LAUSR

Two hundred years ago, James Parkinson, a London apothecary and surgeon, published his observations on several patients who had developed involuntary shaking, weakness, and altered posture and gait, which he called “the shaking palsy” or paralysis agitans. Careful perusal of this landmark essay also reveals the astute observations Parkinson made on the behavioral, sleep, and autonomic components of Parkinson’s disease (PD), now defined as nonmotor aspects of PD. Today is regarded as a multisystem-, multiorgan-, multi-neurotransmitter-driven complex disorder with a long prodromal period, a concept considerably different even from what we believed 2 decades ago. An unique meeting supported by the Movement Disorders Society in March 2017, held at the renowned Royal Society in London, celebrated the life and times of James Parkinson, who lived and worked from 1 Hoxton Square, a few miles from the venue (see Supplementary Material). All aspects of the modern concept of PD were examined in a series of 20 lectures spanning “bench to bedside” by key opinion leaders with more then 300 international delegates packing the venue. It was appropriate to begin by looking at the life and times of James Parkinson, and Brian Hurwitz pointed out his many achievements in the fields of medicine and geology as well as the active role Parkinson played in politics. Parkinson’s observational skills were superb, and he correctly described a prodromal phase of the condition. In a 40-year-old woman he referred to as “A.B.,” he writes that she had “great pain in both the arms, extending from the shoulders to the finger ends” and also suffered from “a rheumatic affection of the deltoid muscle” involving pain down the arm. Parkinson then concluded that it was “not improbable that attacks of this kind...might lay the foundation of this lamentable disease.” This is most likely the first description of the earliest nonmotor symptom of PD. The heterogeneity of the cause of PD was explored in a discussion on the role of genetics and environment by Vincenzo Bonifati. He pointed out that the complex disorder of PD can be caused by mutations in multiple genes, but there is a variable role environment and stochastic influences that culminate in the clinical expression of PD interacting with genetic susceptibility. Although a-synuclein is ubiquitous in Lewy bodies, mutations in the a-synuclein gene remain a rare monogenic cause of PD in contrast to the glucocerebrocidase gene (GBA) and the leucinerich repeat kinase 2 genes. Low-penetrant mutations of these genes represent a more common risk for PD. The ethnic variation in leucine-rich repeat kinase 2 gene mutations and the high prevalence in some populations (eg, Ashkenazy Jewish, Arab-Berber) have helped in linking the pathogenesis of familial and sporadic PD. Other discussions focused on a prion-like process that has been proposed as a possible pathological process that may be linked to the pathogenesis of PD and is based on cell-to cell spreading of a misfolded protein as suggested in a recent paper from Mao and colleagues. The role of GBA mutation in particular was also explored in another talk by A.H.V. Schapira, who spoke about the possible modulation GCase activity using gene therapy and also chaperone active molecules such as ambroxol and -----------------------------------------------------------*Corresponding author: Professor K. Ray Chaudhuri, Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, King’s College London, Cutcombe Road, London, SE5 9RT; [email protected]