Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation

Authors

  • Anat Mirelman PhD,

    Corresponding author
    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
    2. School of Health-Related Professions, Ben Gurion University, Beer Sheba, Israel
    • Correspondence to: Dr. Anat Mirelman, Laboratory for Gait Analysis and Neurodynamics, Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel; anatmi@tasmc.health.gov.il

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  • Talia Heman MsPT,

    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
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  • Kira Yasinovsky BS,

    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
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  • Avner Thaler MD,

    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
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  • Tanya Gurevich MD,

    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
    2. Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Karen Marder MD,

    1. Columbia University, College of Physicians and Surgeons, New York, New York, USA
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  • Susan Bressman MD,

    1. Department of Movement Disorders, Beth Israel Medical Center, New York, New York, USA
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  • Anat Bar-Shira PhD,

    1. Genetics Institute, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel
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  • Avi Orr-Urtreger MD, PhD,

    1. Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    2. Genetics Institute, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel
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  • Nir Giladi MD,

    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
    2. Department of Neurology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Jeffrey M. Hausdorff PhD,

    1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
    2. Department of Physical Therapy, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    3. Harvard Medical School, Boston, Massachusetts, USA
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  • on behalf of the LRRK2 Ashkenazi Jewish Consortium


  • Funding agencies: This research was supported by the Tel Aviv Sourasky Medical Center Grant of Excellence and by grants from the Khan Foundation, the Israel Science Foundation Heritage Legacy, and the Michael J. Fox Foundation for Parkinson's Research. The funding sources had no involvement in the design, interpretation, or writing of this article.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine-rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non-carrier patients with PD to better understand the genotype-phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non-carriers were studied. An accelerometer quantified gait under three walking conditions: usual-walking, dual-tasking, and fast-walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub-types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural-instability-gait-difficulty (PIGD) sub-type compared to only 17% of the PD non-carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub-type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society

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