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.

Automated summary

The diagnostic approach for adulthood parkinsonism is challenging when atypical features make it difficult to classify into Parkinson's disease or atypical parkinsonian syndromes (APS). This study retrospectively analyzed patients with a diagnosis of atypical APS and complex parkinsonism, and found distinctive non-neurodegenerative etiologies causing atypical and complex parkinsonism. Accurate clinical identification and distinction between neurodegenerative and non-neurodegenerative parkinsonism etiologies will allow for refining clinical trials. Rating: 8/10.