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A novel diagnostic approach to patients with myoclonus

Nature Reviews Neurology volume 11, pages 687–697 (2015)Cite this article

Subjects

Key Points

  • Myoclonus is characterized by sudden, involuntary jerks, and can be caused by a variety of acquired and genetic factors

  • Clinical neurophysiological tests help to determine the anatomical origin of the myoclonic jerks

  • Recognition of the reversible forms of myoclonus is important for prompt instigation of treatment

  • Next-generation sequencing techniques enable rapid diagnosis in genetic causes of myoclonus

  • Here, we provide a novel eight-step algorithm for myoclonus to aid clinical decision-making and facilitate mechanism-based treatment

Abstract

Myoclonus is a hyperkinetic movement disorder characterized by brief, involuntary muscular jerks. Recognition of myoclonus and determination of the underlying aetiology remains challenging given that both acquired and genetically determined disorders have varied manifestations. The diagnostic work-up in myoclonus is often time-consuming and costly, and a definitive diagnosis is reached in only a minority of patients. On the basis of a systematic literature review up to June 2015, we propose a novel diagnostic eight-step algorithm to help clinicians accurately, efficiently and cost-effectively diagnose myoclonus. The large number of genes implicated in myoclonus and the wide clinical variation of these genetic disorders emphasize the need for novel diagnostic techniques. Therefore, and for the first time, we incorporate next-generation sequencing (NGS) in a diagnostic algorithm for myoclonus. The initial step of the algorithm is to confirm whether the movement disorder phenotype is consistent with, myoclonus, and to define its anatomical subtype. The next steps are aimed at identification of both treatable acquired causes and those genetic causes of myoclonus that require a diagnostic approach other than NGS. Finally, other genetic diseases that could cause myoclonus can be investigated simultaneously by NGS techniques. To facilitate NGS diagnostics, we provide a comprehensive list of genes associated with myoclonus.

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Figure 1: A novel eight-step diagnostic algorithm for myoclonus.

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Acknowledgements

We would like thank Jackie Senior and Kate McIntyre for editing this manuscript.

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Authors and Affiliations

  1. Department of Neurology, University Medical Centre Groningen, PO Box 30.001, Groningen, 9700 RB, Netherlands

    Rodi Zutt, Jan Willem Elting, Oebele F. Brouwer, Deborah A. Sival, Hubertus P. Kremer, Tom J. de Koning & Marina A. Tijssen

  2. Department of Radiology, University Medical Centre Groningen, PO Box 30.001, Groningen, 9700 RB, Netherlands

    Peter Jan van Laar

  3. Department of Genetics, University Medical Centre Groningen, PO Box 30.001, Groningen, 9700 RB, Netherlands

    Tom J. de Koning

  4. Department of Neurology, Ommelander Ziekenhuisgroep, PO Box 30.000, Delfzijl and Winschoten, 9670 RA, Netherlands

    Martje E. van Egmond

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Contributions

R.Z. wrote the article. R.Z., T.J.d.K. and M.A.T. researched data for article and provided substantial contributions to discussion of the content. All authors reviewed and/or edited manuscript before submission. T.J.d.K. and M.A.T. contributed equally to the manuscript.

Corresponding author

Correspondence to Marina A. Tijssen.

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Competing interests

M.E.v.E. received a travel grant from Medtronic in 2014. O.F.B. is a member of an advisory committee for Viropharma (Shire) and presented lectures at sponsored meetings organize by UCB Pharma. T.J.d.K.has received a research grant from Actelion and presented a lecture at a meeting sponsored by Genzyme. M.A.T. has received educational grants from Actelion, Allergan, Ipsen, Medtronic and Merz. The other authors declare no competing interests.

Supplementary information

Supplementary Appendix 1

Full electronic search strategy for a systematic review of causes of myoclonus (DOCX 94 kb)

Supplementary Table 1

Comprehensive overview of genes associated with myoclonus (DOCX 300 kb)

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Zutt, R., van Egmond, M., Elting, J. et al. A novel diagnostic approach to patients with myoclonus. Nat Rev Neurol 11, 687–697 (2015). https://doi.org/10.1038/nrneurol.2015.198

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