Movement Disorders in Prionopathies: A Systematic Review.

Background: Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described.

Methods: We performed a systematic review of case reports and case series of pathologically- and genetically confirmed prionopathies. Timing of symptom and movement disorder onset were documented. Continuous variables were compared between two groups using the Wilcoxon rank sum test and between multiple groups using Kruskal-Wallis test. Categorical variables were compared using Fisher's exact test.

Results: A total of 324 cases were included in this analysis. Movement disorders were a common feature at the onset of symptoms in most prionopathies. Gait ataxia was present in more than half of cases in all types of prionopathies. The prevalence of limb ataxia (20%) and myoclonus (24%) was lower in Gerstmann-Sträussler-Scheinker disease compared to other prionopathies (p ≤ 0.004). Myoclonus was common but often a later feature in sporadic Creutzfeldt-Jakob disease (2 months before death). Chorea was uncommon but disproportionately prevalent in variant Creutzfeldt-Jakob disease (30% of cases; p < 0.001). In genetic Creutzfeldt-Jakob disease, E200K PRNP carriers exhibited gait and limb ataxia more often when compared to other mutation carriers.

Discussion: Movement disorders are differentially present in the course of the various prionopathies. The movement phenomenology and appearance are associated with the type of prion disease and the PRNP genotype and likely reflect the underlying pattern of neurodegeneration. Reliance on myoclonus as a diagnostic feature of sporadic Creutzfeldt-Jakob disease may delay its recognition given its relatively late appearance in the disease course.