The Contribution of Neuroimaging to the Understanding of Essential Tremor Pathophysiology: a Systematic Review

Essential tremor (ET) is one of the most common movement disorders. Over the last 10 years, magnetic resonance imaging (MRI) has shed light on the structural and functional abnormalities possibly involved in ET pathophysiology. In this systematic review, we aimed to identify the cortical and subcortical structures involved and the role that different brain areas play in the pathophysiology of motor and non-motor ET features. We found that structural (grey and white matter) cerebellar damage and connectivity alterations between the cerebellum and various cortical areas play a role in both motor and non-motor symptoms of ET. In particular, many studies found an association between MRI findings and non-motor symptoms

Abnormal salivary total and oligomeric alpha-synuclein in Parkinson's disease

In Parkinson’s disease (PD), alpha-synuclein (a-syn) can be detected in biological fluids including saliva. Although previous studies found reduced a-syn total (a-syntotal) concentration in saliva of PD patients, no studies have previously examined salivary a-syn oligomers (a-synolig) concentrations or assessed the correlation between salivary a-syntotal, a-synolig and clinical features in a large cohort of PD patients. Is well known that a-synolig exerts a crucial neurotoxic effect in PD. We collected salivary samples from 60 PD patients and 40 age- and sex-comparable healthy subjects. PD was diagnosed according to the United Kingdom Brain Bank Criteria. Samples of saliva were analyzed by specific anti-a-syn and anti-oligomeric a-syn ELISA kits. A complete clinical evaluation of each patient was performed using MDS-Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Montreal Cognitive Assessment and Frontal Assessment Battery. Salivary a-syntotal was lower, whereas a-synolig was higher in PD patients than healthy subjects. The a-synolig/a-syntotal ratio was also higher in patients than in healthy subjects. Salivary a-syntotal concentration negatively correlated with that of a-synolig and correlated with several patients’ clinical features. In PD, decreased salivary concentration of a-syntotal may reflect the reduction of a-syn monomers (a-synmon), as well as the formation of insoluble intracellular inclusions and soluble oligomers. The combined detection of a-syntotal and a-synolig in the saliva might help the early diagnosis of P

Common and rare variants in TMEM175 gene concur to the pathogenesis of Parkinson’s Disease in Italian patients

Parkinson’s disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused the attention on the common and rare variants identified in the lysosomal K+ channel TMEM175. The study includes a detailed clinical and genetic analysis of 400 cases and 300 controls. Molecular studies were performed on patient-derived fibroblasts. The functional properties of the mutant channels were assessed by patch-clamp technique and co-immunoprecipitation. We have found that TMEM175 was highly expressed in dopaminergic neurons of the substantia nigra pars compacta and in microglia of the cerebral cortex of the human brain. Four common variants were associated with PD, including two novel variants rs2290402 (c.-10C > T) and rs80114247 (c.T1022C, p.M341T), located in the Kozak consensus sequence and TM3II domain, respectively. We also disclosed 13 novel highly penetrant detrimental mutations in the TMEM175 gene associated with PD. At least nine of these mutations (p.R35C, p. R183X, p.A270T, p.P308L, p.S348L, p. L405V, p.R414W, p.P427fs, p.R481W) may be sufficient to cause the disease, and the presence of mutations of other genes correlated with an earlier disease onset. In vitro functional analysis of the ion channel encoded by the mutated TMEM175 gene revealed a loss of the K+ conductance and a reduced channel affinity for Akt. Moreover, we observed an impaired autophagic/lysosomal proteolytic flux and an increase expression of unfolded protein response markers in patient-derived fibroblasts. These data suggest that mutations in TMEM175 gene may contribute to the pathophysiology of PD

EU Health Union in a digital environment, between fight against fake medicines, shortage prevention, and data protection

Dopo la pandemia da Covid-19, l’EU ha dato avvio all’Unione Europea della Salute finalizzata a prevenire e rsipondere alle crisi sanitarie, assicurando disponibilità di dispositivi medici affidabili e innovativi e gestendo i dati sanitari. L’Unione Europea della Salute è strettamente interconnessa con lo sviluppo digitale, soprattutto per l’uso dell’intelligenza artificiale nell’offerta di servizi e prodotti sanitari, ma anche in riferimento alla digitalizzazione delle catene di approvvigionamento dei prodotti sanitari e alla raccolta, condivisione ed uso dei dati nello Spazio Europeo dei Dati Sanitari. I temi in parola sono significativamente influenzati dalla disciplina elaborata dalle Istituzioni dell’UE per i servizi digitali, in particolare il Digital Service Act (DSA) e l’AI Act (AIA). Assumendo le catene di approvvigionamento dei prodotti sanitari e la gestione dei dati come casi studio, il paper analizza l’impatto della digitalizzazione sull’Unione Europea della Salute alla luce della disciplina dei servizi digitali in termini di rischi e opportunità. Sotto il profilo dei rischi, il paper si focalizza sulla vendita on line dei farmaci fake (falsificati o contraffatti) e sul contributo del DSA all’identificazione e rimozione di tali prodotti. Il paper si focalizza, altresì, sui limiti riscontrati dai ricercatori nell’accesso ai dati sanitari sulle piattaforme on line e sugli obblighi imposti dall’art. 40 DSA. Per quanto riguarda le opportunità, il paper di focalizza sul potenziale uso dell’intelligenza artificiale nella gestione dell’approvvigionamento dei prodotti sanitari, per verificare il suo contributo in termini di efficienza e buon funzionamneto del sistema di prevenzione e gestione delle crisi creato dalla Commissione europea e dalle Agenzie. Il paper analizza, altresì, l’impatto dell’intelligenza artficiale sulla raccolta, condivisione e uso dei dati sanitari. Il paper giunge alla conclusione che solo una adeguata regolazione orientata alla prenzione e gestione del rischio e delle emergenze può realizzare il giusto bilanciamento tra pericoli e opportunità derivanti dalle nuove tecnologie nel settore sanitario. In questa prospettiva, la Commissione europea e le Agenzie sembrano il livello ottimale di standardizzazione per assicurare una digitalizzazione sicura ed efficace dello spazio digitale.After the Covid-19 pandemic, the EU launched the European Health Union (EHU) aimed at preparing and responding to health crises, assuring availability of affordable and innovative medical supplies, and managing the health data. The EHU is strictly interconnected with the digital development, mainly as it concerns the Artificial Intelligence (AI) use in health service provision and medical good production, but also as it concerns the digitalization of medical product supply chains and of heath data collecting, sharing, and use in European Health Data Space. These issues are being significantly impacted by the discipline elaborated by the EU Institutions to regulate the sale of goods and services on the digital platforms, more specifically the by the Digital Service Act (DSA) 1 and the Artificial Intelligence Act (AIA). Assuming the medical supply chains and data management as case-studies, the paper analyzes the digitalization impact on the EHU in the light of digital service rules in terms of risks and opportunities. As it concerns risks, fistly, the paper focuses on the phenomenon of the online sale of fake (falsified of counterfeit) medicines and on the contribution offered by DSA in the identification and remotion of such products. Secondly, the paper analyses the limits currently faced by the researchers to the access to the health data on online platforms and the obligations imposed by the Article 40 DSA. As it concerns opportunities, firstly, the paper analyzes the potential AI use in the supply management of medical goods, with specific attention to the joint procurement procedures and stockpile assessment and management, in order to verify its contribution in terms of effectiveness and well- functioning of the crisis preparedness, prevention, and management system created by the European Commissions and European agencies. Secondly, the paper analyzes the AI impact on the collecting, sharing, and use of health data. Paper arrives at the conclusion that only a proper regulation oriented to risk and crisis prevention and management could determine the right balance between threats and opportunities coming from new technologies in the health sector. In this perspective, the European Commission and EU Agencies’ appears the “optimum standard-setting level” to improve an effective and sure health space digitalization

Iron metabolism and its detection through MRI in parkinsonian disorders: a systematic review

Iron deposition in the brain normally increase with age, but its accumulation in certain regions is ob- served in a number of neurodegenerative diseases in- cluding Parkinson’s disease (PD) and other parkinson- isms. Whether iron overload leads to dopaminergic neu- ronal death in the SN of PD patients or is instead sim- ply a by-product of the neurodegenerative progression is still yet to be ascertained. Magnetic resonance imaging (MRI) is a non-invasive method to assess brain iron content in PD patients. In PD, accurate radiologic visu- alization of basal ganglia is required. Deep gray matter nuclei are well presented in T2- and T2*-weighted im- ages. T2*-weighted gradient-echo (GRE) is widely used to assess calcifications and also for iron detection. On the other hand, new methods specifically designed for detecting iron-induced susceptibility differences can be further improved by sequences like susceptibility- weighted imaging (SWI). In the present review, we aim to summarize the available data on brain iron de- position in PD

Parkinsonian patients and poor awareness of dyskinesias.

[No abstract available

Serotonin toxicity: a short review of the literature and two case reports involving Citalopram

The serotonin toxicity (ST) is a potentially life-threatening adverse drug reaction results from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs. ST can be caused by a single or a combination of drugs with serotonergic activity due to excessive serotonergic agonism on central nervous system and peripheral serotonergic receptors (monoamine oxidase inhibitors, tricyclic antidepressants, SSRIs, opiate analgesics, over-the-counter cough medicines, antibiotics, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse, H2-antagonist and herbal products). The serotonin toxicity is often described as a clinical triad of mental-status changes (agitation and excitement with confusion), autonomic hyperactivity (diaphoresis, fever, tachycardia, and tachypnea), neuromuscular abnormalities (tremor, clonus, myoclonus, and hyperreflexia) and, in the advanced stage, spasticity; not all of these findings are consistently present. In this article, we describe two cases of ST due to interaction between Citalopram and two CYP2D6 inhibitors: Cimetidine and Topiramate and their clinical resolution after treatment discontinuation