alpha-synuclein and Cerebellar-Diseases

Brains from patients with Parkinson disease or dementia with Lewy bodies show aggregation of alpha-synuclein in precerebellar brainstem structures. Furthermore, patients exhibit resting tremor, unstable gait, and impaired balance, which may be associated with cerebellar dysfunction. Therefore, we screened the cerebella of 12 patients with alpha-synucleinopathies for neuropathological changes. Cerebellar nuclei and neighboring white matter displayed numerous aggregates, whereas lobules were mildly affected. Cerebellar aggregation pathology may suggest a prionlike spread originating from affected precerebellar structures, and the high homogeneity between patients with dementia with Lewy bodies and Parkinson disease shows that both diseases likely belong to the same neuropathological spectrum. Ann Neurol 2017;81:898-903.

Topics: alpha-Synuclein; Cerebellar Diseases; Humans; Lewy Body Disease; Parkinson Disease

Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) involve cytoplasmic deposition of α-synuclein and are considered to be synucleinopathies. Approximately 40% of patients with PD, most patients with MSA, and all patients with PAF have neurogenic orthostatic hypotension (OH). This study compared long-term survival in these synucleinopathies.. In this prospective cohort study, survival data were obtained for 97.6% of 206 referred patients evaluated between 1994 and 2014 (47 PD + OH, 54 PD no OH, 15 cerebellar MSA [MSA-C], 57 parkinsonian MSA [MSA-P], 28 PAF). Individual diagnoses were confirmed by clinical criteria and results of pharmacologic, neurochemical, and neuroimaging tests of sympathetic noradrenergic innervation. The Cox proportional hazard model was used to calculate hazard ratios (HRs) from symptom onset and from time of evaluation to death.. Patients with MSA-C or MSA-P had shorter survival from symptom onset than did patients with PD + OH (age- and sex-adjusted HR = 6.1, 5.6; p < 0.0001 each), PAF (HR = 10.8, 9.9; p < 0.0001 each) or PD no OH (HR = 14.9, 13.6; p < 0.0001 each). Among parkinsonian patients who died, median times from motor onset to death were 7.5 years in MSA-P, 11.6 years in PD + OH, and 15.8 years in PD no OH. Probabilities of survival for 10 years from onset of relevant symptoms were 0.39 in MSA-C, 0.33 in MSA-P, 0.74 in PD + OH, 0.87 in PAF, and 0.93 in PD no OH.. In synucleinopathies, survival depends on the particular disease, with the risk of death greater in MSA-P than in PD + OH and in PD + OH than in PD no OH.

Topics: Aged; alpha-Synuclein; Brain; Cerebellar Diseases; Cohort Studies; Dihydroxyphenylalanine; Female; Fluorine Radioisotopes; Humans; Longitudinal Studies; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Proportional Hazards Models; Prospective Studies; Pure Autonomic Failure; Radionuclide Imaging

Topics: alpha-Synuclein; Basal Ganglia; Cerebellar Diseases; Cerebellum; Dopamine; Female; Gait Disorders, Neurologic; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Middle Aged; Multiple System Atrophy; Receptors, Dopamine; Tomography, Emission-Computed, Single-Photon; Ubiquitin

Topics: Adult; alpha-Synuclein; Ataxins; Cerebellar Diseases; Fluorescent Antibody Technique; Humans; Inclusion Bodies; Male; Microscopy, Confocal; Multiple System Atrophy; Nerve Tissue Proteins; Neuroglia; Synucleins