Quality of life in Parkinson’s disease: Italian validation of the Parkinson’s Disease Questionnaire (PDQ-39-IT)

Translation and cross-cultural adaptation of the 39-item Parkinson’s Disease Questionnaire (PDQ-39) to the Italian culture was performed by Oxford University Innovation in 2008, but this version has never been validated. Therefore, we performed the process of validation of the Italian version of the PDQ-39 (PDQ-39-IT) following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The translated PDQ-39-IT was tested with 104 patients diagnosed with Parkinson’s disease (PD) who were recruited between June and October 2017. The mean age of the participants was 65.7 ± 10.2 years, and the mean duration of symptoms was 7.4 ± 5.3 years. The internal consistency of the PDQ-39-IT was assessed by Cronbach’s alpha and ranged from 0.69 to 0.92. In an assessment of test-retest reliability in 35 of the 104 patients, the infraclass correlation coefficient (ICC) ranged from 0.85 to 0.96 for the various subitems of the PDQ-39-IT (all p < 0.01). Spearman’s rank correlation coefficient for the validity of the PDQ-39-IT and the Italian version of the 36-Item Short Form (SF-36) was − 0.50 (p < 0.01). The results show that the PDQ-39-IT is a reliable and valid tool to assess the impact of PD on functioning and well-being. Thus, the PDQ-39-IT can be used in clinical and research practice to assess this construct and to evaluate the overall effect of different treatments in Italian PD patients

Effects of melatonin prolonged-release on both sleep and motor symptoms in Parkinson's disease: a preliminary evidence

background sleep-related symptoms, especially insomnia, are frequently reported by patients with parkinson's disease (PD) and can markedly affect motor symptoms and impair patients' quality of life. melatonin has been shown to improve sleep in PD patients. this pilot study aimed at evaluating the effects of a 3-month treatment with 2 mg melatonin prolonged-release (PR) on sleep and motor disability in PD patients. materials and methods twelve PD patients under stable antiparkinsonian treatment were enrolled in the study. before treatment (T0), motor dysfunction was assessed with unified parkinson's disease rating scale (UPDRS-III) and sleep architecture with polysomnography. subjective sleep quality was also assessed through pittsburgh sleep quality Index (PSQI) and daytime somnolence with epworth sleepiness Scale (ESS). patients then started melatonin PR and all measures were repeated at the end of treatment after 3 months (T1). results sleep latency significantly decreased from T0 to T1, but no other significant differences were found in PSG parameters. melatonin PR treatment significantly reduced the ESS scores from T0 to T1, while the PSQI scores presented a trend of improvement from T0 to T1. motor dysfunction was not improved by melatonin PR, although there was a trend in decreasing UPDRS-III. both clinical global improvement and patient clinical global impression documented an improvement in insomnia symptoms at T1. conclusions these findings suggest that melatonin may improve sleep symptoms in PD patients, although further evidence is needed in larger controlled studies to confirm these results and explore the possible direct and indirect influence of sleep improvement on motor dysfunction

Reduced GABA Content in the Motor Thalamus during Effective Deep Brain Stimulation of the Subthalamic Nucleus

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinson's disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (−30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy

Assessment of Psychometric Characteristics of Parkinson’s Disease Sleep Scale 2 and Analysis of a Cut-Off Score for Detecting Insomnia in Italian Patients with Parkinson’s Disease: A Validation Study

introduction: sleep disorders are frequent non-motor symptoms affecting patients with parkinson's disease (PD). Insomnia represents the most common sleep disorder. parkinson's disease Sleep Scale 2 (PDSS-2) is a specific tool to investigate sleep problems in PD. the general sleep disturbances scale (GSDS) was a general scale validated for the Italian population. our goal was to assess the psychometric characteristics of PDSS-2 and the GSDS in this population, calculating a cut-off score for insomnia symptoms by using subitems of PDSS-2. methods: patients admitted at the PD unit of the hospital of rome tor vergata outpatient clinic and those afferent to PD associations were asked to complete PDSS-2 and GSDS to be correlated to identify a cut-off for insomnia symptoms. Items 1,2,3,8,13 of PDSS-2 were used to detect insomnia. an ROC curve to assess a cut-off score for insomnia was determined. a cross-cultural analysis of PD population characteristics was performed. results: In total, 350 PD patients were recruited. cronbach's alpha was high for the total score (0.828 for PDSS-2 and 0.832 for GSDS). a cross-cultural analysis did not show any significant p-value. the ROC curve yielded an AUC of 0.79 (CI: 0.75-0.84). the cut-off value for insomnia disorder based on items 1,2,3,8,13 of PDSS-2 was &gt;10, demonstrating a sensitivity of 76% and a specificity of 69% in determining the presence of subjective insomnia symptoms in PD. discussion: PDSS-2 is demonstrated to be a valid, specific tool to address sleep disturbances in PD patients. a cut-off score of 10 for items 1,2,3,8,13 was identified for detecting insomnia symptoms in PD patients

Non-motor symptoms burden in motor-fluctuating patients with Parkinson's disease may be alleviated by safinamide: the VALE-SAFI study

parkinson's disease (PD) is characterized by motor symptoms often experienced in concomitance with non-motor symptoms (NMS), such as depression, apathy, pain, sleep disorders, and urinary dysfunction. the present study aimed to explore the effect of safinamide treatment on NMS and quality of life in motor-fluctuating PD patients. VALE-SAFI is an observational single-centre study performed in fluctuating PD patients starting safinamide treatment and followed for 6 months. the effects of safinamide on NMS, sleep, fatigue, depression and pain were assessed through validated sales. changes in the scales from baseline to the 6-month follow-up visit were analysed. 60 PD patients (66.67% males) were enrolled at baseline, and 45 patients completed the 6-month follow-up. PD patients improved motor symptoms at follow-up, with the significant reduction of motor fluctuations. the global score of the NMS Scale significantly decreased between baseline and the follow-up. regarding pain domains, patients reported a significant improvement in discolouration and oedema/swelling. further, a significant improvement was observed from baseline to follow-up in sleep quality measured through the pittsburgh sleep quality Index, while no changes were documented in daytime sleepiness. no differences were found in depression and fatigue between baseline and follow-up. finally, the patient's perception of the impact of PD on functioning and well-being decreased from baseline to follow-up. the present findings confirmed the beneficial effect of safinamide on both motor and non-motor symptoms, also improving the quality of life of PD patients. furthermore, these data support the positive effects of safinamide on pain and mood, as well as on sleep quality and continuity

Parkinson's disease motor progression in relation to the timing of REM sleep behavior disorder presentation: an exploratory retrospective study

REM sleep behavior disorder (RBD) is a frequent non-motor symptom of parkinson's disease (PD), and the timing of its presentation might have a role in the underlying neurodegenerative process. Here, we aimed to define the potential impact of probable RBD (pRBD) on PD motor progression. we conducted a longitudinal retrospective study on 66 PD patients followed up at the university hospital of rome tor vergata. patients were divided into three groups: with post-motor pRBD (pRBD(post), n = 25), without pRBD (pRBD(wo), n = 20), and with pre-motor pRBD (pRBD(pre), n = 21). Hoehn and Yahr (H&amp;Y) scores, unified PD rating scale (UPDRS) motor scores, and levodopa equivalent daily dose were collected at two follow-up visits conducted in a 5-year interval (T0 and T1). pRBD(post )patients had a greater rate of motor progression in terms of the H&amp;Y scale compared to pRBD(pre) and pRBD(wo) patients, without the influence of anti-parkinsonian treatment. these preliminary findings suggest that the post-motor occurrence of pRBD can be associated with an acceleration in PD motor progression

Association between hearing sensitivity and dopamine transporter availability in Parkinson's disease

In a previous study, we observed: significant hearing function impairment, assessed with pure tone audiometry and distortion product otoacoustic emissions, in patients with Parkinson's disease, compared with a matched control group, and lateralization of the hearing dysfunction, worse on the side affected by more pronounced Parkinson's disease motor symptoms. This study investigates the association between the basal ganglia dopamine transporter availability and the hearing function in Parkinson's disease patients, focusing also on the lateralization of both dysfunctions, with respect to that of the motor symptoms, and introducing a further distinction between patients with left-sided and right-sided predominant motor symptoms. Patients with right-handed Parkinson's disease with a recent estimation of 123I-FP-CIT striatal uptake were audiologically tested with pure tone audiometry and distortion product otoacoustic emissions. Thirty-nine patients were included in the study. A statistically significant association was found, in the left-side predominant group only, between the distortion product otoacoustic emission levels and the contralateral dopamine transporter availability, and between the hearing threshold and the dopamine transporter availability difference between the ipsi- and the contralateral sides. The hearing impairment lateralization correlated to the motor symptom asymmetry was found significant only in the left-side predominant patients. The association between hearing function and basal ganglia dopamine transporter availability supports the hypothesis that the peripheral hearing function decline associated with dopamine depletion is involved in Parkinson's disease development, with a significant difference between patients with left- and right-sided predominant motor symptoms. These findings also suggest that peripheral hearing function evaluation and its lateralization could be key elements for subtyping the disease

Dietary Vitamin E as a Protective Factor for Parkinson's Disease: Clinical and Experimental Evidence

Effective disease-modifying treatments are an urgent need for Parkinson's disease (PD). A putative successful strategy is to counteract oxidative stress, not only with synthetic compounds, but also with natural agents or dietary choices. Vitamin E, in particular, is a powerful antioxidant, commonly found in vegetables and other components of the diet. In this work, we performed a questionnaire based case-control study on 100 PD patients and 100 healthy controls. The analysis showed that a higher dietary intake of Vitamin E was inversely associated with PD occurrence independently from age and gender (OR = 1.022; 95% CI = 0.999–1.045; p &lt; 0.05), though unrelated to clinical severity. Then, in order to provide a mechanistic explanation for such observation, we tested the effects of Vitamin E and other alimentary antioxidants in vitro, by utilizing the homozygous PTEN-induced kinase 1 knockout (PINK1−/−) mouse model of PD. PINK1−/− mice exhibit peculiar alterations of synaptic plasticity at corticostriatal synapses, consisting in the loss of both long-term potentiation (LTP) and long-term depression (LTD), in the absence of overt neurodegeneration. Chronic administration of Vitamin E (alpha-tocopherol and the water-soluble analog trolox) fully restored corticostriatal synaptic plasticity in PINK1−/− mice, suggestive of a specific protective action. Vitamin E might indeed compensate PINK1 haploinsufficiency and mitochondrial impairment, reverting some central steps of the pathogenic process. Altogether, both clinical and experimental findings suggest that Vitamin E could be a potential, useful agent for PD patients. These data, although preliminary, may encourage future confirmatory trials

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns