Background: Transcranial sonography (TCS) area of hyperechogenicity in the substantia nigra (aSN) is increased in idiopathic and genetic Parkinson's disease (PD). Methods: We performed TCS in 34 LRRK2 G2019S mutation carriers manifesting PD, 24 non-manifesting mutation carriers, and 28 idiopathic PD patients and compared them with 40 healthy controls (total, n 5 126). Results: Compared with the controls (mean 0.15 cm 2 ), the aSN values in all other groups were increased. The mean aSN was 0.23 cm 2 in nonmanifesting mutation carriers (P 5 .015), 0.34 cm 2 in idiopathic PD patients (P < .0001), 0.32 cm 2 in LRRK2-associated PD patients (P < .0001), and 0.33 cm 2 in the overall PD group (P < .0001). LRRK2-associated PD patients had a higher aSN than did nonmanifesting carriers (P 5 .011), but there was no significant difference in aSN between patients with idiopathic and LRRK2-associated PD (P 5.439).
Conclusions: Our results suggest that SN pathoanatomical alterations may not be substantially different between idiopathic and LRRK2-associated PD. The findings in the nonmanifesting mutation carriers suggest the presence of intermediate nigrostriatal pathology consistent with the age-dependent reduced penetrance of this mutation. V