title: Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected].
abstract: BACKGROUND
  Patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) may develop neurodegenerative conditions associated with substantia nigra dysfunction such as Parkinson's disease. In patients with Parkinson's disease, ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (¹²³I-FP-CIT) SPECT detects striatal dopamine dysfunction resulting from nigral pathology whereas transcranial sonography (TCS) shows increased substantia nigra echogenic size, even before parkinsonism is clinically evident. We postulated that these neuroimaging changes could occur in a proportion of IRBD individuals who might then be at increased risk for development of a neurodegenerative disorder associated with substantia nigra dysfunction.
  
  
  METHODS
  In our prospective study, we identified patients with IRBD from individuals referred to our sleep disorders centre in Barcelona, Spain. At baseline, we assessed dopamine transporter [corrected] uptake by use of ¹²³I-FP-CIT SPECT, and estimated echogenicity of the substantia nigra by use of TCS. After a follow-up of 2·5 years, participants were clinically assessed to establish whether they had developed neurodegenerative syndromes. Data were compared with those of matched healthy controls.
  
  
  RESULTS
  43 individuals with IRBD agreed to participate in the study. We found reduced ¹²³I-FP-CIT binding in the striatum (p=0·045) in 17 (40%) of 43 participants compared with 18 controls, and substantia nigra hyperechogenicity in 14 (36%) of 39 participants with IRBD, compared with 16 (11%) of 149 controls (p=0·0002). Tracer uptake reduction was more pronounced in the putamen than it was in the caudate nucleus. 27 (63%) participants had reduced ¹²³I-FP-CIT binding or substantia nigra hyperechogenicity at baseline. Eight (30%) of these participants developed a neurodegenerative disorder (five Parkinson's disease, two dementia with Lewy bodies, and one multiple system atrophy). Individuals with normal neuroimaging results remained disease-free. Sensitivity of combined ¹²³I-FP-CIT SPECT and TCS to predict conversion to synucleinopathy after 2·5 years was 100% and specificity was 55%.
  
  
  CONCLUSIONS
  In patients with IRBD, ¹²³I-FP-CIT SPECT and TCS can detect subclinical changes much the same as those typically seen in patients with early Parkinson's disease. Decreased striatal ¹²³I-FP-CIT binding and substantia nigra hyperechogenicity might be useful markers to identify individuals at increased risk for development of synucleinopathies.
  
  
  BACKGROUND
  None.
authors.affiliation: Department of Neurology, University Hospital Clinic, Networked Biomedical Research Centre for Neurodegenerative Diseases, The August Pi i Sunyer Biomedical Research Institute, Spain. airanzo@clinic.ub.es
authors.forename: Alex
authors.initials: A
authors.lastname: Iranzo
authors.forename: Francisco
authors.initials: F
authors.lastname: Lomeña
authors.forename: Heike
authors.initials: H
authors.lastname: Stockner
authors.forename: Francesc
authors.initials: F
authors.lastname: Valldeoriola
authors.forename: Isabel
authors.initials: I
authors.lastname: Vilaseca
authors.forename: Manel
authors.initials: M
authors.lastname: Salamero
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Monica
authors.initials: M
authors.lastname: Serradell
authors.forename: Joan
authors.initials: J
authors.lastname: Duch
authors.forename: Javier
authors.initials: J
authors.lastname: Pavía
authors.forename: Judith
authors.initials: J
authors.lastname: Gallego
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.forename: Eduard
authors.initials: E
authors.lastname: Tolosa
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Joan
authors.initials: J
authors.lastname: Santamaria
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011485:Protein Binding / Q000502:physiology; D020187:REM Sleep Behavior Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D012307:Risk Factors; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D051843:Synucleins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D051843:Synucleins