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Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation.
Mov Disord 2013; 28(12):1683-90MD

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.

Authors+Show Affiliations

Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; School of Health-Related Professions, Ben Gurion University, Beer Sheba, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24123150

Citation

Mirelman, Anat, et al. "Fall Risk and Gait in Parkinson's Disease: the Role of the LRRK2 G2019S Mutation." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 28, no. 12, 2013, pp. 1683-90.
Mirelman A, Heman T, Yasinovsky K, et al. Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation. Mov Disord. 2013;28(12):1683-90.
Mirelman, A., Heman, T., Yasinovsky, K., Thaler, A., Gurevich, T., Marder, K., ... Hausdorff, J. M. (2013). Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation. Movement Disorders : Official Journal of the Movement Disorder Society, 28(12), pp. 1683-90. doi:10.1002/mds.25587.
Mirelman A, et al. Fall Risk and Gait in Parkinson's Disease: the Role of the LRRK2 G2019S Mutation. Mov Disord. 2013;28(12):1683-90. PubMed PMID: 24123150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation. AU - Mirelman,Anat, AU - Heman,Talia, AU - Yasinovsky,Kira, AU - Thaler,Avner, AU - Gurevich,Tanya, AU - Marder,Karen, AU - Bressman,Susan, AU - Bar-Shira,Anat, AU - Orr-Urtreger,Avi, AU - Giladi,Nir, AU - Hausdorff,Jeffrey M, AU - ,, Y1 - 2013/10/07/ PY - 2012/12/09/received PY - 2013/05/18/revised PY - 2013/06/04/accepted PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2014/6/21/medline KW - G2019S KW - LRRK2 KW - Parkinson's disease KW - falls KW - gait SP - 1683 EP - 90 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 28 IS - 12 N2 - 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. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/24123150/Fall_risk_and_gait_in_Parkinson's_disease:_the_role_of_the_LRRK2_G2019S_mutation_ L2 - https://doi.org/10.1002/mds.25587 DB - PRIME DP - Unbound Medicine ER -