Current understanding and management of Parkinson disease

Abstract

PubMed query for “Parkinson disease” yields more than 2,000 articles per year for each of the last 5 years. That is a daunting pile of bedside reading for even the most diligent neurologist. This review highlights 5 emerging topics that are changing our current understanding and management of Parkinson disease (PD). When using the term PD, we mean Lewy body parkinsonism as defined by the clinical criteria of the United Kingdom Parkinson's Disease Society Brain Bank. Other parkinsonian syndromes, such as progressive supranuclear palsy and multiple system atrophy, are beyond the scope of this review. Clinicians are frequently faced with the question, posed by a newly diagnosed patient or family member: “Is Parkinson's genetic?” This apparently simple question has a complex answer. In a small minority of cases, there are defined genes that, when mutated, cause PD. For example, mutations in α-synuclein ( SNCA ), leucine-rich repeat kinase-2 ( LRRK2 ), Parkin , PTEN-induced kinase-1 ( PINK1 ), and DJ-1 have been convincingly demonstrated to cause familial PD but often without a typically Mendelian pattern of inheritance. Families with clear autosomal recessive and dominant patterns are rare. Yet the relative risk of developing PD is more than 3 times higher for an asymptomatic individual when a first-degree relative is affected with sporadic PD.1 Even where there is clear familial clustering of cases, a causative gene may not be identified. What is the source of this “missing heritability”? Some insight has come from recent genome-wide association studies2,3 of large numbers of patients. These analyses—essentially case-control studies where “exposures” are defined by genotyping individuals over a large number of sites of variation in the genome—have identified a number of novel “risk genes” that contribute to the overall chance of developing PD. Importantly, some of these were loci already implicated in familial PD ( SNCA, LRRK2 …