OBJECTIVE: To ascertain in a cross-sectional study whether substantia nigra (SN) echogenicity, olfaction, and dopamine transporter (DaT)-SPECT are reliable premotor biomarkers in a cohort of asymptomatic carriers of the LRRK2 G2019S mutation (AsG2019S+). METHODS: These biomarkers were evaluated in 49 AsG2019S+ patients, and we also studied olfaction and SN echogenicity in 29 patients with G2019S-associated Parkinson disease (PD-G2019S), 47 relatives who were noncarriers of the LRRK2 G2019S mutation (AsG2019S-), 50 patients with idiopathic Parkinson disease (iPD), and 50 community controls. RESULTS: Eighty-five percent of unaffected mutation carriers (AsG2019S+) showed pathologic SN hyperechogenicity, with a similar proportion observed among both PD-G2019S and iPD cases, and 41% of AsG2019S- also showing increased SN echogenicity. The proportion of hyposmic individuals was not statistically different in patients with PD-G2019S (50%) and iPD (82%), but hyposmia was significantly less common in both AsG2019S+ (26%) and AsG2019S- (28%). In AsG2019S+ cases, reduced striatal uptake in DaT-SPECT was observed in 43.7%. CONCLUSIONS: Independently of age at examination, the most frequently altered premotor biomarker in LRRK2 G2019S-associated PD was SN hyperechogenicity, whereas abnormal DaT-SPECT predominated in older, unaffected mutation carriers.
OBJECTIVE: To ascertain in a cross-sectional study whether substantia nigra (SN) echogenicity, olfaction, and dopamine transporter (DaT)-SPECT are reliable premotor biomarkers in a cohort of asymptomatic carriers of the LRRK2G2019S mutation (AsG2019S+). METHODS: These biomarkers were evaluated in 49 AsG2019S+ patients, and we also studied olfaction and SN echogenicity in 29 patients with G2019S-associated Parkinson disease (PD-G2019S), 47 relatives who were noncarriers of the LRRK2G2019S mutation (AsG2019S-), 50 patients with idiopathic Parkinson disease (iPD), and 50 community controls. RESULTS: Eighty-five percent of unaffected mutation carriers (AsG2019S+) showed pathologic SN hyperechogenicity, with a similar proportion observed among both PD-G2019S and iPD cases, and 41% of AsG2019S- also showing increased SN echogenicity. The proportion of hyposmic individuals was not statistically different in patients with PD-G2019S (50%) and iPD (82%), but hyposmia was significantly less common in both AsG2019S+ (26%) and AsG2019S- (28%). In AsG2019S+ cases, reduced striatal uptake in DaT-SPECT was observed in 43.7%. CONCLUSIONS: Independently of age at examination, the most frequently altered premotor biomarker in LRRK2G2019S-associated PD was SN hyperechogenicity, whereas abnormal DaT-SPECT predominated in older, unaffected mutation carriers.
Authors: Danna Jennings; Andrew Siderowf; Matthew Stern; John Seibyl; Shirley Eberly; David Oakes; Kenneth Marek Journal: JAMA Neurol Date: 2017-08-01 Impact factor: 18.302
Authors: Danna Jennings; Andrew Siderowf; Matthew Stern; John Seibyl; Shirley Eberly; David Oakes; Kenneth Marek Journal: Neurology Date: 2014-10-08 Impact factor: 9.910
Authors: Shu-Ying Liu; Daryl J Wile; Jessie Fanglu Fu; Jason Valerio; Elham Shahinfard; Siobhan McCormick; Rostom Mabrouk; Nasim Vafai; Jess McKenzie; Nicole Neilson; Alexandra Perez-Soriano; Julieta E Arena; Mariya Cherkasova; Piu Chan; Jing Zhang; Cyrus P Zabetian; Jan O Aasly; Zbigniew K Wszolek; Martin J McKeown; Michael J Adam; Thomas J Ruth; Michael Schulzer; Vesna Sossi; A Jon Stoessl Journal: Lancet Neurol Date: 2018-02-16 Impact factor: 44.182