The Emerging Role of Phosphodiesterases in Movement Disorders

Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of the cyclic nucleotides cyclic adenosine monophosphate and cyclic guanosine monophosphate, which act as intracellular second messengers for many signal transduction pathways in the central nervous system. Several classes of PDE enzymes with specific tissue distributions and cyclic nucleotide selectivity are highly expressed in brain regions involved in cognitive and motor functions, which are known to be implicated in neurodegenerative diseases, such as Parkinson's disease and Huntington's disease. The indication that PDEs are intimately involved in the pathophysiology of different movement disorders further stems from recent discoveries that mutations in genes encoding different PDEs, including PDE2A, PDE8B, and PDE10A, are responsible for rare forms of monogenic parkinsonism and chorea. We here aim to provide a translational overview of the preclinical and clinical data on PDEs, the role of which is emerging in the field of movement disorders, offering a novel venue for a better understanding of their pathophysiology. Modulating cyclic nucleotide signaling, by either acting on their synthesis or on their degradation, represents a promising area for development of novel therapeutic approaches. The study of PDE mutations linked to monogenic movement disorders offers the opportunity of better understanding the role of PDEs in disease pathogenesis, a necessary step to successfully benefit the treatment of both hyperkinetic and hypokinetic movement disorders. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Unravelling of the paroxysmal dyskinesias

Paroxysmal dyskinesias (PxD) refer to a rare group of clinically and genetically heterogeneous disorders presenting with recurrent attacks of abnormal movements, typically dystonia, chorea or a combination thereof, without loss of consciousness. Classically, PxD have been categorised according to their triggers and duration of the attacks, but increasing evidence suggests that there is a certain degree of clinical and genetic overlap and challenges the concept that one phenotype is attributable to one single aetiology. Here we review the increasing spectrum of genetic conditions, as well as of other non-genetic disorders, that might present with PxD, provide criteria for case definition and propose a diagnostic workup to reach a definitive diagnosis, on which treatment is heavily dependent

Shoulder-touch test to reveal incongruencies in persons with functional motor disorders

Clinical experience suggests that many patients with functional motor disorders (FMD), despite reporting severe balance problems, typically do not fall frequently. This discrepancy may hint towards a functional component. Here, we explored the role of the Shoulder-Touch test, which features a light touch on the patient's shoulders to reveal a possible functional etiology of postural instability

Facial Emotion Recognition and Expression in Parkinson's Disease: An Emotional Mirror Mechanism?

BACKGROUND AND AIM: Parkinson's disease (PD) patients have impairment of facial expressivity (hypomimia) and difficulties in interpreting the emotional facial expressions produced by others, especially for aversive emotions. We aimed to evaluate the ability to produce facial emotional expressions and to recognize facial emotional expressions produced by others in a group of PD patients and a group of healthy participants in order to explore the relationship between these two abilities and any differences between the two groups of participants. METHODS: Twenty non-demented, non-depressed PD patients and twenty healthy participants (HC) matched for demographic characteristics were studied. The ability of recognizing emotional facial expressions was assessed with the Ekman 60-faces test (Emotion recognition task). Participants were video-recorded while posing facial expressions of 6 primary emotions (happiness, sadness, surprise, disgust, fear and anger). The most expressive pictures for each emotion were derived from the videos. Ten healthy raters were asked to look at the pictures displayed on a computer-screen in pseudo-random fashion and to identify the emotional label in a six-forced-choice response format (Emotion expressivity task). Reaction time (RT) and accuracy of responses were recorded. At the end of each trial the participant was asked to rate his/her confidence in his/her perceived accuracy of response. RESULTS: For emotion recognition, PD reported lower score than HC for Ekman total score (p<0.001), and for single emotions sub-scores happiness, fear, anger, sadness (p<0.01) and surprise (p = 0.02). In the facial emotion expressivity task, PD and HC significantly differed in the total score (p = 0.05) and in the sub-scores for happiness, sadness, anger (all p<0.001). RT and the level of confidence showed significant differences between PD and HC for the same emotions. There was a significant positive correlation between the emotion facial recognition and expressivity in both groups; the correlation was even stronger when ranking emotions from the best recognized to the worst (R = 0.75, p = 0.004). CONCLUSIONS: PD patients showed difficulties in recognizing emotional facial expressions produced by others and in posing facial emotional expressions compared to healthy subjects. The linear correlation between recognition and expression in both experimental groups suggests that the two mechanisms share a common system, which could be deteriorated in patients with PD. These results open new clinical and rehabilitation perspectives