Multiple sclerosis (MS) is an autoimmune pathology leading to neurodegeneration. Because of the complexity and heterogenic etiology of this disease, diagnosis and treatment for individual patients are challenging. Exosome-associated microRNAs (miRNAs) have recently emerged as a new class of diagnostic biomarkers involved in both autoimmune and neurologic disorders. Interesting new evidence has emerged showing that circulating miRNAs are dysregulated in MS body fluids, including serum, plasma, and cerebrospinal fluid. We hypothesized that exosome-associated miRNAs could present a readily accessible blood-based assay for MS disease. We detected expression of miRNAs by quantitative PCR on a small cohort of MS patients. We analyzed circulating exosome-associated miRNAs of MS patients before and after therapy and found that 14 exosome-associated miRNAs were significantly down-regulated, while 2 exosome-associated miRNAs were significantly up-regulated in IFN-β-treated relapsing-remitting MS patients with response to therapy compared to those without response. We identified a serum miRNA panel that could be used to monitor the response to IFN-β therapy. Overall, these data suggest that circulating exosome-associated miRNA profiling could represent an easily detectable biomarker of disease and treatment response.-Manna, I., Iaccino, E., Dattilo, V., Barone, S., Vecchio, E., Mimmi, S., Filippelli, E., Demonte, G., Polidoro, S., Granata, A., Scannapieco, S., Quinto, I., Valentino, P., Quattrone, A. Exosome-associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients.

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ObjectiveCognitive deficits are common in Parkinson’s disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease.MethodsSerum IGF-1 levels were determined in 405 early, drug-naïve PD patients and 191 healthy controls (HC) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis.ResultsIGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (β = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (β = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (β = -0.05, 95%CI: -0.09 to -0.009, p = 0.019).ConclusionsLower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.

Background and purpose Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor‐dominant versus postural instability and gait disorder; (ii) tremor‐dominant versus akinetic‐rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow‐up period of 4 years. Methods Newly diagnosed, untreated PD patients were classified as tremor‐dominant versus postural instability and gait disorder and tremor‐dominant versus akinetic‐rigid at baseline and after 2 and 4 years. Results There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4‐year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2‐ to 4‐year follow‐up. Conclusions The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor‐dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.

Sir, On January 30, 2020, the World Health Organization (WHO) declared the emergence of a novel coronavirus (here named COVID-19), firstly reported few weeks earlier in Wuhan, Hubei Province of China, as a public health emergency of international concern. Since then, drastic countermeasures including shutdowns of public services have been implemented worldwide to reduce virus transmission: on March 9, 2020, the Italian Prime Minister imposed a national lockdown and ordered all hospitals to stop all non-urgent medical procedures, further aiming to release medical capacities for the management of COVID-19-infected patients. Botulinum neurotoxin (BoNT) is a neurotoxic protein produced by the bacterium Clostridium botulinum, which is used in medical practice with a number of different indications including spasticity, dystonia, and chronic migraine [1]. As BoNT injections are usually given every 3 to 4 months, a large number of patients missed their scheduled treatment during the lockdown. Two initial reports described a significant worsening of this group of patients [2, 3], highlighting the importance of BoNT treatment in the management of these chronic conditions. However, these results arose from uncontrolled studies [2, 3]. We here report the results of a case-control study about the effects of the BoNT outpatient clinic shutdown on its patients and their health-related quality of life (HRQoL). Soon after the ease of the lockdown restrictions in Italy on May 4, 2020, our center offered one BoNT extra-clinic per week to reschedule all willing patients who had missed their appointment because of the service shutdown (from here on named "cases"). Patients attending the BoNT service with their usual schedule in the same period served as controls.