Showing papers by "Francesco E. Pontieri published in 2019"

Early distinction of Parkinson-variant multiple system atrophy from Parkinson's disease.

Abstract: Distinguishing the Parkinson variant of MSA (MSA-P) from Parkinson’s disease (PD) is often difficult at disease onset. This is a major drawback for counseling of patients and timely enrollment into disease-modifying clinical trials. Clinicopathological studies consistently report that postural instability and autonomic failure emerge earlier in MSA-P than in PD, but it remains to be determined how this information can be integrated into the diagnostic work-up of patients with early parkinsonism. Here, we aimed at (1) quantifying the diagnostic yield of early-onset postural instability as well as cardiovascular and urological autonomic failure in differentiating MSA-P from PD and (2) merging early MSA-P distinctive features into a MSA-P diagnostic probability score. For this purpose, we retrospectively studied 161 PD and 29 MSA-P patients, who had undergone tilt-table testing at early disease, defined as Hoehn & Yahr (H&Y) stage <3 and/or disease duration <2 years. In the absence of neuropathological confirmation, established PD and MSA-P criteria were applied at last available visit by senior investigators and served as the clinical diagnostic gold standard. The diagnosis was further supported by cerebral MRI volumetry in all MSA-P patients with available MRI (n = 21) and in those PD patients with a followup time <24 months and disease duration <5 years (n = 19): patients with a mismatch between the final clinical and MRI diagnosis were excluded from further analysis (n = 4). Clinical features at early disease, associated with a diagnosis of MSA-P at last available visit, were investigated by means of χ, parametric, and nonparametric tests, followed by binary logistic regression analysis. An MSA-P diagnostic probability score was generated on the basis of early MSA-P discriminant variables. The study protocol was approved by the local ethical committee and performed according to the Declaration of Helsinki. Because of the retrospective design, no written informed consent was due. Processing of data followed the current Austrian regulation for data protection. An overview of the clinical-demographic characteristics of PD and MSA-P patients at early disease is provided in Supporting Information Table S1. By taking into account all significantly different clinicaldemographic traits at early disease, logistic regression analysis showed the following features to be associated with a final

Urinary retention discriminates multiple system atrophy from Parkinson's disease.

Abstract: physiological networks involved in involuntary movement. In general, tics may remit spontaneously in the natural course of GTS. Three-quarters of patients with GTS will have diminished tics by early adulthood. However, dramatic improvements are usually unlikely in refractory cases, even during adulthood. Thus, DBS may accelerate this natural course of remission. Indication for DBS must consider the possibility of natural remission in the future and that DBS must be continued in the long term once initiated. Our experiences suggest that DBS is a temporary but not necessarily lifelong treatment option for some patients with severe GTS. DBS may be terminated if improvement of the patient’s symptoms is sustained.

Alpha-synuclein in salivary gland as biomarker for Parkinson's disease.

Abstract: Estimates of the accuracy of clinical diagnosis of Parkinson's disease (PD) range between 46% and 90%, the accuracy of diagnosis dependent on prolonged clinical observation and clinical response to levodopa. For this reason, we need reliable diagnostic biomarkers. The cardinal hallmark of PD is alpha-synuclein aggregation in the brain. Demonstrating pathological alpha-synuclein in live patients would be useful for identifying and monitoring PD patients. By autopsy studies and in vivo studies, the presence of alpha-synuclein has been demonstrated even outside the central nervous system and the gastro-enteric tract appears to be the most promising candidate tissue for biopsy-taking and the esophagus and salivary glands appear to be the area with the highest concentration of alpha-synuclein. The purpose of our study is to conduct a review to determine the utility of salivary gland biopsy for the histological diagnosis of PD. A computerized medline study was carried out through the use of pubmed: using the MeSH terms: 'salivary gland biopsy for PD', 'PD and dysphagia', 'alpha-synuclein and salivary gland'. We found 9 articles about minor salivary glands and submandibular gland biopsy for diagnosis of PD. According to the results of this review, the submandibular gland biopsy is the test with the increased sensitivity and specificity compared to the biopsy of the minor salivary glands (sensitivity: 0.85 and 0.37 respectability and specificity: 0.96 and 0.94 respectively). New studies are necessary on a wider population to confirm these results.

Action Observation With Dual Task for Improving Cognitive Abilities in Parkinson's Disease: A Pilot Study

Abstract: Action observation therapy (AOT) has been recently proposed as a new rehabilitation approach for treatment of motor deficits in Parkinson's disease. To date, this approach has never been used to deal with cognitive deficits (e.g., deficits in working memory, attention), which are impairments that are increasingly recognized in Parkinsonian patients. Typically, patients affected by these dysfunctions have difficulty filtering out irrelevant information and tend to lose track of the task goal. In this paper, we propose that AOT may also be used to improve cognitive abilities of Parkinsonian patients if it is used within a dual task framework. We articulate our hypothesis by pivoting on recent findings and on preliminary results that were obtained through a pilot study that was designed to test the efficacy of a long-term rehabilitation program that, for the first time, uses AOT within a dual task framework for treating cognitive deficits in patients with Parkinson's disease. Ten Parkinson's disease patients underwent a 45-min treatment that consisted in watching a video of an actor performing a daily-life activity and then executing it while performing distractive tasks (AOT with dual task). The treatment was repeated three times per week for a total of 4 weeks. Patients' cognitive/motor features were evaluated through standard tests four times: 1 month before treatment, the first and the last day of treatment and 1 month after treatment. The results show that this approach may provide relevant improvements in cognitive aspects related to working memory (verbal and visuospatial memory) and attention. We discuss these results by pivoting on literature on action observation and recent literature demonstrating that the dual task method can be used to stimulate cognition and concentration. In particular, we propose that using AOT together with a dual task may train the brain systems supporting executive functions through two mechanisms: (i) stimulation of goal setting within the mirror neuron system through action observation and (ii) working memory and persistent goal maintenance through dual task stimuli.

Gender specific decrease of a set of circulating N-acylphosphatidyl ethanolamines (NAPEs) in the plasma of Parkinson’s disease patients

Abstract: Current markers of Parkinson’s disease (PD) fail to detect the early progression of disease state. Conversely, current omics techniques allow the investigation of hundreds of molecules potentially altered by disease conditions. Based on evidence previously collected by our group in a mouse model of PD, we speculated that a particular set of circulating lipids might be significantly altered by the pathology. The aim of current study was to evaluate the potential of a particular set of N-acyl-phosphatidylethanolamines (NAPEs) as potential non-invasive plasma markers of ongoing neurodegeneration from Parkinson’s disease in human subjects. A panel of seven NAPEs were quantified by LC–MS/MS in the plasma of 587 individuals (healthy controls, n = 319; Parkinson’s disease, n = 268); Random Forest classification and statistical modeling was applied to compare Parkinson’s disease versus controls. All p-values obtained in different tests were corrected for multiplicity by controlling the false discovery rate (FDR). The results indicate that this panel of NAPEs is able to distinguish female PD patients from the corresponding healthy controls. Further to this, the observed downregulation of these NAPEs is in line with the results in plasma of a mouse model of Parkinson’s (6-OHDA). In the current study we have shown the downregulation of NAPEs in plasma of PD patients and we thus speculate that these lipids might serve as candidate biomarkers for PD. We also suggest a molecular mechanism, explaining our findings, which involves gut microbiota.

Alexithymia and anhedonia in early Richardson's syndrome and progressive supranuclear palsy with predominant parkinsonism

Abstract: INTRODUCTION Phenotypic variants of progressive supranuclear palsy (PSP) are all characterized by the combination of motor symptoms of parkinsonism with a number of neuropsychiatric and cognitive disorders. Despite the strong effort in characterizing these features in PSP, alexithymia and anhedonia have not been investigated at present. Here, we aimed at investigating the qualitative and quantitative differences of alexithymia and anhedonia in the two more frequent variants of PSP, Richardson's syndrome (PSP-RS) and PSP with predominant parkinsonism (PSP-P) compared to Parkinson's disease (PD) patients recruited within 24 months after the onset of motor symptoms. METHODS One hundred fifty-five PD, 11 PSP-P, and 14 PSP-RS patients underwent clinical, neuropsychiatric, and neuropsychological evaluations. Alexithymia was assessed using the Toronto Alexithymia Scale-20 item (TAS-20), and hedonic tone was measured by the Snaith-Hamilton Pleasure Scale (SHAPS). RESULTS In PSP-P and PSP-RS patients, the frequency of alexithymia diagnosis was higher than in PD. On the TAS-20 scores, PSP-RS performed worse in the total score and in F2 sub-scale when compared to PD. Among patients with diagnosis of depression, PSP-RS showed higher scores in TAS-20 total and TAS-20 F2 than PD. No significant differences in TAS-20 scores were found in nondepressed patients. Finally, we did not find significant differences among PD, PSP-P, and PSP-RS groups in the SHAPS scores. CONCLUSIONS Alexithymia is identifiable very early in PSP-P and PSP-RS patients. Alexithymic symptoms differentiate PSP-RS group from PD group but not between the two subtypes of PSP. Further, alexithymia in PSP seems to be predicted by the presence of depression. Altered emotional capability could be related to specific neurophysiological dysfunction occurring precociously in PSP; therefore, its identification could orient the diagnosis toward PSP cases.