Clinical and imaging markers in premotor LRRK2 G2019S mutation carriers.

Background: Substantia nigra hyperechogenicity (SN+) has been proposed as a risk marker of Parkinson's disease (PD). Asymptomatic LRRK2 mutation carriers (aLRRK2+), at high risk for developing PD, provide an opportunity for the study of preclinical biomarkers.

Objective: To assess SN echogenicity and other echographic features in LRRK2 G2019S carriers and their clinical and imaging correlates.

Methods: Transcranial sonography was performed in 26 LRRK2 G2019S PD patients, 50 first-degree relatives, 31 idiopathic PD (IPD) patients and 26 controls. SN echogenicity and other echographic features were assessed in all study subjects. Dopamine transporter imaging (DAT-SPECT) was performed in 29 first-degree relatives.

Results: 75% of the LRRK2-PD and 87.5% of the IPD showed SN+ (p = 0.087). aLRRK2+ had a higher frequency of SN+ than non carriers (58.3% vs. 25%, p = 0.039) and controls (58.3% vs. 12.5%; p = 0.002) and had a larger area of SN echogenicity than non carriers (p = 0.030) and controls (p < 0.001). The width of the third ventricle was significantly lower in LRRK2-PD than in IPD (1.9 mm [1.38; 2.75] vs. 3.0 mm [2.3; 5.3]; p = 0.003). Four out of 5 (80%) of the aLRRK2+ with an abnormal DAT-SPECT and four of the 5 (80%) of those with REM sleep behaviour disorder (RBD) had SN+.

Conclusions: SN+ is very frequent in LRRK2-PD and aLRRK2+. Most aLRRK2 with possible surrogate markers of PD such as abnormal DAT-SPECT or RBD, also had SN+, which supports that this echofeature might be a marker of PD in these asymptomatic population.