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Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti-AChR antibodies

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An Erratum to this article was published on 11 January 2011

Abstract

Patients with myasthenia gravis (MG) with antibodies to muscle-specific receptor tyrosine kinase (MuSK) differ from acetylcholine receptor (AChR)-positive MG patients, as they frequently present with severe oculobulbar muscle weakness or with neck, shoulder, and respiratory muscle involvement. The neuromuscular junction (NMJ) has been confirmed to be the main target of both AChR- and MuSK-MG. However, histopathological investigation disclosed that muscle fiber atrophy was prevalent in AChR-MG, whereas mild myopathic changes and mitochondrial abnormalities were more frequently observed in MuSK-MG. As the pathogenetic mechanism in MuSK-MG remains unclear, this study investigated the submicroscopic pattern of muscle histopathology to establish a possible correlation between clinical involvement and subcellular morphological findings. Muscle biopsies from seven MuSK-MG patients and from seven patients with AChR-MG were analyzed by transmission electron microscopy. Myopathic and mitochondrial abnormalities were more prominent in MuSK-MG and show giant, swollen, and degenerated mitochondria with fragmented cristae. The most common changes in AChR-MG muscles were fiber atrophy, myofibrillar disarray, and Z-line streaming, consistent with mild neurogenic abnormalities. A different pathogenetic mechanism is emerging in MuSK-MG compared to AChR-MG. Mitochondrial abnormalities seem to be more prominent in MuSK-MG, whereas neurogenic atrophy is observed in AChR-MG.

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Acknowledgments

This paper has been partly supported by a Fondazione Carisbo and by Bologna University EF 2008 grants. The funding sources had no involvement in study design, collection, analysis, or interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. The authors acknowledge Telethon Italy for their support (project # GTB07001 to C.A.).

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Clinical Department of Radiological Histopathological Sciences, “Alma Mater Studiorum” University of Bologna, Via Massarenti, 9, 40137, Bologna, Italy

    Giovanna Cenacchi & Papa Valentina

  2. Department Neurosciences, University of Padua, Padua, Italy

    Fanin Marina, Pegoraro Elena & Angelini Corrado

Authors
  1. Giovanna Cenacchi
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  2. Papa Valentina
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  3. Fanin Marina
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  4. Pegoraro Elena
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  5. Angelini Corrado
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Correspondence to Giovanna Cenacchi.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00415-010-5881-0

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Cenacchi, G., Valentina, P., Marina, F. et al. Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti-AChR antibodies. J Neurol 258, 746–752 (2011). https://doi.org/10.1007/s00415-010-5823-x

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  • DOI: https://doi.org/10.1007/s00415-010-5823-x

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