Neuropathology of Atypical Parkinsonian Disorders

Although the clinical syndrome of parkinsonism (rigidity, bradykinesia, and tremor) is most often owing to idiopathic Parkinson’s disease (PD), it may also be associated with a variety of other underlying pathologies (Table 1) (1–3). Each of these other pathological conditions tends to have a characteristic clinical phenotype, however atypical cases are increasingly recognized (4–8). Moreover, some patients with PD have additional clinical features such as dementia, autonomic dysfunction, or gastrointestinal dysmotility (9–13). As a result, the accurate diagnosis of a patient with parkinsonism, and especially those with atypical or additional clinical features, ultimately depends on neuropathological examination. This chapter will review the pathological changes that characterize those conditions that may present with or have parkinsonism as a major feature, either in isolation or combined with other clinical manifestations. Although the focus of this text and chapter are the atypical causes of parkinsonism, a description of the pathological features of typical PD is included for comparison. Most of the conditions that cause parkinsonism have damage of the striatonigral system as the common anatomicopathological substrate. Some have additional neuropathology, which is more disease specific, such as the presence of characteristic cellular inclusions in many of the idiopathic neurodegenerative disorders (Table 2). Others, such as many toxic and metabolic conditions, show only nonspecific chronic degeneration with neuronal loss and reactive gliosis. In this chapter, greater discussion will be devoted to those disease entities that more commonly cause parkinsonism and have distinctive pathology, whereas conditions that rarely cause parkinsonism and those with nonspecific pathology will receive less attention.