Diagnosis across a cohort of "atypical" atypical and complex parkinsonism

Introduction: The diagnostic approach for adulthood parkinsonism can be challenging when atypical features hamper its classification in one of the two main parkinsonian groups: Parkinson's disease or atypical parkin-sonian syndromes (APS). Atypical features are usually associated with non-sporadic neurodegenerative causes.Methods: Retrospective analysis of patients with a working clinical diagnosis of "atypical" APS and complex parkinsonism. "Atypical" APS were classified according to the diagnostic research criteria and the "4-step diagnostic approach" (Stamelou et al. 2013). When not indicated, the final aetiological diagnosis was prospec-tively assessed. Brain MRI of progressive supranuclear palsy (PSP) look-alikes was reviewed by a neuroradiologist.Results: Among 18 patients enrolled, ten were assigned to the "atypical" APS and eight to the complex parkin-sonism group. In the "atypical" APS group, nine patients had PSP and one had corticobasal degeneration. In the PSP group the median magnetic resonance parkinsonism index was 17.1. A final aetiological diagnosis was established for 11 patients, four from the complex parkinsonism (L-2-hidroxiglutaric aciduria and DiGeorge syndrome) and seven from the "atypical" APS (Perry syndrome, postencephalitic PSP, vascular PSP, and MTP-AT6 mitochondrial disease) group.Conclusions: In this study, the identification of atypical APS features, as proposed in the "4-step diagnostic approach", successfully guided the investigation of alternative diagnoses. Distinctive non-neurodegenerative etiologies causing "atypical" atypical and complex parkinsonism were uncovered, including acquired (post -en-cephalitis and vascular) and genetic (MTP-AT6 mitochondrial disease mimicking PSP, described for the first time) ones. In the future, accurate clinical identification and distinction between neurodegenerative and non-neurodegenerative parkinsonism etiologies will allow for refining clinical trials.