Historical underpinnings of Parkinson's disease nosography

Abstract

The current definition of Parkinson's disease (PD) is based on clinical and pathological criteria, which have changed many times since their identification in 1817. Indeed, the characterization of PD motor signs (in chronological order: resting tremor, festination, rigidity, akinesia) took more than a century. Psychological signs (depression, hallucinations/delusions, apathy) were first described in the late 19th century, whereas cognitive signs and dementia were delineated in the 20th century. However, elucidation of the underlying pathological processes from the lenticular nucleus to the substantia nigra, and from Lewy bodies to α-synuclein took a considerable amount of time during the 20th century. The discovery of degeneration of the dopaminergic nigrostriatal pathway and, subsequently, the advent of l-dopa therapy in the 1960s and 1970s revolutionized the treatment of PD and improved its differential diagnosis from atypical parkinsonian disorders. The implication of infectious and toxic environmental factors, suggested by the appearance of parkinsonian syndromes following an epidemic of encephalitis lethargica in the 1915–1925 era and the identification in 1983 of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), led to the incrimination of the role of pesticides. Since the 1990s, intensive research into the genetic forms of PD has paved the way towards the categorization of several genes and new pathogenic mechanisms. Major epidemiological, pathophysiological and therapeutic advances have also been made over the past 30 years, all made possible by the elaborations of international committees on rigorous diagnostic criteria based on clinical–pathological correlations and positive responses to l-dopa (UKPDBB, 1988; MDS clinical diagnostic criteria, 2015), and the use of specific quality-of-life, motor and cognitive scales (UPDRS, 1987; MDS-UPDRS, 2008).