John Vissing

Copenhagen University Hospital, København, Capital Region, Denmark

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Publications (195)1060.03 Total impact

  • [Show abstract] [Hide abstract]
    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; · 2.31 Impact Factor
  • Journal of Inherited Metabolic Disease 10/2014; · 4.07 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; · 4.07 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 http://euromacregistry.eu/. 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 http://euromacregistry.eu/. 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. · 3.46 Impact Factor
  • Acta ophthalmologica 10/2014; · 2.44 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; · 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; · 4.16 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. · 4.44 Impact Factor
  • Annals of Neurology 07/2014; · 11.19 Impact Factor
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    ABSTRACT: Background and purposeMyotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted.MethodsDM was identified using the National Danish Patient Registry and results of genetic testing. Information on cancer was obtained from the Danish Cancer Registry. A population-based cohort of 5 757 565 individuals with at least one relative was established using the Danish Family Relations Database based on kinship links in the Danish Civil Registration System. Familial aggregation of cancer was evaluated by (incidence) rate ratios (RRs) comparing the rate of cancer amongst relatives of patients with DM from 1977 to 2010 (exposed) with the rate of cancer amongst persons with a relative of the same type but without DM (non-exposed).ResultsIn first-degree relatives of individuals with DM the adjusted RR of cancer was 0.89 (95% confidence interval 0.71–1.12) overall, and in stratified analyses 0.68 (0.37–1.12) before age 50 and 0.96 (0.74–1.23) at age 50 or older.Conclusions The present study does not support an increased risk of cancer in non-DM relatives of DM patients suggesting that cancer and DM are associated through derived effects of the DM genotype.
    European Journal of Neurology 05/2014; · 4.16 Impact Factor
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    ABSTRACT: To quantify the association between myotonic dystrophy (DM) and cardiac disease in a nationwide cohort. We identified a nationwide cohort of 1146 DM patients (period 1977-2011) using the National Patient Registry (NPR) and a subcohort of 485 patients who had undergone genetic testing for DM1. Information on incident cardiac diseases was obtained from the NPR. We estimated standardized incidence ratios (SIRs) of cardiac disease compared with the background population, overall and according to selected diagnostic subgroups (cardiomyopathy, heart failure, conduction disorders, arrhythmias, and device implantation). In the DM cohort, SIR for any cardiac disease was 3.42 [95% confidence interval (CI) 3.01-3.86]; for a cardiac disease belonging to the selected subgroups 6.91 (95% CI: 5.93-8.01) and for other cardiac disease 2.59 (95% CI: 2.03-3.25). For a cardiac disease belonging to the selected subgroups, the risk was particularly high in the first year after DM diagnosis [SIR 15.4 (95% CI: 10.9-21.3)] but remained significantly elevated in subsequent years [SIR 6.07 (95% CI: 5.11-7.16]). The risk was higher in young cohort members [e.g. 20-39 years: SIR 18.1 (95% CI: 12.3-25.8)] compared with older [e.g. 60-79 years: SIR 3.99 (95% CI: 2.98-5.23)] but remained significantly increased in all age categories. Results were similar in separate analyses of the genetically confirmed DM1 patients. Myotonic dystrophy is strongly associated with cardiac disease. The risk is pronounced in the young and remains elevated throughout life, stressing the importance of lifelong cardiac follow-up from time of DM diagnosis.
    European Heart Journal 04/2014; · 14.72 Impact Factor
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    ABSTRACT: Patients with myotonic dystrophy type 1 (DM1) have a three-fold higher risk of sudden cardiac death (SCD) than age-matched healthy controls. Despite numerous attempts to define the cardiac phenotype and natural history, existing literature suffers from low power, selection-bias and lack of controls. Thus, the optimal strategy for assessing cardiac involvement in DM1 is unclear. In this large single-centre study, we evaluated 129 unselected DM1 patients (49.6% men), mean (SD) age 44 (14.7) years with family history, physical examination, electrocardiogram (ECG), echocardiography, Holter-monitoring and muscle strength testing. Cardiac involvement was found in 71 patients (55%) and included: 1) Conduction abnormalities: atrio-ventricular block grade I (AVB grade I) (23.6%), AVB grade II (5.6%), right/left bundle branch block (5.5/3.2%) and prolonged QTc (7.2%); 2) arrhythmias: atrial fibrillation/flutter (4.1%), other supraventricular tachyarrhythmia (7.3%) and non-sustained ventricular tachycardia (4.1%); and 3) structural abnormalities: left ventricular systolic dysfunction (20.6%) and reduced global longitudinal strain (21.7%). A normal ECG was not significantly associated with normal findings on Holter-monitoring or echocardiography. Patients with abnormal cardiac findings had weaker muscle strength than those with normal cardiac findings: ankle dorsal flexion (median (range) 4.5 (0-5) vs. 5.0 (2.5-5), p=0.004) and handgrip (median 4.0 (0-5) vs. 4.50 (2-5), p=0.02). The cardiac phenotype of DM1 includes a high prevalence of conduction disorders, arrhythmias and risk factors of SCD. Systematic cardiac screening with ECG, Holter-monitoring and echocardiography is needed in order to make a proper characterization of cardiac involvement in DM1.
    International journal of cardiology 03/2014; · 6.18 Impact Factor
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    ABSTRACT: Objectives To assess skeletal muscle weakness and progression as well as the cardiopulmonary involvement in oculopharyngeal muscular dystrophy (OPMD). Materials and methodsCross-sectional study including symptomatic patients with genetically confirmed OPMD. Patients were assessed by medical history, ptosis, ophthalmoplegia, facial and limb strength, and swallowing capability. Cardiopulmonary function was evaluated using forced expiratory capacity in 1 s (FEV1), electrocardiogram (ECG), Holter monitoring, and echocardiography. ResultsWe included 13 symptomatic patients (six males, mean age; 64 years (41–80) from 8 families. Ptosis was the first symptom in 8/13 patients followed by limb weakness in the remaining 5 patients Dysphagia was never the presenting symptom. At the time of examination, all affected patients had ptosis or had previously been operated for ptosis, while ophthalmoplegia was found in 9 patients. Dysphagia, tested by cold-water swallowing test, was abnormal in 9 patients (17-116 s, ref <8 s). Six patients could not climb stairs of whom two were wheelchair bound and one used a rollator. Six patients had reduced FEV1 (range 23%–59%). No cardiac involvement was identified. Conclusions Limiting limb weakness is common in OPMD and can even be the presenting symptom of the disease. In contrast, dysphagia was not the initial symptom in any of our patients, although it was obligatory for diagnosing OPMD before genetic testing became available. Mild respiratory dysfunction, but no cardiac involvement, was detected.
    Acta Neurologica Scandinavica 03/2014; · 2.47 Impact Factor
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    ABSTRACT: http://euromacregistry.eu/
    Neuromuscular Disorders 03/2014; 24(Supplement 1):S25. · 3.46 Impact Factor
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    ABSTRACT: Objective: Ceramides are precursors of complex sphingolipids (SLs), which are important for normal functioning of both the developing and mature brain. Altered SL levels have been associated with many neurodegenerative disorders, including epilepsy, although few direct links have been identified between genes involved in SL metabolism and epilepsy. Methods: We used quantitative real-time PCR, Western blotting, and enzymatic assays to determine the mRNA, protein, and activity levels of ceramide synthase 2 (CERS2) in fiibroblasts iso-lated from parental control subjects and from a patient diagnosed with progres-sive myoclonic epilepsy (PME). Mass spectrometry and fluorescence microscopy were used to examine the effects of reduced CERS2 activity on cel-lular lipid composition and plasma membrane functions. Results: We identify a novel 27 kb heterozygous deletion including the CERS2 gene in a proband diagnosed with PME. Compared to parental controls, levels of CERS2 mRNA, protein, and activity were reduced by ~50% in fibroblasts isolated from this proband, resulting in significantly reduced levels of ceramides and sphingomye-lins containing the very long-chain fatty acids C24:0 and C26:0. The change in SL composition was also reflected in a reduction in cholera toxin B immuno-fluorescence, indicating that membrane composition and function are altered. Interpretation: We propose that reduced levels of CERS2, and consequently diminished levels of ceramides and SLs containing very long-chain fatty acids, lead to development of PME.
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    ABSTRACT: To assess whether bezafibrate increases fatty acid oxidation (FAO) and lowers heart rate (HR) during exercise in patients with carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies. This was a 3-month, randomized, double-blind, crossover study of bezafibrate in patients with CPT II (n = 5) and VLCAD (n = 5) deficiencies. Primary outcome measures were changes in FAO, measured with stable-isotope methodology and indirect calorimetry, and changes in HR during exercise. Bezafibrate lowered low-density lipoprotein, triglyceride, and free fatty acid concentrations; however, there were no changes in palmitate oxidation, FAO, or HR during exercise. Bezafibrate does not improve clinical symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies. These findings indicate that previous in vitro studies suggesting a therapeutic potential for fibrates in disorders of FAO do not translate into clinically meaningful effects in vivo. This study provides Class I evidence that bezafibrate 200 mg 3 times daily is ineffective in improving changes in FAO and HR during exercise in adults with CPT II and VLCAD deficiencies.
    Neurology 01/2014; · 8.30 Impact Factor
  • Nanna Witting, John Vissing
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    ABSTRACT: IMPORTANCE Congenital myasthenic syndromes (CMSs) are increasingly recognized as causes of muscle fatigue and weakness. However, treatment of individual syndromes has been described only in small case series. OBJECTIVE To analyze the information published thus far concerning the effect of pharmacologic treatment of one of the most common subtypes of CMS, downstream of tyrosine kinase 7 (DOK7) CMS. EVIDENCE REVIEW In a search of the PubMed database, we found 16 publications describing the response to medication in 122 individuals with DOK7 deficiency. The last search was performed August 15, 2013. If more than 1 article had been published by the same group, a comparison of the participants in the studies was made, and data appearing more than once were excluded. FINDINGS Positive effects were observed in 6 of 66 patients who received an acetylcholinesterase inhibitor, 65 of 69 patients who received ephedrine or salbutamol, 18 of 29 who were given 3,4-diaminopyridine, and 13 of 16 individuals who received a combination of these drugs. Our analysis found no evidence that age at disease onset, age at treatment start, drug dosage, or mutation type influenced treatment results. The magnitude of treatment effect with ephedrine or salbutamol seems to increase gradually, peaking after approximately 6 to 8 months. Treatment with acetylcholinesterase inhibitors resulted in worsened conditions for most patients. CONCLUSIONS AND RELEVANCE This analysis suggests that (1) ephedrine or salbutamol is the first choice of treatment in DOK7 CMS; (2) 3,4-diaminopyridine may provide additional benefi; (3) it is never too late to initiate treatment; and (4) in contrast to acquired myasthenia gravis, treatment with acetylcholinesterase inhibitors should be avoided in DOK7 CMS.
    JAMA neurology. 01/2014;
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    ABSTRACT: Objective: Ceramides are precursors of complex sphingolipids (SLs), which are important for normal functioning of both the developing and mature brain. Altered SL levels have been associated with many neurodegenerative disorders, including epilepsy, although few direct links have been identified between genes involved in SL metabolism and epilepsy. Methods: We used quantitative real-time PCR, Western blotting, and enzymatic assays to determine the mRNA, protein, and activity levels of ceramide synthase 2 (CERS2) in fiibroblasts iso-lated from parental control subjects and from a patient diagnosed with progres-sive myoclonic epilepsy (PME). Mass spectrometry and fluorescence microscopy were used to examine the effects of reduced CERS2 activity on cel-lular lipid composition and plasma membrane functions. Results: We identify a novel 27 kb heterozygous deletion including the CERS2 gene in a proband diagnosed with PME. Compared to parental controls, levels of CERS2 mRNA, protein, and activity were reduced by ~50% in fibroblasts isolated from this proband, resulting in significantly reduced levels of ceramides and sphingomye-lins containing the very long-chain fatty acids C24:0 and C26:0. The change in SL composition was also reflected in a reduction in cholera toxin B immuno-fluorescence, indicating that membrane composition and function are altered. Interpretation: We propose that reduced levels of CERS2, and consequently diminished levels of ceramides and SLs containing very long-chain fatty acids, lead to development of PME.
    Annals of Clinical and Translational Neurology. 01/2014; 1(2):88-98.
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    ABSTRACT: Pompe disease is a rare, inherited metabolic myopathy characterized by progressive weakness of the proximal limb and respiratory muscles. We report the findings from four patients with late-onset Pompe disease treated with α-glucosidase (Myozyme) for two (n = 2) and six (n = 2) years, and monitored with isokinetic dynamometry, 6-minute walking test (6MWT), and vital capacity. Patients were evaluated after 6, 12, 24, 36, 48, 60, and 72 months. In two patients, muscle size estimated by MRI and DXA scanning were also performed prior to and following six months of treatment. After two years of α-glucosidase treatment, maximal isokinetic muscle strength increased by 11 (0–50) % [median (range)] and 6MWT improved by 18 (2–40) %. In the two patients treated for six years, the increase in muscle strength stabilized at 40% and 6MWT stabilized at 32%. The improvements primarily occurred during the first six months of treatment. Interestingly, the weakest muscle groups seemed to benefit more than those less affected, and greater improvements occurred for flexor muscles compared to extensor muscles. Vital capacity did not improve on treatment.
    Molecular Genetics and Metabolism 01/2014; · 2.83 Impact Factor

Publication Stats

2k Citations
1,060.03 Total Impact Points

Institutions

  • 2008–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2002–2014
    • University of Copenhagen
      • • Department of Nutrition, Exercise and Sports
      • • Rigshospitalet
      • • The Copenhagen Muscle Research Centre
      København, Capital Region, Denmark
  • 1988–2014
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2013
    • Aarhus University
      Aarhus, Central Jutland, Denmark
    • Newcastle University
      • Institute of Genetic Medicine
      Newcastle upon Tyne, ENG, United Kingdom
    • RehabiliteringsCenter for Muskelsvind
      København, Capital Region, Denmark
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
  • 2000–2013
    • Glostrup Hospital
      • • Department of Ophthalmology
      • • Department of Neurology
      Copenhagen, Capital Region, Denmark
  • 2010–2012
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust
      Oswestry, England, United Kingdom
    • Selcuk University
      • Department of Pediatrics
      Konya, Konya, Turkey
  • 2005–2007
    • Rigshospitalet
      • • Department of Clinical Genetics
      • • Department of Neurology
      Copenhagen, Capital Region, Denmark
  • 2003
    • University of Antwerp
      • VIB Department of Molecular Genetics
      Antwerpen, VLG, Belgium
  • 2001
    • The John F. Kennedy Institute, Denmark
      Glostrup, Capital Region, Denmark
  • 1994
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 1989–1994
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States