Background. In order to develop multifaceted fall prevention strategies for people with Parkinson’s disease (PD), greater understanding of the impact of physical and cognitive performance on falls is ...required. Objective. We aimed to identify the relative contribution of a comprehensive range of physical and cognitive risk factors to prospectively-measured falls in a large sample of people with PD and develop an explanatory multivariate fall risk model in this group. Methods. Measures of PD signs and symptoms, freezing of gait, balance, mobility, proprioception, leg muscle strength, and cognition were collected on 205 community-dwelling people with PD. Falls were monitored prospectively for 6 months using falls diaries. Results. A total of 120 participants (59%) fell during follow-up. Freezing of gait (P < .001), dyskinesia (P = .02), impaired anticipatory and reactive balance (P < .001), impaired cognition (P = .002), reduced leg muscle strength (P = .006), and reduced proprioception (P = .04) were significantly associated with future falls in univariate analyses. Freezing of gait (risk ratio RR = 1.03, 95% confidence interval CI = 1.00-1.05, P = .02), impaired anticipatory (RR = 1.01, 95% CI = 1.00-1.02, P = .03) and reactive (RR = 1.26, 95% CI = 1.01-1.58, P = .04) balance, and impaired orientation (RR = 1.28, 95% CI = 1.01-1.62, P = .04) maintained significant associations with falls in multivariate analysis. Conclusion. The study findings elucidate important physical and cognitive determinants of falls in people with PD and may assist in developing efficacious fall prevention strategies for this high-risk group.
Genetic early-onset parkinsonism presenting from infancy to adolescence (≤21 years old) is a clinically diverse syndrome often combined with other hyperkinetic movement disorders, neurological and ...imaging abnormalities. The syndrome is genetically heterogeneous, with many causative genes already known. With the increased use of next-generation sequencing in clinical practice, there have been novel and unexpected insights into phenotype-genotype correlations and the discovery of new disease-causing genes. It is now recognized that mutations in a single gene can give rise to a broad phenotypic spectrum and that, conversely different genetic disorders can manifest with a similar phenotype. Accurate phenotypic characterization remains an essential step in interpreting genetic findings in undiagnosed patients. However, in the past decade, there has been a marked expansion in knowledge about the number of both disease-causing genes and phenotypic spectrum of early-onset cases. Detailed knowledge of genetic disorders and their clinical expression is required for rational planning of genetic and molecular testing, as well as correct interpretation of next-generation sequencing results. In this review we examine the relevant literature of genetic parkinsonism with ≤21 years onset, extracting data on associated movement disorders as well as other neurological and imaging features, to delineate syndromic patterns associated with early-onset parkinsonism. Excluding PRKN (parkin) mutations, >90% of the presenting phenotypes have a complex or atypical presentation, with dystonia, abnormal cognition, pyramidal signs, neuropsychiatric disorders, abnormal imaging and abnormal eye movements being the most common features. Furthermore, several imaging features and extraneurological manifestations are relatively specific for certain disorders and are important diagnostic clues. From the currently available literature, the most commonly implicated causes of early-onset parkinsonism have been elucidated but diagnosis is still challenging in many cases. Mutations in ∼70 different genes have been associated with early-onset parkinsonism or may feature parkinsonism as part of their phenotypic spectrum. Most of the cases are caused by recessively inherited mutations, followed by dominant and X-linked mutations, and rarely by mitochondrially inherited mutations. In infantile-onset parkinsonism, the phenotype of hypokinetic-rigid syndrome is most commonly caused by disorders of monoamine synthesis. In childhood and juvenile-onset cases, common genotypes include PRKN, HTT, ATP13A2, ATP1A3, FBX07, PINK1 and PLA2G6 mutations. Moreover, Wilson's disease and mutations in the manganese transporter are potentially treatable conditions and should always be considered in the differential diagnosis in any patient with early-onset parkinsonism.
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