 13 years (19-54), BMI: 23 ± 3 kg/m2 (19-27)), muscle protein synthesis, breakdown, and fractional synthesis rates (FSR) were measured across the leg using tracer dilution methodology on two occasions; with and without oral post-exercise protein-carbohydrate supplementation. In patients, muscle protein breakdown increased in the recovery period (11 ± 1 µmol phenylalanine/min) versus rest (8 ± 1 µmol phenylalanine/min, P = 0.02) enhancing net muscle protein loss. In contrast, post-exercise protein-carbohyddrate supplementation reduced protein breakdown, abolished net muscle protein loss and increased the muscle FSR in patients (0.04 to 0.06 % per hour, P = 0.03). In conclusion, post-exercise protein-carbohydrate supplementation reduces skeletal mixed muscle protein breakdown, enhances FSR, resulting in a reduced net muscle loss in patients with muscular dystrophies. The findings suggest that post-exercise protein-carbohydrate supplementation could be an important add-on to exercise training therapy in muscular dystrophies, and long-term studies of post-exercise protein-carbohydrate supplementation are warranted in these conditions. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    AJP Regulatory Integrative and Comparative Physiology 11/2014; 308(2):ajpregu.00321.2014. DOI:10.1152/ajpregu.00321.2014 · 3.53 Impact Factor
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    ABSTRACT: A 10-year-old girl presented with exercise intolerance, learning difficulty, and muscle weakness in a limb girdle distribution. She had delayed achievement of motor milestones and difficulties with social interaction at pre-school age. Muscle biopsy showed no myopathic or dystrophic features, but 90% COX negative fibres and ragged blue fibres. Respiratory chain enzyme analysis in muscle showed a combined deficiency and mitochondrial DNA sequencing revealed the presence of an m.4450G>A mutation in the MT-TM gene encoding the tRNA for methionine. The mutation was only detected in mtDNA extracted from muscle and skin fibroblast, and could not be found in other tissues or in the mother. This is the second patient reported in the literature with a mitochondrial myopathy due to a mt-tRNA(Met) mutation. The first patient, a 30-year-old woman, presented with exercise intolerance, limb girdle muscle weakness, lactic acidosis, learning difficulty, and growth retardation in early childhood. Thus, the two patients exhibit strikingly overlapping phenotypes. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 11/2014; 19(1). DOI:10.1016/j.ejpn.2014.10.006 · 1.93 Impact Factor
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    ABSTRACT: IntroductionWe investigated the effect of 12 weeks of cycle ergometer training in patients with Spinal Muscular Atrophy type III (SMA III), a hereditary motor neuron disease with progressive muscle weakness and atrophy.Methods Six SMA III patients and 9 healthy subjects completed a 12-week training program, performing 42, 30-minute sessions exercising at 65-70% of maximal oxygen uptake (VO2max). VO2max, muscle strength, functional tests, and self-reported Activities of Daily Living were assessed before and after the training.ResultsTraining induced a 27 ± 3% increase in VO2max (17 ± 2 to 21 ± 2 ml/kg/min, P<0.001) in patients. However, fatigue was a major complaint and caused 1 patient to drop out, increased the need for sleep in 3 patients, and led to training modifications in 2 patients.DiscussionCycle exercise improves VO2max in SMA III without causing muscle damage, but it also induces significant fatigue. This warrants investigations into alternative training methods to improve exercise capacity in SMA III patients. This article is protected by copyright. All rights reserved.
    Muscle & Nerve 11/2014; DOI:10.1002/mus.24527 · 2.31 Impact Factor
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    ABSTRACT: Bastin et al. question the negative results of treating patients with carnitine palmitoyltransferase (CPT) II deficiency and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency with bezafibrate based on findings in their open-labeled, uncontrolled trial with bezafibrate in patients with CPTII deficiency. Their studies showed grade C evidence for an effect based on in vitro findings in myoblasts and on questionnaires to the patients and the recording of episodes of myoglobinuria in the patients (Bonnefont et al. 2009). None of these assessments evaluated specific clinical or biochemical parameters reflecting the consequences of CPTII deficiency during exercise in adults. Our randomized, double-blind, placebo-controlled study, showing grade B evidence for no effect of bezafibrate in patients with CPTII and VLCAD deficiencies, demonstrated no improvements in muscle fatty acid oxidation or exercise tolerance after bezafibrate treatment (Orngreen et al. 2014).Bastin and coworkers crit ...
    Journal of Inherited Metabolic Disease 10/2014; 38(2). DOI:10.1007/s10545-014-9779-3 · 4.14 Impact Factor
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    ABSTRACT: Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase in glycogen storage that disrupts contractile function and/or 2) a reduced substrate turnover below the block, which inhibits skeletal muscle ATP production. Immobility is associated with metabolic alterations in muscle leading to an increased dependence on glycogen use and a reduced capacity for fatty acid oxidation. Such changes may be detrimental for persons with GSD from a metabolic perspective. However, exercise may alter skeletal muscle substrate metabolism in ways that are beneficial for patients with GSD, such as improving exercise tolerance and increasing fatty acid oxidation. In addition, a regular exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies that have examined the effect of regular exercise training in different types of GSD. Finally, we consider how oral substrate supplementation can improve exercise tolerance and we discuss the precautions that apply to persons with GSD that engage in exercise.
    Journal of Inherited Metabolic Disease 10/2014; DOI:10.1007/s10545-014-9771-y · 4.14 Impact Factor
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    ABSTRACT: Objective: Patients with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy lack neuronal nitric oxide synthase (nNOS). nNOS mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosphodiesterase 5 (PDE5) inhibitor (sildenafil) improves skeletal and cardiac muscle performance. Sildenafil also improves blood flow in patients with BMD. We therefore hypothesized that sildenafil would improve blood flow, maximal work capacity, and heart function in patients with BMD. Methods: A randomized, double-blind, placebo-controlled crossover design with two 4-week periods of treatment, separated by 2-week washout was used. We assessed brachial artery blood flow during maximal handgrip exercise, 6-minute walk test, maximal oxidative capacity, and life quality; cardiac function was evaluated by magnetic resonance imaging (MRI) at rest and during maximal handgrip exercise. Muscle nNOS and PDE5 were tested with Western blotting in 5 patients. Results: Sixteen patients completed all skeletal muscle evaluations, and 13 completed the cardiac MRI investigations. Sildenafil had no effect on any of the outcome parameters. No serious adverse effects were recorded. PDE5 and nNOS were deficient in 5 of 5 biopsies. Interpretation: Despite positive evidence from animal models of dystrophinopathy and physiological findings in patients with BMD, this double-blind, placebo-controlled clinical study showed no effect of sildenafil on blood flow, maximal work capacity, and heart function in adults with BMD. This discrepancy may be explained by a significant downregulation of PDE5 in muscle.
    Annals of Neurology 10/2014; 76(4). DOI:10.1002/ana.24216 · 11.91 Impact Factor
  • Acta ophthalmologica 10/2014; DOI:10.1111/aos.12558 · 2.51 Impact Factor
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    ABSTRACT: The European Union has funded the development of a new disease registry for McArdle disease and other rare glyco (geno) lytic disorders presenting with exercise intolerance. The aim of the project is to identify as many patients as possible across all European countries and to collect important natural history and epidemiological data. Clinicians working in the European Union (EU) and patients with McArdle disease or other rare glyco (geno) lytic disorders presenting with exercise intolerance from the EU are able to participate in this project. Registration is via a secure web platform accessed through the EUROMAC website Both patients and doctors will need to supply epidemiological and clinical information. Data will be anonymised to ensure participants’ protection. We hope to create the largest international cohort of people with such rare conditions. Data on epidemiology and natural history will be generated, supporting knowledge about these rare disorders. We hope to increase awareness of these disorders and the website will signpost patients and clinicians to diagnostic and clinical centres of excellence across Europe. We plan to develop standards of care which will be posted on the website and we hope that the registry will be the gateway to future large scale multi-centre clinial trials. The EUROMAC is an international registry for patients with McArdle disease and other rare glyco (geno) lytic disorders presenting with exercise intolerance and it is open to all EU residents. Further information is presented online in the EUROMAC website We seek to recruit as many European partners as possible and welcome collaborators and volunteers both from health services and patient support organisations.
    Neuromuscular Disorders 10/2014; 24(9-10):890. DOI:10.1016/j.nmd.2014.06.321 · 3.13 Impact Factor
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    ABSTRACT: In this study, involvement of paraspinal muscles in 50 patients with facioscapulohumeral dystrophy (FSHD) was evaluated using MRI.
    Neurology 08/2014; DOI:10.1212/WNL.0000000000000828 · 8.30 Impact Factor
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    ABSTRACT: Background and purposePatients with myotonic dystrophy type 1 (DM1) have an increased incidence of endocrine dysfunction. In this study, the temporal evolution of endocrine dysfunction in patients with DM1 was investigated.Methods Endocrine function was assessed in 68 patients with DM1, in whom endocrine function had been followed, on average, for 8 years. The endocrine function was assessed by measuring the concentration of hormones and metabolites in blood and by validating libido with questionnaires.ResultsAt baseline, 30 of the 68 patients presented with at least one hormonal dysfunction. When re-evaluated after 8 years, 57 of 68 patients had endocrine dysfunction. Diabetic patients had increased from one to four. At follow-up, hyperparathyroidism occurred in 25% and abnormal thyroid-stimulating hormone in 21%, compared with 14% and 9% at baseline. Sixteen of 33 men had increased luteinizing hormone levels compared with seven at baseline.Conclusions Our findings show that endocrine abnormalities amongst patients with DM1 increase over time. Based on these findings it is suggested that correctable endocrine abnormalities should be monitored periodically in this patient group.
    European Journal of Neurology 08/2014; DOI:10.1111/ene.12542 · 3.85 Impact Factor
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    ABSTRACT: Background Myotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant.The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography.Methods We selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring.Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR.ResultsMyocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/m2 (43¿83) vs. 46 g/m2 (36¿64), p = 0.02), increased left atrial volume (median (range) 52 ml/m2 (36¿87) vs. 46 ml/m2 (35¿69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38¿71) vs. 66% (60¿80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18).Conclusion Patients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1.
    Journal of Cardiovascular Magnetic Resonance 08/2014; 16(1):59. DOI:10.1186/PREACCEPT-1991790702125713 · 5.11 Impact Factor

Publication Stats

3k Citations
1,212.01 Total Impact Points


  • 2015
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1988–2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2007–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
    • Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust
      Oswestry, England, United Kingdom
    • Selcuk University
      • Department of Pediatrics
      Konya, Konya, Turkey
    • Copenhagen Trial Unit
      København, Capital Region, Denmark
  • 2013
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
    • RehabiliteringsCenter for Muskelsvind
      København, Capital Region, Denmark
  • 2012
    • Children's Heart Center
      Las Vegas, Nevada, United States
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hospital Universitari de Bellvitge
      l'Hospitalet de Llobregat, Catalonia, Spain
  • 1996–2010
    • National University (California)
      San Diego, California, United States
  • 2002–2007
    • Rigshospitalet
      • Neuromuscular Research Unit
      København, Capital Region, Denmark
  • 2001–2007
    • The John F. Kennedy Institute, Denmark
      Glostrup, Capital Region, Denmark
  • 2006
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
    • Glostrup Hospital
      København, Capital Region, Denmark
  • 2005
    • University of Copenhagen
      • The Copenhagen Muscle Research Centre
      København, Capital Region, Denmark
    • Aarhus University Hospital
      Aarhus, Central Jutland, Denmark
  • 2004–2005
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 1994
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 1989–1994
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States