Dolores Vilas1, Lourdes Ispierto2, Ramiro Álvarez2, Claustre Pont-Sunyer1, María José Martí3, Francesc Valldeoriola3, Yaroslau Compta3, Oriol de Fabregues4, Jorge Hernández-Vara4, Víctor Puente5, Matilde Calopa6, Serge Jaumà6, Jaume Campdelacreu6, Miquel Aguilar7, Pilar Quílez7, Pilar Casquero8, Francisco Lomeña9, José Ríos10, Eduardo Tolosa11. 1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Catalonia, Spain. 2. Neurology Service, Hospital Universitari Germans Trias I Pujol, Badalona, Spain. 3. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Catalonia, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain. 4. Neurology Service, Hospital Universitari Vall D'Hebron, Barcelona, Catalonia, Spain. 5. Neurology Service, Hospital Del Mar, Barcelona, Catalonia, Spain. 6. Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Catalonia, Spain. 7. Neurology Service, Hospital Universitari Mutua de Terrasa, Barcelona, Catalonia, Spain. 8. Hospital Mateu Orfila, Maó, Menorca, Spain. 9. Nuclear Medicine Service, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain. 10. Biostatistics and Data Management Core Facility, IDIBAPS, (Hospital Clinic), Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain. 11. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Catalonia, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: etolosa@clinic.ub.es.
Abstract
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.
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 LRRK2G2019S carriers and their clinical and imaging correlates. METHODS: Transcranial sonography was performed in 26 LRRK2G2019SPDpatients, 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.
Authors: Tanya Simuni; Liz Uribe; Hyunkeun Ryan Cho; Chelsea Caspell-Garcia; Christopher S Coffey; Andrew Siderowf; John Q Trojanowski; Leslie M Shaw; John Seibyl; Andrew Singleton; Arthur W Toga; Doug Galasko; Tatiana Foroud; Duygu Tosun; Kathleen Poston; Daniel Weintraub; Brit Mollenhauer; Caroline M Tanner; Karl Kieburtz; Lana M Chahine; Alyssa Reimer; Samantha J Hutten; Susan Bressman; Kenneth Marek Journal: Lancet Neurol Date: 2019-10-31 Impact factor: 44.182
Authors: Asha Kishore; Ashwin Ashok Kumar Sreelatha; Marc Sturm; Felix von-Zweydorf; Lasse Pihlstrøm; Francesco Raimondi; Rob Russell; Peter Lichtner; Moinak Banerjee; Syam Krishnan; Roopa Rajan; Divya Kalikavil Puthenveedu; Sun Ju Chung; Peter Bauer; Olaf Riess; Christian Johannes Gloeckner; Rejko Kruger; Thomas Gasser; Manu Sharma Journal: Mov Disord Date: 2018-11-28 Impact factor: 10.338
Authors: Mattia Volta; Dayne A Beccano-Kelly; Sarah A Paschall; Stefano Cataldi; Sarah E MacIsaac; Matthew J Farrer; Austen J Milnerwood; Naila Kuhlmann; Chelsie A Kadgien; Igor Tatarnikov; Jesse Fox; Jaskaran Khinda; Emma Mitchell; Sabrina Bergeron; Heather Melrose Journal: Elife Date: 2017-09-20 Impact factor: 8.140
Authors: Amy K Reeve; John P Grady; Eve M Cosgrave; Emma Bennison; Chun Chen; Philippa D Hepplewhite; Christopher M Morris Journal: NPJ Parkinsons Dis Date: 2018-03-26