Redefinition of Atypical Parkinsonian Syndromes

The term “atypical parkinsonian syndrome” is traditionally used for several neurodegenerative diseases, including multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). Their defining commonality consists in their akinetic-rigid extrapyramidal movement disorder. In contrast to idiopathic Parkinson’s disease (PD), the atypical parkinsonian syndromes often have additional clinical characteristics, such as poor response to dopaminergic therapy, more rapid disease progression, and poorer prognosis [1]. MSA, DLB and PSP are still predominantly considered as clinico-pathologically coherent disease entities. However, this concept has already been abandoned in CBD, which is now considered a purely neuropathologically defined disease entity; the clinically defined corticobasal syndrome (CBS) can be traced back only to a relatively small extent (about 25 %) to the neuropathological diagnosis of CBD. To a considerable extent, CBS is also caused by PSP pathology or Alzheimer’s disease (AD) pathology. Conversely, the neuropathological diagnosis of CBD frequently presents with clinical syndromes other than CBS. In this regard, the classification system of CBS/CBD is already more advanced than that of the other atypical parkinsonian syndromes, since a clear distinction has been made in the nomenclature between clinical syndrome (CBS) and the underlying neuropathology (CBD). For historical reasons, the classification of atypical parkinsonian syndromes has been made in accordance with their clinical appearance (▶Fig. 1). The use of such a clinically-guided classification system stands to reason, because the constellation of clinical signs and symptoms has always been the physician’s first basis for the generation of a diagnosis. Such a clinical-descriptive categorization allowed initial observations regarding the typical symptoms, demography and epidemiology, as well as the first theories on the cause of the diseases. Precise clinical characterization generally is an essential prerequisite for an etiological and pathogenetic understanding of a disease. The latter should explain the causes and mechanisms of the disease and help derive therapeutic approaches from the pathophysiological processes. According to the traditional disease concept, atypical parkinsonian syndromes defined a disease clinically. The purpose Redefinition of Atypical Parkinsonian Syndromes