Bone mineral density assessment in patients with cystinuria.

BACKGROUND: Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainly include nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria. METHODS: Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores. RESULTS: Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99 mL/min/1.73 m2. Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤ - 2 at any site, was 15%. Average Z-scores were negative across most sites. CONCLUSIONS: Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when their kidney function is normal.

Renal Cystinuria and Immune Cells (T Lymphocytes) Dysfunction: What We Know about?

INTRODUCTION: Cystinuria (CYS) is the most common monogenic kidney stone disease. METHODS: Starting from an unusual case of CYS associated to primary sclerosing cholangitis, inflammatory bowel disease (IBD), and autoimmune hepatitis in a young male, we carefully review the literature and propose here a working hypothesis regarding the potential risk of cystinuric patients to develop conditions due to immune system dysregulation. To corroborate this hypothesis, we retrospectively evaluate the frequency of dysimmunity in a monocentric cohort including 36 cystinuric patients compared to healthy and disease controls. RESULTS: CYS patients have an increased prevalence of atopic disease compared to disease controls (p = 0.03) and 16.7% of CYS subjects were diagnosed with allergic disease to a variety of antigens. CONCLUSION: Further studies are needed to define the relationship between proximal tubular transport defect of CYS and dysregulated immunity.

miRNA profile is altered in a modified EAE mouse model of multiple sclerosis featuring cortical lesions.

Cortical lesions represent a hallmark of multiple sclerosis and are proposed as a predictor of disease severity. microRNAs are suggested to be important players in the disease pathogenesis and the experimental autoimmune encephalomyelitis animal model. We implemented a mouse model recapitulating more closely the human pathology as it is characterized by both an autoimmune heterogeneity and the presence of cortical lesions, two parameters missing in experimental autoimmune encephalomyelitis. In our model, mice clustered in two groups displaying high or low clinical scores. Upon cortical cytokine injection, lesions appeared with a specific topography while cortical miRNA profiles were altered. These two features differed according to disease severity. We evidenced changes in miRNA regulators and targets suggesting that miRNA alteration had functional repercussions that could explain the differences in cortical lesions. This model represents a crucial tool for the study of both miRNA involvement and cortical lesion formation in disease pathogenesis.

The HLA-DRB1 risk alleles for multiple sclerosis are differentially expressed in blood cells of patients from Southern Italy.

HLA gene expression has an important role in the autoimmune disease predisposition. We investigated the mRNA expression profile of the risk alleles HLA-DRB1*15 and HLA-DRB1*13 in a cohort of subjects both multiple sclerosis (MS) patients and healthy controls. Moreover, we explored the expression of the allele HLA-DRB1*11 that is very frequent in our cohort from southern Italy. We found that the expression of MS-associated alleles in heterozygous MS patients was always higher than the nonassociated alleles. The differential risk allele expression occurred also in nonaffected subjects, though with a lower increment compared to MS patients.

Pragmatic abilities in multiple sclerosis: The contribution of the temporo-parietal junction.

Recent studies showed that multiple sclerosis (MS) patients might experience communicative deficits, specifically in pragmatics (i.e., the ability to integrate the context-dependent aspects of language). A crucial region for pragmatics is the temporo-parietal junction, in particular the so-called Geschwind's area (GA), which is involved in high-level language processes, including the comprehension of narratives, metaphor, and irony. We evaluated the relationship between pragmatic abilities, measured through the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) test, and the functional connectivity (FC) of the bilateral GAs, assessed through a seed-based analysis of Resting-State fMRI in patients with MS. A positive correlation was observed between APACS scores and the FC for both the right and the left GA and the paracingulate cortex. Our findings suggest that the brain FC for social communication involves connections extending over both hemispheres, including right and left GAs and right and left paracingulate cortex, possibly impaired in patients with MS. This study offers preliminary evidence for future researches enrolling also a control sample to explore the involvement of GA in pragmatics in neurological disorders as well as in healthy conditions.

Aerodynamic findings and Voice Handicap Index in Parkinson's disease.

OBJECTIVE: To verify possible relations between vocal disability and aerodynamic measures in selected Parkinson's disease (PD) patients with low/moderate-grade dysphonia. METHODS: Fifteen idiopathic dysphonic PD male patients were examined and compared with 15 euphonic subjects. Testing included the following measures: Voice Handicap Index (VHI), maximum phonation time (MPT), mean estimated subglottal pressure (MESGP), mean sound pressure level (MSPL), mean phonatory power (MPP), mean phonatory efficiency (MPE) and mean phonatory resistance (MPR). RESULTS: Statistical analysis showed: a significant reduction in MPR and MSPL in PD subjects compared to the healthy ones; a significant positive correlation between VHI score and MSPL, MPR, MPP, MESGP and a significant negative correlation between VHI and MTP within PD subjects. Test for multiple linear regression showed a significant correlation between VHI score, MPT, MPR and MSPL. CONCLUSIONS: A relationship between VHI and aerodynamic measures was shown in the present study. Compensatory mechanisms may aggravate vocal disability in PD subjects.

Communication in Multiple Sclerosis: Pragmatic Deficit and its Relation with Cognition and Social Cognition.

OBJECTIVE: Cognitive functions have been largely investigated in multiple sclerosis. Less attention has been paid to social communication abilities, despite their presumptive affect on quality of life. We run the first comprehensive assessment of pragmatic skills in multiple sclerosis, evaluating also the relationship between pragmatics and other cognitive domains. METHODS: Forty-two multiple sclerosis patients and 42 controls were tested for pragmatic abilities, neuro-cognition, social cognition, depression, and fatigue. RESULTS: Patients performed poorly in most pragmatic tasks compared to controls. Globally, 55% of patients performed below the 5th percentile in the total pragmatic score. Notably, pragmatic skills did not differ between cognitively impaired and unimpaired patients. However, an association was found between pragmatics and verbal fluency, as measured in the Word List Generation. Finally, we observed an association of pragmatic abilities with social cognition, and a trend with psychosocial functioning. CONCLUSION: Overall, the study shows a diffuse pragmatic impairment in multiple sclerosis, not associated with the patient's global neuropsychological profile. By contrast, our findings suggest a close relation between pragmatics and specific cognitive aspects such as executive functions, and between pragmatics and social cognition. This study underlines the need of looking beyond classical cognitive performance, to consider underestimated communicative disturbances of high clinical relevance.

Immunometabolic profiling of T cells from patients with relapsing-remitting multiple sclerosis reveals an impairment in glycolysis and mitochondrial respiration.

BACKGROUND: Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression. METHODS AND RESULTS: In this report, we observed that extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), indicators of glycolysis and oxidative phosphorylation, respectively, were impaired during T cell activation in naïve-to-treatment relapsing remitting (RR)MS patients when compared with healthy controls. These results were also corroborated at biochemical level by a reduced expression of the glycolitic enzymes aldolase, enolase 1, hexokinase I, and by reduction of Krebs cycle enzymes dihydrolipoamide-S-acetyl transferase (DLAT) and dihydrolipoamide-S-succinyl transferase (DLST). Treatment of RRMS patients with interferon beta-1a (IFN beta-1a) was able to restore T cell glycolysis and mitochondrial respiration as well as the amount of the metabolic enzymes to a level comparable to that of healthy controls. These changes associated with an up-regulation of the glucose transporter-1 (GLUT-1), a key element in intracellular transport of glucose. CONCLUSIONS: Our data suggest that T cells from RRMS patients display a reduced engagement of glycolysis and mitochondrial respiration, reversible upon IFN beta-1a treatment, thus suggesting an involvement of an altered metabolism in the pathogenesis of MS.

The effects of mechanical focal vibration on walking impairment in multiple sclerosis patients: A randomized, double-blinded vs placebo study.

BACKGROUND: Multiple Sclerosis is a heterogeneous disorders involving in early stage gait and balance. Together with immunomodulating therapies, rehabilitation had a crucial role in improving motor tasks and quality of life. Between the emerging techniques, Focal Vibrations (FV) could play a role, but they have been used in MS only to reduce muscle tone and fatigue alone or together with botulinum toxin. OBJECTIVE: To assess whether FV is effective on walking impairment in a cohort of MS patients. METHODS: We performed a single-centre randomized, double-blind, sham-controlled study to investigate efficacy of FV vs sham vibration in 20 RR MS patients. Ten patients received treatment with the active device and ten patients sham treatment. Demographical, clinical and gait instrumental data analysis have been collected for each patient at baseline (T0), after treatment (T1) and after three weeks of wash out (T2). RESULTS: Both groups were clinically and demographically comparable. Treated patients showed significant improvements during the first right step (FRS) (p = 0.007), average stride lenght (ASL) (p = 0.012), double support right (DSRT) (p = 0.016) and left (DSLT) (p = 0.003) time. Non-treated patients didn't show any significance for any dynamic variables. Moreover, on posturographic measurements we registered only a trend towards significance in swing area with eyes open (SAEO) (p = 0.087). We also found in treated group significant improvements in FRT (p = 0.018); BBS (p = 0.037) and FSS scales (p = 0.038) between T1 and T0. Lastly, we found a significant inverse correlation in the treated group between disease duration and percentage of improvement for DSLT (r = - 0.775; p = 0.014) in T1 vs T0 and percentage of improvement of FSS, with an inverse correlation with both disease duration (r = - 0.775; p = 0.014) and AGE (r = - 0.733, p = 0.025) in T1 vs T0CONCLUSION: Our results suggest a beneficial effect of FV on walking impairment in MS patients suffering from spasticity and/or postural instability, which partially lasted until follow up.

Microalbuminuria predicts the recurrence of cardiovascular events in patients with essential hypertension.

OBJECTIVES: Microalbuminuria (MAU) is associated with an enhanced risk of cardiovascular events. The prevalence of MAU and its prognostic impact has an important role in the stratification of cardiovascular risk in patients with essential hypertension. This is an observational, prospective study performed by 13 general practitioners aiming at assessing the prevalence and prognostic relevance of MAU in essential hypertension. METHODS: Patients with essential hypertension and with recent determination of MAU were enrolled into the study by general practitioners, and were followed up for 3 years. Primary end point was the occurrence of major cardiovascular events during the follow-up. RESULTS: Out of 1024 unselected patients, consecutively enrolled from January 2009 to March 2010, 804 completed the 3-year follow-up. Patients were categorized into two groups according to the absence (n = 523, 65%) or presence (n = 281, 35%) of MAU. During the follow-up, 41 cardiovascular events (1.69 events/100 patient-years) were reported. The presence of MAU was not associated with increased risk of cardiovascular events (adjusted hazard ratio = 1.32; 95% confidence interval 0.290-4.340, P = 0.097). When the analysis was restricted to the patients with previous cardiovascular event, MAU (adjusted hazard ratio = 2.18; 95% confidence interval 0.42-2.43, P = 0.031), together with age, metabolic syndrome, diabetes, and smoking, independently predicted the occurrence of cardiovascular events. CONCLUSION: Presence of MAU in patients with essential hypertension is not associated with increased risks of cardiovascular events. At the variance, in patients with previous cardiovascular events, MAU was found to predict recurrent events. Thus, the assessment of MAU could be considered a useful tool in secondary prevention.

Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-ß1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis.

Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Although subcutaneous administration of interferon (IFN)-ß1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebo-controlled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-ß1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-ß1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-γ, tumor necrosis factor-α, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-ß1a-related adverse effects in RR-MS.

Serum uric acid is associated with apathy in early, drug-naïve Parkinson's disease.

Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson's disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.

The management of multiple sclerosis by reference centers in south of Italy: a 2011 survey on health demands and needs in Campania region.

This cross-sectional study has investigated the diagnostic and therapeutic management of patients suffering from multiple sclerosis (MS) in the Campania Region (Italy). A survey involving all the reference centers for MS in Campania Region was conducted from March to August 2011. Centers responded to a web-administered questionnaire on management and clinical characteristics of MS patients. In the study period, 3263 patients (mean age 37 years, 66 % females) accessed the centers. Patients received a first diagnosis of MS in 161 cases (4.9 %). About 37 % of the subjects without a previous diagnosis came to the centers on their own initiative. All patients underwent a complete neurological examination and expanded disability status scale. The other most common investigations were magnetic resonance imaging (44.0 %) and evoked potentials (22.1 %). The number of treated patients was 2797 (87.1 %). The most used drugs were interferon ß and glatiramer acetate. The time between diagnosis and initiation of therapy exceeded 6 months in 32 % of cases. Second-line drugs were under-used: 16 % of patients who might benefit from them show high clinical and radiological disease activity despite treatment with immunomodulant drugs. The MS care management of the surveyed centers showed consistent margins for improvement in 2011. Even though these data do not represent the current situation, they can be used to monitor improvements in MS care.

No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon ß1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).

BACKGROUND: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. OBJECTIVES: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. METHODS: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon ß1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. RESULTS: A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. CONCLUSIONS: Our results suggest that the combination of atorvastatin and interferon ß1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis.

The IFN-ß 1b effect on Cu Zn superoxide dismutase (SOD1) in peripheral mononuclear blood cells of relapsing-remitting multiple sclerosis patients and in neuroblastoma SK-N-BE cells.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease leading to axonal injury. Even if the etiology of MS is still unknown the disease begins with inflammation involving autoreactive T lymphocytes activation in genetically susceptible subjects. Interferon beta-1b (IFN ß 1b) is one of the most used drug in the MS therapy. The results obtained in this study show that the concentration of SOD1 in CSF of relapsing-remitting MS (RR-MS) patients, evaluated by enzyme-linked immunosorbent assay (ELISA), is decreased compared to pathological controls. Moreover, the Western blotting analysis demonstrated that SOD1 in human peripheral blood mononuclear cells (PBMC) in healthy controls was significantly higher compared to MS subjects before starting DMT therapy. In addition IFN ß 1b therapy causes an increase of intracellular SOD1 protein as well as mRNA levels in PBMC. Moreover, the treatment of neuroblastoma SK-N-BE cells with IFN ß 1b increased SOD1 protein and mRNA levels; these data also suggest that neuroprotective effect of this physiological molecule is, at least in part, carried out through its effect on SOD1. This study demonstrate that DMT therapy is able to increase SOD1 expression in PBMC of RR-MS patients. Therefore, the effectiveness of DMT therapy can be ascribed, at least in part, to an increased levels of this antioxidant enzyme as further confirmed by in vitro studies in SK-N-BE cells.

Prognostic value of combined target-organ damage in patients with essential hypertension.

BACKGROUND: Whether the combination of chronic kidney disease (CKD) and left ventricular hypertrophy (LVH) affects the cardiovascular (CV) risk in patients with uncomplicated hypertension is poorly investigated. The aim of this study was to assess the effects of LVH, CKD, and their combination on CV events in hypertension. METHODS: This study analyzed 1,078 patients with essential hypertension. RESULTS: LVH was present in 104 (9.6%) patients, CKD was present in 556 (51.5%) patients, and the combination of LVH and CKD was found in 174 (16.1%) patients. During the follow-up (median = 84 months), 52 CV events were observed (0.64 events/100 patient-years): 6 (2.4%) in patients without target-organ damage (TOD), 6 (5.7%) in patients with LVH, 20 (3.6%) in patients with CKD, and 20 (11.4%) in patients with combined LVH+CKD. Adjusted hazard ratio (HR) for CV events was 1.62 (P = 0.34) for LVH, 0.951 (P = 0.94) for CKD, and 2.45 (P = 0.03) for LVH+CKD. After multivariable Cox proportional hazard analysis, the combination of LVH+CKD was significantly associated with risk of CV events, when the model was adjusted for sex and age (HR = 2.447; P = 0.03) and for the presence of 1 CV risk factor (HR = 3.226; P = 0.02). In contrast, the association of LVH+CKD was no longer significant when the model was adjusted for sex, age, and the presence of ≥ 2 CV risk factors. CONCLUSIONS: The results of this study highlight the relevance of the interactions between TODs and hemodynamic, anthropometric, and metabolic abnormalities in the CV risk stratification of patients with essential hypertension.

Small non-coding RNA signature in multiple sclerosis patients after treatment with interferon-ß.

BACKGROUND: Non-coding small RNA molecules play pivotal roles in cellular and developmental processes by regulating gene expression at the post-transcriptional level. In human diseases, the roles of the non-coding small RNAs in specific degradation or translational suppression of the targeted mRNAs suggest a potential therapeutic approach of post-transcriptional gene silencing that targets the underlying disease etiology. The involvement of non-coding small RNAs in the pathogenesis of neurodegenerative diseases such as Alzheimer's , Parkinson's disease and Multiple Sclerosis has been demonstrated. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by chronic inflammation, demyelination and scarring as well as a broad spectrum of signs and symptoms. The current standard treatment for SM is interferon ß (IFNß) that is less than ideal due to side effects. In this study we administered the standard IFN-ß treatment to Relapsing-Remitting MS patients, all responder to the therapy; then examined their sncRNA expression profiles in order to identify the ncRNAs that were associated with MS patients' response to IFNß. METHODS: 40 IFNß treated Relapsing-Remitting MS patients were enrolled. We analyzed the composition of the entire small transcriptome by a small RNA cloning method, using peripheral blood from Relapsing-Remitting MS patients at baseline and 3 and 6 months after the start of IFNß therapy. Real-time qPCR from the same patients group and from 20 additional patients was performed to profile miRNAs expression. RESULTS: Beside the altered expression of several miRNAs, our analyses revealed the differential expression of small nucleolar RNAs and misc-RNAs.For the first time, we found that the expression level of miR-26a-5p changed related to INF-ß response. MiR-26a-5p expression was significantly higher in IFN-ß treated RRMS patients at 3 months treatment, keeping quite stable at 6 months treatments. CONCLUSIONS: Our results might provide insights into the mechanisms of action of IFN-ß treatment in MS and provide fundamentals for the development of new biomarkers and/or therapeutic tools.

Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients.

BACKGROUND: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking. METHODS: In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment. RESULTS: One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features. CONCLUSIONS: In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.