John Vissing

Copenhagen University Hospital, København, Capital Region, Denmark

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Publications (270)1374.17 Total impact

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    ABSTRACT: Introduction: We studied the functional effects of combined strength and aerobic anti-gravity training in severely affected patients with Becker and Limb-Girdle muscular dystrophies. Methods: Eight patients performed 10-week progressive combined strength (squats, calf raises, lunges) and aerobic (walk/run, jogging in place or high knee-lift) training 3 times/week in a lower-body positive pressure environment. Closed-kinetic-chain leg muscle strength, isometric knee strength, rate of force development (RFD), and reaction time were evaluated. Results: Baseline data indicated an intact neural activation pattern but showed compromised muscle contractile properties. Training (compliance 91%) improved functional leg muscle strength. Squat series performance increased 30%, calf raises 45%, and lunges 23%. Conclusion: Anti-gravity training improved closed-kinetic-chain leg muscle strength despite no changes in isometric knee extension strength and absolute RFD. The improved closed-kinetic-chain performance may relate to neural adaptation involving motor learning and/or improved muscle strength of other muscles than the weak knee extensors. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Muscle & Nerve
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    ABSTRACT: Introduction: Congenital myopathies (CM) often affect contractile proteins of the sarcomere, which could render patients susceptible to exercise-induced muscle damage. We investigated if exercise is safe and beneficial in patients with CM. Methods: Patients exercised on a stationary bike for 30 minutes, three times weekly, for 10 weeks at 70% of their maximal oxygen uptake (VO2max). Creatine kinase (CK) was monitored as a marker of muscle damage. VO2max, functional tests, and questionnaires evaluated efficacy. Results: Sixteen patients with CM were included in a controlled study. VO2max increased by 14% (range, 6-25%; 95% CI 7-20; p < 0.001) in the seven patients who completed training, and tended to decrease in a non-intervention group (n = 7; change -3.5%; range, -11-3%, p = 0.083). CK levels were normal and remained stable during training. Baseline Fatigue Severity Scale scores were high, 4.9 (SE 1.9), and tended to decrease (to 4.4 (SE 1.7); p = 0.08) with training. Nine patients dropped out of the training program. Fatigue was the major single reason. Conclusions: Ten weeks of endurance training is safe and improves fitness in patients with congenital myopathies. The training did not cause sarcomeric injury, even though sarcomeric function is affected by the genetic abnormalities in most patients with CM. Severe fatigue, which characterizes patients with CM, is a limiting factor for initiating training in CM, but tends to improve in those who train. Trial registration: The Regional Committee on Health Research Ethics of the Capital Region of Denmark H-2-2013-066 and ClinicalTrials.gov H2-2013-066.
    Preview · Article · Jan 2016 · PLoS ONE
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    ABSTRACT: Pathomechanisms of spinal and bulbar muscular atrophy (SBMA) have been extensively investigated and are partially understood, but no effective treatment is currently available for this disabling disorder. Its rarity, the slow disease progression, and lack of sensitive-to-change outcome measures render design and conduction of clinical trials a challenging task. Therefore, it is fundamental to strengthen the network of clinical centers interested in SBMA for clinical trial readiness. We propose to create and maintain an International SBMA Registry where as many well-characterized patients as possible can be included, with the following aims: facilitate planning of clinical trials and recruitment of patients, define natural history of the disease, characterize epidemiology, develop standards of care, and inform the community of patients about research progresses and ongoing trials. We also aim at developing harmonized and coordinated biorepositories. The experience obtained during the last years in the field of other neuromuscular disorders and of Huntington disease offers valuable precedents.
    No preview · Article · Jan 2016 · Journal of Molecular Neuroscience
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    ABSTRACT: Objective: This methodologic study investigates if the 2-minute walk test (2MWT) can be a valid alternative to the 6-minute walk test (6MWT) to describe walking capability in patients with neuromuscular diseases. Methods: Patients (n = 115) with different neuromuscular diseases were invited to participate on 2 test days, each consisting of 1 2MWT and 1 6MWT separated by a minimum 30-minute period of rest. The order of the walk tests was randomly assigned via sealed envelopes. A group of 38 healthy controls completed 1 6MWT. Results: The mean walking distance for the 2MWT was 142.8 meters and for the 6MWT 405.3 meters. The distance walked in the 2MWT was highly correlated to the distance walked in the 6MWT (r = 0.99, p < 0.001). There was a significant decrease in walking speed from the first to last minute in the 6MWT, both among patients and healthy controls, which was not evident in the 2MWT. Results were consistent across diagnoses and levels of disease severity. Conclusion: The 2MWT is a potential alternative to the 6MWT to describe walking capability among patients with neuromuscular diseases during clinical trials.
    Preview · Article · Jan 2016 · Neurology
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    ABSTRACT: Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A mutations showed loss-of-function of the mutant Nav1.4 channels. All, apart from one, of the mutations either caused fully non-functional channels, or resulted in a reduced channel activity. Each of the affected cases carried at least one full loss-of-function mutation. In five out of six families, a second loss-of-function mutation was present on the trans allele. These functional results provide convincing evidence for the pathogenicity of the identified mutations and suggest that different degrees of loss-of-function in mutant Nav1.4 channels are associated with attenuation of the skeletal muscle action potential amplitude to a level insufficient to support normal muscle function. The results demonstrate that recessive loss-of-function SCN4A mutations should be considered in patients with a congenital myopathy.
    Full-text · Article · Dec 2015 · Brain
  • Nanna Witting · Linda K Andersen · John Vissing
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    ABSTRACT: Classically, myopathies are categorized according to limb or cranial nerve muscle affection, but with the growing use of magnetic resonance imaging it has become evident that many well-known myopathies have significant involvement of the axial musculature. New disease entities with selective axial muscle involvement have also been described recently, but overall the axial myopathy is unexplored. We performed a PubMed search using the search terms 'myopathy', 'paraspinal', 'axial' and 'erector'. Axial myopathy was defined as involvement of paraspinal musculature. We found evidence of axial musculature involvement in the majority of myopathies in which paraspinal musculature was examined. Even in diseases named after a certain pattern of non-axial muscle affection, such as facioscapulohumeral and limb girdle muscular dystrophies, affection of the axial musculature was often severe and early, compared to other muscle groups. Very sparse literature evaluating the validity of clinical assessment methods, electromyography, muscle biopsy and magnetic resonance imaging was identified and reference material is generally missing. This article provides an overview of the present knowledge on axial myopathy with the aim to increase awareness and spur interest among clinicians and researchers in the field.
    No preview · Article · Dec 2015 · Brain
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    Thomas O. Krag · John Vissing
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    ABSTRACT: Limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the Fukutin-related protein (FKRP) gene, leading to inadequate glycosylation of α-dystroglycan, an important protein linking the extracellular matrix to the cytoskeleton. We created a mouse model of the common FKRP L276I mutation and a hemizygous FKRP L276I knockout model. We studied histopathology and protein expression in the models at different ages and found that homozygous FKRP L276I mice developed a mild progressive myopathy with increased muscle regeneration and fibrosis starting from 1 year of age. This was likely caused by progressive loss of α-dystroglycan-specific glycosylation, which was decreased by 78% at 20 months. The homozygous FKRP knockout was embryonic lethal, but the hemizygous L276I model resembled the homozygous FKRP L276I model at comparable ages. These models emphasize the importance of FKRP in maintaining proper glycosylation of α-dystroglycan. The mild progression in the homozygous FKRP L276I model resembles that in patients with LGMD2I who are homozygous for the L276I mutation. This animal model could, therefore, be relevant for understanding the pathophysiology of and developing a treatment strategy for the human disorder.
    Preview · Article · Dec 2015 · Journal of Neuropathology and Experimental Neurology
  • Julia Rebecka Dahlqvist · John Vissing
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    ABSTRACT: There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons with muscle wasting due to neuromuscular conditions, however, a common belief has been that physical activity could accelerate degeneration of the diseased muscle and a careful approach to training has therefore been suggested. In this review, we describe the current knowledge about physical training in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide suggestions for future investigations of training in this condition.
    No preview · Article · Nov 2015 · Journal of Molecular Neuroscience
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    ABSTRACT: Background and purpose: Over the last three decades mitochondrial dysfunction has been postulated to be a potential mechanism in migraine pathogenesis. The lifetime prevalence of migraine in persons carrying the 3243A>G mutation in mitochondrial DNA was investigated. Methods: In this cross-sectional study, 57 mDNA 3243A>G mutation carriers between May 2012 and October 2014 were included. As a control group, a population-based cohort from our epidemiological studies on migraine in Danes was used. History of headache and migraine was obtained by telephone interview, based on a validated semi-structured questionnaire, performed by trained physicians. Results: The prevalence of migraine is significantly higher in persons carrying the 3243A>G mutation than in controls (58% vs. 18%; P < 0.001). This applies for both subforms of migraine, migraine without aura (47% vs. 12%; P < 0.001) and migraine with aura (18% vs. 6%; P < 0.001), and in females (58% vs. 24%; P < 0.001) and males (58% vs. 12%; P < 0.001) for any migraine. Conclusions: A high prevalence of migraine in persons with the mDNA 3243A>G mutation was found. This finding suggests a clinical association between a monogenetically inherited disorder of mitochondrial dysfunction and susceptibility to migraine. Mitochondrial DNA aberrations may contribute to the pathogenesis of migraine.
    No preview · Article · Oct 2015 · European Journal of Neurology
  • K. Knak · L. Andersen · N. Witting · J. Vissing

    No preview · Article · Oct 2015 · Neuromuscular Disorders

  • No preview · Article · Oct 2015 · Neuromuscular Disorders

  • No preview · Article · Oct 2015 · Neuromuscular Disorders
  • T. Krag · T. Pinos · T. Nielsen · A. Brull · A. Andreu · J. Vissing

    No preview · Article · Oct 2015 · Neuromuscular Disorders

  • No preview · Article · Oct 2015 · Neuromuscular Disorders
  • K. Heje · G. Andersen · J. Vissing

    No preview · Article · Oct 2015 · Neuromuscular Disorders
  • N. Løkken · G. Hedermann · C. Thomsen · J. Vissing

    No preview · Article · Oct 2015 · Neuromuscular Disorders
  • T. Nielsen · T. Pinos · T. Krag · J. Vissing

    No preview · Article · Oct 2015 · Neuromuscular Disorders
  • L. Andersen · K. Knak · N. Witting · J. Vissing

    No preview · Article · Oct 2015 · Neuromuscular Disorders

  • No preview · Article · Oct 2015 · Neuromuscular Disorders

  • No preview · Article · Oct 2015 · Neuromuscular Disorders

Publication Stats

4k Citations
1,374.17 Total Impact Points

Institutions

  • 2007-2015
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1989-2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States
  • 2007-2014
    • Rigshospitalet
      • Neuromuscular Research Unit
      København, Capital Region, Denmark
  • 2013
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
    • Aarhus University
      Aarhus, Central Jutland, Denmark
  • 2012
    • Children's Heart Center
      Las Vegas, Nevada, United States
  • 2007-2012
    • Copenhagen Trial Unit
      København, Capital Region, Denmark
  • 2011
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • Hospital Universitari de Bellvitge
      l'Hospitalet de Llobregat, Catalonia, Spain
  • 1996-2010
    • National University (California)
      San Diego, California, United States
  • 2009
    • New York Presbyterian Hospital
      New York, New York, United States
  • 2002
    • Rigshospitalet
      København, Capital Region, Denmark
  • 2001
    • University of Texas at Dallas
      Richardson, Texas, United States
    • The John F. Kennedy Institute, Denmark
      Glostrup, Capital Region, Denmark
  • 1994-1995
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark