Gender differences in microRNA expression in levodopa-naive PD patients.

Gender is an important factor influencing epidemiological and clinical features of Parkinson's disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs (miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman's correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62; p < 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44; p < 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.

Extensive validation study of the Parkinson's Disease Composite Scale.

BACKGROUND AND PURPOSE: A composite instrument able to rapidly and reliably assess the most relevant motor and non-motor afflictions suffered by Parkinson's disease (PD) patients in a real world clinic setting is an unmet need. The recently validated PD Composite Scale (PDCS) was designed to fulfil this gap as a quick, comprehensive PD assessment. The objective of this study was extensive evaluation of the PDCS's clinimetric properties using a large international sample. METHODS: This was a cross-sectional study in which the PDCS, the Movement Disorder Society Unified Parkinson's Disease Rating Scale and the Clinical Impression of Severity Index for PD were applied. Basic clinimetric attributes of the PDCS were analysed. RESULTS: In total, 776 PD patients were included. The PDCS total score showed negligible floor and ceiling effects. Three factors (54.5% of the variance) were identified: factor 1 included motor impairment, fluctuations and disability; factor 2, non-motor symptoms; and factor 3, tremor and complications of therapy. Cronbach's alpha was from 0.66 to 0.79. Inter-rater reliability showed weighted kappa values from 0.79 to 0.98 for items and intraclass correlation coefficient values from 0.95 (Disability) to 0.99 (Motor and total score). The Bland-Altmann method, however, showed irregular concordance. PDCS standard error of measurement and convergent validity with equivalent constructs of other measures were satisfactory (≥0.70). PDCS scores significantly differed by Hoehn and Yahr stage. CONCLUSION: Overall, in line with previous findings, the PDCS is a feasible, acceptable, valid, reliable and precise instrument for quickly and comprehensively assessing PD patients.

Early-morning OFF and levodopa dose failures in patients with Parkinson's disease attending a routine clinical appointment using Time-to-ON Questionnaire.

BACKGROUND AND PURPOSE: In patients with Parkinson's disease (PD) with motor fluctuations, total daily OFF time is comprised of both end-of-dose time and the time taken to turn ON with medication. However, little is known about the impact of delays in ON time. METHODS: This was a single-visit pilot study of fluctuating patients with PD attending a routine appointment. During a single visit, adult patients with idiopathic PD who were treated with levodopa for at least 1 year completed a questionnaire evaluating the time waiting for ON and the symptoms experienced while waiting to turn ON. Patients then completed a 5-day home time-to-ON diary, where they documented how long it took to turn ON following their first morning dose of levodopa in 5-min increments. RESULTS: A total of 151 consecutive patients completed the study survey, of whom 97 (64.2%) experienced motor fluctuations. Of the patients experiencing motor fluctuations, 54 (56%) reported delays in ON time (latency >30 min) following their first morning dose of levodopa. Half (51%) reported that they had experienced delayed ON at least once in the previous week and 21% reported having delayed ON during all seven mornings of the previous week. In addition, 10% of patients reported having dose failures on four or more mornings during the previous week. The most common symptoms experienced while waiting for ON were slowness (94.8%), fatigue (87.6%), reduced dexterity (82.5%), problems in walking (66.0%) and problems with balance (59.8%). CONCLUSION: Early-morning OFF problems such as delays in time to ON and dose failures are common in levodopa-treated patients with PD.

The Parkinson's Disease Composite Scale: results of the first validation study.

BACKGROUND AND PURPOSE: The aim was to validate the Parkinson's Disease Composite Scale (PDCS). METHODS: The study included 194 Parkinson's disease (PD) patients in five countries. Investigators completed the following scales: PDCS, the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale Version 2, Montreal Cognitive Assessment, the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease and the Clinical Impression of Severity Index for PD (CISI-PD). For test-retest analysis, a second administration of the PDCS was carried out in 61 stable patients (as per the CISI-PD) in 7-14 days after the first evaluation. The PDCS is a novel scale for PD with a total of 17 items divided into four domains: motor, non-motor, treatment complications and disability. RESULTS: Parkinson's Disease Composite Scale mean and median values were close. Skewness values were into the criterion limits (-1 to +1). The complete range of scores was covered for 14 of the 17 items (83.4%). A floor effect of 25.26% and 28.25% was observed in the complications and disability level dimensions due to the proportion of patients free of these difficulties. No relevant floor or ceiling effect was observed for the PDCS total score (1.03% and 0.52%, respectively). The stability of the scale appeared excellent with most items meeting weighted kappa and intraclass correlation coefficient values >0.80. The convergent validity of the PDCS with corresponding scores of the MDS-UPDRS showed high correlation values (rS  ≥ 0.60). The internal validity was into acceptable limits, with the majority of values higher than the minimal 0.30 threshold. The standard error of measurement suggested a satisfactory precision (SEM 3.81, <30% of the PDCS total score standard deviation). CONCLUSION: The PDCS appears to be a feasible, acceptable, reproducible and valid scale.

The Lee Silverman Voice Treatment (LSVT®) speech therapy in progressive supranuclear palsy.

BACKGROUND: The Lee Silverman Voice Treatment (LSVT®) was specifically created and tested to comply with the needs of individuals with Parkinson's disease (PD) and other neurological problems. This is a high effort intensive treatment that aims at increasing vocal intensity through the increase of subglottal air pressure, i.e. respiratory effort, for a better cordal adduction and vibration, following the motto "think loud". AIM: The main goal of this study is to inspect the efficacy of LSVT® treatment in progressive supranuclear palsy (PSP) patients. DESIGN: Longitudinal study. SETTING: Rehabilitative inpatient unit. POPULATION: Sixteen patients with PSP and 23 patients with idiopathic PD as control were enrolled in the study. METHODS: All patients underwent a training consisting in16 sessions of speech therapy following the LSVT® protocol. Initially the two groups of patients had similar voice problems, i.e. low volume and bad articulation of speech. RESULTS: A statistically significant improvement was found among the data collected before and after treatment in the PSP and Parkinson groups. Increase in maximum phonation duration and volume of voice in reading were similar in the two groups. Improvement in quality of voice and articulation were more significant in the PD group as compared to the PSP group. CONCLUSION: These results, along with previous findings, add further support to the generalized therapeutic impact of intensive voice treatment on respiratory and laryngeal functions in individuals with PSP. CLINICAL REHABILITATION IMPACT: The positive results, the absence of dropout and collateral effect following this clinical treatments with LSVT technique encouraged to use this technique in PSP patients.