title: Clinical and imaging markers in premotor LRRK2 G2019S mutation carriers.
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.
authors: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Catalonia, Spain.
authors: Dolores
authors: D
authors: Vilas
authors: Neurology Service, Hospital Universitari Germans Trias I Pujol, Badalona, Spain.
authors: Lourdes
authors: L
authors: Ispierto
authors: Neurology Service, Hospital Universitari Germans Trias I Pujol, Badalona, Spain.
authors: Ramiro
authors: R
authors: Álvarez
authors: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Catalonia, Spain.
authors: Claustre
authors: C
authors: Pont-Sunyer
authors: 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.
authors: María José
authors: MJ
authors: Martí
authors: 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.
authors: Francesc
authors: F
authors: Valldeoriola
authors: 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.
authors: Yaroslau
authors: Y
authors: Compta
authors: Neurology Service, Hospital Universitari Vall D'Hebron, Barcelona, Catalonia, Spain.
authors: Oriol
authors: O
authors: de Fabregues
authors: Neurology Service, Hospital Universitari Vall D'Hebron, Barcelona, Catalonia, Spain.
authors: Jorge
authors: J
authors: Hernández-Vara
authors: Neurology Service, Hospital Del Mar, Barcelona, Catalonia, Spain.
authors: Víctor
authors: V
authors: Puente
authors: Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Catalonia, Spain.
authors: Matilde
authors: M
authors: Calopa
authors: Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Catalonia, Spain.
authors: Serge
authors: S
authors: Jaumà
authors: Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Catalonia, Spain.
authors: Jaume
authors: J
authors: Campdelacreu
authors: Neurology Service, Hospital Universitari Mutua de Terrasa, Barcelona, Catalonia, Spain.
authors: Miquel
authors: M
authors: Aguilar
authors: Neurology Service, Hospital Universitari Mutua de Terrasa, Barcelona, Catalonia, Spain.
authors: Pilar
authors: P
authors: Quílez
authors: Hospital Mateu Orfila, Maó, Menorca, Spain.
authors: Pilar
authors: P
authors: Casquero
authors: Nuclear Medicine Service, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain.
authors: Francisco
authors: F
authors: Lomeña
authors: Biostatistics and Data Management Core Facility, IDIBAPS, (Hospital Clinic), Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain.
authors: José
authors: J
authors: Ríos
authors: 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.
authors: Eduardo
authors: E
authors: Tolosa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013378:Substantia Nigra / Q000000981:diagnostic imaging*; D015899:Tomography, Emission-Computed, Single-Photon; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Genetic; LRRK2; Parkinson; Substantia nigra; Transcranial ultrasound