ABSTRACT
BACKGROUND: In Parkinson's disease (PD), alpha-synuclein (AS) aggregates occur frequently in peripheral autonomic nervous system (pANS). Their presence in asymptomatic subjects suggests incidental Lewy-body disease (iLBD) that is thought to reflect pre-clinical PD. Cardiac involvement has been detected in post-mortem studies in both, PD and also in iLBD. In vivo documentation of cardiac AS pathology is lacking. OBJECTIVE: To prospectively assess the presence of AS aggregates in epicardial fat tissue from living subjects without parkinsonism undergoing elective cardiac surgery. MATERIAL AND METHODS: Epicardial fat tissue obtained during cardiac surgery from 91 subjects was studied by histology and immunohistochemistry. Areas more likely to contain pANS elements were selected. PD-related motor and non-motor symptoms (NMS) were assessed immediately before or after surgery. RESULTS: Small autonomic nerves, ganglia and/or tyrosine-hydroxylase positive fibres were identified in epicardial fat in each of the 91 subjects (62 male/29 female, mean age 67 years). AS aggregates were detected in 7 subjects (7.7%), and were more frequent in those aged above 70 years. In AS-positive subjects constipation and acting dreams were significantly more frequent than in the AS-negative ones. CONCLUSION: AS aggregates occur in epicardial pANS in subjects without parkinsonism, suggesting the diagnosis of iLBD. The presence in some of these subjects of non-motor symptoms such as acting dreams and constipation known to occur in premotor PD supports this interpretation. Adequate follow-up of the subjects in this study will indicate the time, if any, to progression to motor PD.
Subject(s)
Adipose Tissue/pathology , Autonomic Nervous System/pathology , Lewy Body Disease/pathology , Tyrosine 3-Monooxygenase/metabolism , alpha-Synuclein/metabolism , Aged , Aged, 80 and over , Female , Heart/innervation , Humans , Lewy Body Disease/metabolism , Male , Middle Aged , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/pathology , Prospective StudiesABSTRACT
Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ((123)I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([(123)I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [(123)I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [(123)I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.
