Giulia Giannini

Overexpression of blood microRNAs 103a, 30b, and 29a in l-dopa–treated patients with PD

Objective: The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from l-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context. Methods: We analyzed RNAs from peripheral blood of 36 l-dopa–treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription–quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation. Results: Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis. Conclusions: We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after l-dopa administration are necessary to define the involvement of l-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential.

Migraine and sleep disorders

The burden of migraine strongly increases, considering its linkage with sleep disorders. Migraine is positively associated with many sleep-complaint disorders; some are confirmed by several studies, such as restless leg syndrome, whereas others still remain uncertain or controversial, e.g. narcolepsy. Many studies have investigated the association between headache and other sleep disturbances such as daytime sleepiness, insomnia, snoring and/or apnea, but only a few have focused on migraine. Highlighting the comorbidity between migraine and sleep disorders is important to improve treatment strategies and to extend the knowledge of migraine pathophysiology.

Association between restless legs syndrome and migraine: A population-based study

A higher prevalence of restless legs syndrome (RLS) in migraineurs has been reported in clinical samples and in two large‐scale clinical trials performed on healthcare workers but general population‐based studies on this topic are lacking. The aim of this study was to assess the association between migraine and RLS in an Italian rural adult population‐based setting.

Association between restless legs syndrome and hypertension: A preliminary population-based study in South Tyrol, Italy

Restless legs syndrome (RLS) is a sleep‐related movement disorder characterized by an irresistible urge to move the legs accompanied by paresthesia and/or dysesthesia that begins or worsens in the evening and night and that is partially or totally relieved by movement. Many studies have investigated the association between RLS and cardiovascular risk factors, particularly hypertension, leading to conflicting results. The aim of this study was to assess the association between RLS and hypertension considering also other cardiovascular risk factors that could act as confounders.

Nociception and autonomic nervous system.

The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Pain may also be experienced in absence of noxious stimuli and together with temperature and other bodily feelings constitute the interoception redefined as the sense of the physiological condition of the entire body, not just the viscera. The main characteristic of these feelings is the affective aspect. Emotion, motivation, and consequent behavior connected with these feelings characterize their homeostatic role. This implies an interaction between neural structures involved in pain sensation and autonomic control. The aim of this review is to focus on pain perception, mainly on pain matrix structures’ connections with the autonomic nervous system.

Early stridor onset and stridor treatment predict survival in 136 patients with MSA

Objective: To evaluate the predictive value of stridor and its latency of onset and to investigate the role of stridor treatment in a cohort of patients with multiple system atrophy (MSA) referred to a tertiary center. Methods: We retrospectively identified patients diagnosed with MSA referred to our department beginning in 1991 and evaluated at least yearly during the disease course. Stridor was defined as present when confirmed by a whole night video-polysomnography and as early if presenting within 3 years of disease onset. Survival data, from disease onset to time of death, were calculated with Kaplan-Meier curves. Predictors were identified in univariate and multivariable Cox regression analyses. Results: We included 136 patients with MSA; 113 were deceased at the time of study. Stridor was diagnosed in 42 patients, and 22 presented early stridor onset. Twelve of the 31 patients treated for stridor received tracheostomy, and 19 received continuous positive airway pressure. Overall survival did not differ between patients with and without stridor, while patients with early stridor onset had a worse prognosis than those developing this symptom later. In the stridor subgroup, early stridor onset was an unfavorable survival predictor. Stridor treatment was significantly associated with survival in our population. The Kaplan-Meier curve did not reveal significant differences in survival between the 2 treatments even though there was a trend toward longer disease duration in patients receiving tracheostomy. Conclusions: Our results demonstrated that early stridor onset is an independent predictor for shorter survival and that tracheostomy could control stridor, influencing disease duration.

Migraine: risk factor and comorbidity

The burden of migraine strongly increases considering its linkage with other psychiatric, neurological, cardiovascular and cerebrovascular diseases. Migraine is positively associated with many disorders: some are confirmed by several studies whereas others remain uncertain or controversial. The association with some disorders is not simply due to concomitance but it implies a linkage in terms of causality. Highlighting these relationships is important to improve treatment strategies, broaden our knowledge of the pathophysiology and understand if migraine is per se a modifiable risk factor for some disorders.

The Treatment of Sleep Disorders in Parkinson’s Disease: From Research to Clinical Practice

Sleep disorders (SDs) are one of the most frequent non-motor symptoms of Parkinson’s disease (PD), usually increasing in frequency over the course of the disease and disability progression. SDs include nocturnal and diurnal manifestations such as insomnia, REM sleep behavior disorder, and excessive daytime sleepiness. The causes of SDs in PD are numerous, including the neurodegeneration process itself, which can disrupt the networks regulating the sleep–wake cycle and deplete a large number of cerebral amines possibly playing a role in the initiation and maintenance of sleep. Despite the significant prevalence of SDs in PD patients, few clinical trials on SDs treatment have been conducted. Our aim is to critically review the principal therapeutic options for the most common SDs in PD. The appropriate diagnosis and treatment of SDs in PD can lead to the consolidation of nocturnal sleep, the enhancement of daytime alertness, and the amelioration of the quality of life of the patients.

Migraine and cardiovascular diseases

Migraine has complex relationships with cerebrovascular and cardiovascular disorders but also with cardiac anomalies. Patients affected by migraine with aura have an increased prevalence of right-to-left shunt due to patent foramen ovale or pulmonary arteriovenous malformations. The association between ischemic heart disease, cardiovascular mortality and migraine remains unsettled. The debate focuses on a physiopathological link between migraine and cardiovascular diseases or a higher prevalence of risk factors in migraineurs.

Plasma and White Blood Cells Show Different miRNA Expression Profiles in Parkinson’s Disease

Parkinson’s disease (PD) diagnosis is based on the assessment of motor symptoms, which manifest when more than 50% of dopaminergic neurons are degenerated. To date, no validated biomarkers are available for the diagnosis of PD. The aims of the present study are to evaluate whether plasma and white blood cells (WBCs) are interchangeable biomarker sources and to identify circulating plasma-based microRNA (miRNA) biomarkers for an early detection of PD. We profiled plasma miRNA levels in 99 l-dopa-treated PD patients from two independent data collections, in ten drug-naïve PD patients, and in unaffected controls matched by sex and age. We evaluated expression levels by reverse transcription and quantitative real-time PCR (RT-qPCR) and combined the results from treated PD patients using a fixed effect inverse-variance weighted meta-analysis. We revealed different expression profiles comparing plasma and WBCs and drug-naïve and l-dopa-treated PD patients. We observed an upregulation trend for miR-30a-5p in l-dopa-treated PD patients and investigated candidate target genes by integrated in silico analyses. We could not analyse miR-29b-3p, normally expressed in WBCs, due to the very low expression in plasma. We observed different expression profiles in WBCs and plasma, suggesting that they are both suitable but not interchangeable peripheral sources for biomarkers. We revealed miR-30a-5p as a potential biomarker for PD in plasma. In silico analyses suggest that miR-30a-5p might have a regulatory role in mitochondrial dynamics and autophagy. Further investigations are needed to confirm miR-30a-5p deregulation and targets and to investigate the influence of l-dopa treatment on miRNA expression levels.