The etiopathogenetic and pathophysiological spectrum of parkinsonism

Parkinsonism is a syndrome characterized by bradykinesia, rigidity, and tremor. Parkinsonism is a common manifestation of Parkinson's disease and other neurodegenerative diseases referred to as atypical parkinsonism. However, a growing body of clinical and scientific evidence indicates that parkinsonism may be part of the phenomenological spectrum of various neurological conditions to a greater degree than expected by chance. These include neurodegenerative conditions not traditionally classified as movement disorders, e.g., dementia and motor neuron diseases. In addition, parkinsonism may characterize a wide range of central nervous system diseases, e.g., autoimmune diseases, infectious diseases, cerebrospinal fluid disorders (e.g., normal pressure hydrocephalus), cerebrovascular diseases, and other conditions. Several pathophysiological mechanisms have been identified in Parkinson's disease and atypical parkinsonism. Conversely, it is not entirely clear to what extent the same mechanisms and key brain areas are also involved in parkinsonism due to a broader etiopathogenetic spectrum. We aimed to provide a comprehensive and up-to-date overview of the various etiopathogenetic and pathophysiological mechanisms of parkinsonism in a wide spectrum of neurological conditions, with a particular focus on the role of the basal ganglia involvement. The paper also highlights potential implications in the diagnostic approach and therapeutic management of patients. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.