Objective: To assess whether harboring a LRRK2 G2019S mutation is associated with abnormalities in spiral drawing, including in mutation carriers with Parkinson Disease (PD) as well as those without PD (non-manifesting carriers (NMC)).

Background: Digitized spiral drawing is an objective and quantitative task that correlates with PD severity and distinguishes PD from controls. Such a motor marker may be useful in several ways: in tracking progression of disease; in detection of motor abnormalities that are a long-standing endophenotype of harboring a mutation such as G2019S; and/or as an indicator of early objective motor feature of pre-clinical disease.

Methods: Subjects: 72 G2019S mutation PD (LRRK2 PD), 166 non-G2019S PD (IPD), 93 G2019S mutation non-PD (NMC) and 92 non-G2019S, non-PD controls (controls) from three sites completed digitized spiral drawing using methods previously described¹. Linear mixed models were applied to assess group differences in spiral indices for both the dominant and non-dominant hand, adjusting for age, sex, handedness, and site. Indices included overall degree of severity (DoS), irregularity and irregular shape (1stZC and 2ndSm), and loop-to-loop variability (SWVI).

Results: IPD and LRRK2 PD were older than NMC and controls, while controls were older than NMC (all p<0.01), and LRRK2 PD had longer PD duration than IPD (p<0.01). Compared with IPD, LRRK2 PD had less irregularity (1stZC) in both hands, but greater SWVI (all p<0.01) in the dominant hand, and lower DoS in the non-dominant hand (p<0.03). Compared to controls, NMC had higher DoS (p<0.01) and greater SWVI (p=0.012) in the dominant hand and greater irregularity (2ndSm, p=0.036) in the non-dominant hand. Dominant and non-dominant DoS and SWVI were greater in LRRK2 PD compared to controls (both p<0.01).

Conclusions: As expected, spirals are abnormal in LRRK2 PD compared with controls. LRRK2 PD spirals differed from IPD in showing greater spiral width variability but less irregularity. Of interest, NMC also had greater spiral variability compared to controls, although, it was less than LRRK2 PD. NMC also demonstrated greater overall severity compared with controls. This suggests that spiral variability may be a feature that precedes frank parkinsonism in IPD, and parallels arm swing variability during dual tasks reported in NMC².  Longitudinal studies will help demonstrate whether this is a marker on the path to PD, or a compensatory endophenotype in LRRK2 PD.

References: ¹San Luciano M, Wang C, Ortega RA, Yu Q, Boschung S, Soto-Valencia J, et al. (2016) Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson’s Disease. PLoS ONE 11(10): e0162799. doi:10.1371/journal.pone.0162799

²Mirelman A, Bernad-Elazari H, Thaler A, et al. Arm Swing as a Potential New Prodromal Marker of Parkinson’s Disease. Movement disorders : official journal of the Movement Disorder Society. 2016;31(10):1527-1534. doi:10.1002/mds.26720.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/spiral-analysis-is-a-promising-biomarker-in-lrrk2-g2019s-carriers/