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Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

We present the case of a 48-year-old-woman with apparently isolated central nervous system Erdheim-Chester disease characterized by brainstem involvement. Erdheim-Chester disease is extremely rare and multisystem impairment should always be sought in the suspicion of such pathology.

BackgroundThe debate on how to manage women affected by multiple sclerosis (MS) during reproductive age is still open, as is the issue of fertility in such patients. Main issue regard the identification of the optimal window for pregnancy and how to deal with medical therapy before and during conception. The aim of this Delphi consensus was to collect the opinions of a multidisciplinary group, involving reproductive medicine specialists and neurologists with experience in the management of multiple sclerosis women with reproductive desire.MethodsFour experts plus scientific coordinators developed a questionnaire distributed online to 10 neurologists and later discussed the responses and amended a list of statements. The statements were then distributed via an online survey to 23 neurologists (comprising the first 10), who voted on their level of agreement/disagreement with each statement. Consensus was achieved if agreement or disagreement with a statement exceeded 66%.ResultsTwenty-one statements reached consensus after two rounds of voting, leading to the following main recommendations: (1) Fertility evaluation should be suggested to wMS, in case of the need to shorten time to pregnancy and before treatment switch in women on DMTs contraindicated in pregnancy, particularly in case of highly active disease and age > 35 years. (2) ART should not be discouraged in wMS, but the use of DMTs until pregnancy confirmation should be suggested; ART may be considered in order to reduce time to pregnancy in MS women with a reduced ovarian reserve and/or age > 35 years, but in case of an expected poor ART prognosis and the need for more than one ART cycle, a switch to a high-efficacy DMD before ART should be offered. (3) Oocyte cryopreservation may be considered in women with reduced ovarian reserve, with unpredictable time to complete diagnostic workup and achieve disease control; a risk/cost–benefit analysis must be performed in women >35 years, considering the diminished ovarian reserve.ConclusionThis consensus will help MS neurologists to support family planning in wMS, respecting MS therapeutic needs while also taking into account the safety and impact of advancing age on fertility.

We have previously evidenced that Mindfulness Meditation (MM) in experienced meditators (EMs) is associated with long-lasting topological changes in resting state condition. However, what occurs during the meditative phase is still debated. Utilizing magnetoencephalography (MEG), the present study is aimed at comparing the topological features of the brain network in a group of EMs (n = 26) during the meditative phase with those of individuals who had no previous experience of any type of meditation (NM group, n = 29). A wide range of topological changes in the EM group as compared to the NM group has been shown. Specifically, in EMs, we have observed increased betweenness centrality in delta, alpha, and beta bands in both cortical (left medial orbital cortex, left postcentral area, and right visual primary cortex) and subcortical (left caudate nucleus and thalamus) areas. Furthermore, the degree of beta band in parietal and occipital areas of EMs was increased too. Our exploratory study suggests that the MM can change the functional brain network and provides an explanatory hypothesis on the brain circuits characterizing the meditative process.

Mild cognitive impairment (MCI) is a transitional clinical stage prior to dementia. Patients with amnestic MCI have a high risk of progression toward Alzheimer’s disease. Both amnestic mild cognitive impairment and sporadic Alzheimer’s disease are multifactorial disorders consequential from a multifaceted cross-talk among molecular and biological processes. Non-coding RNAs play an important role in the regulation of gene expression, mainly long non-coding RNAs (lncRNAs), that regulate other RNA transcripts through binding microRNAs. Cross-talk between RNAs, including coding RNAs and non-coding RNAs, produces a significant regulatory network all through the transcriptome. The relationship of genes and non-coding RNAs could improve the knowledge of the genetic factors contributing to the predisposition and pathophysiology of MCI. The objective of this study was to identify the expression patterns and relevant lncRNA-associated miRNA regulatory axes in the blood of MCI patients, which includes lncRNA-SNHG16, lncRNA-H19, and lncRNA-NEAT1. Microarray investigations have demonstrated modifications in the expression of long non-coding RNAs (lncRNA) in the blood of patients with MCI compared with control samples. This is the first study to explore lncRNA profiles in mild cognitive impairment blood. Our study proposes RNAs targets involved in molecular pathways connected to the pathogenesis of MCI.

Background: Brain connectome fingerprinting is progressively gaining ground in the field of brain network analysis. It represents a valid approach in assessing the subject-specific connectivity and, according to recent studies, in predicting clinical impairment in some neurodegenerative diseases. Nevertheless, its performance, and clinical utility, in the Multiple Sclerosis (MS) field has not yet been investigated. Methods: We conducted the Clinical Connectome Fingerprint (CCF) analysis on source-reconstructed magnetoencephalography signals in a cohort of 50 subjects: twenty-five MS patients and twenty-five healthy controls. Results: All the parameters of identifiability, in the alpha band, were reduced in patients as compared to controls. These results implied a lower similarity between functional connectomes (FCs) of the same patient and a reduced homogeneity among FCs in the MS group. We also demonstrated that in MS patients, reduced identifiability was able to predict, fatigue level (assessed by the Fatigue Severity Scale). Conclusion: These results confirm the clinical usefulness of the CCF in both identifying MS patients and predicting clinical impairment. We hope that the present study provides future prospects for treatment personalization on the basis of individual brain connectome.

Abstract Background erenumab was safe and effective in clinical trials for the prevention of migraine. However, real-life data are still lacking. Here we report the clinical experience from an Italian real-world setting using erenumab in patients with chronic migraine experiencing previous unsuccessful preventive treatments. Methods Seventy patients with chronic migraine and failure to ≥4 migraine preventive medication classes initially received monthly erenumab 70 mg s.c. Patients without a clinically meaningful improvement, considered as a > 30% reduction in headache days per month, after ≥3 months of therapy switched to monthly erenumab 140 mg. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity and migraine-related disability and impact, and validated questionnaires to explore depression/anxiety, sleep, and quality of life (QoL). Finally, the Pain Catastrophizing Scale, Allodynia Symptom Checklist-12 and MIGraine attacks-Subjective COGnitive impairments scale (MIG-SCOG) were administered. Results 70% of patients were “responders” after the third administration of erenumab 70 mg, whereas 30% switched to erenumab 140 mg; 29% (6 pts) responded after the sixth administration. The headache-day frequency was reduced from 21.1 ± 0.7 to 11.4 ± 0.9 days after the third administration (p

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by functional connectivity alterations in both motor and extra-motor brain regions. Within the framework of network analysis, fingerprinting represents a reliable approach to assess subject-specific connectivity features within a given population (healthy or diseased). Here, we applied the Clinical Connectome Fingerprint (CCF) analysis to source-reconstructed magnetoencephalography (MEG) signals in a cohort of seventy-eight subjects: thirty-nine ALS patients and thirty-nine healthy controls. We set out to develop an identifiability matrix to assess the extent to which each patient was recognisable based on his/her connectome, as compared to healthy controls. The analysis was performed in the five canonical frequency bands. Then, we built a multilinear regression model to test the ability of the “clinical fingerprint” to predict the clinical evolution of the disease, as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r), the King’s disease staging system, and the Milano-Torino Staging (MiToS) disease staging system. We found a drop in the identifiability of patients in the alpha band compared to the healthy controls. Furthermore, the “clinical fingerprint” was predictive of the ALSFRS-r (p = 0.0397; β = 32.8), the King’s (p = 0.0001; β = −7.40), and the MiToS (p = 0.0025; β = −4.9) scores. Accordingly, it negatively correlated with the King’s (Spearman’s rho = -0.6041, p = 0.0003) and MiToS scales (Spearman’s rho = −0.4953, p = 0.0040). Our results demonstrated the ability of the CCF approach to predict the individual motor impairment in patients affected by ALS. Given the subject-specificity of our approach, we hope to further exploit it to improve disease management.

Background: Digital health, including telemedicine, is increasingly recommended for the management of chronic neurological disorders, and it has changed the roles of patients and clinicians. Methods: In this cross-sectional study we aimed to investigate the digital work engagement of Italian neurologists through a survey collected between September 2020 and January 2021. Questionnaires were anonymous and collected demographic characteristics, attitudes towards digital devices and social media, and details about the clinician–patient relationship. We used logistic-regression models to identify characteristics associated with the propensity to communicate with patients using social media. Results: Among the 553 neurologists who participated to the study, smartphones and computers were widely preferred compared with tablets; wearable devices were not common, although some neurologists desired them. A total of 48% of participants reported communicating with patients using social media but only a few were in favor of social friendship with patients; WhatsApp was the social media most popular for professional (86%) and personal (98%) purposes. Propensity to communicate with social media was significantly higher among those who were older ( p

Brain activity during rest displays complex, rapidly evolving patterns in space and time. Structural connections comprising the human connectome are hypothesized to impose constraints on the dynamics of this activity. Here, we use magnetoencephalography (MEG) to quantify the extent to which fast neural dynamics in the human brain are constrained by structural connections inferred from diffusion MRI tractography. We characterize the spatio-temporal unfolding of whole-brain activity at the millisecond scale from source-reconstructed MEG data, estimating the probability that any two brain regions will significantly deviate from baseline activity in consecutive time epochs. We find that the structural connectome relates to, and likely affects, the rapid spreading of neuronal avalanches, evidenced by a significant association between these transition probabilities and structural connectivity strengths (r = 0.37, p

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease, which not only affects physical functioning, but is also associated with cognitive impairments and great psychological distress. The combination of those symptoms may have negative consequences on the family functioning of patients with MS, with detrimental effects on both marital relationships and parental bonding. Furthermore, the presence of individual characteristics and of an adequate social support may also contribute to the quality and endurance of family relationships. Particularly, high levels of alexithymia, a personality trait that affects the recognition of a person's own emotions, have been associated with reduced interpersonal communication skills and enhanced anxiety/depressive symptoms. Therefore, the main aim of the present study is to provide an in-depth evaluation of family functioning and related factors in patients with MS and their families. In order to reach this goal, the perceived quality of family functioning, dyadic relationships, and parental bonding will be first investigated. Secondly, the possible associations between the quality of family relationships and the presence of alexithymia, psychological distress, and perceived social support will be examined. Patients with MS and their families who will consent to take part in the study will be asked to provide sociodemographic and clinical information, and to complete a series of questionnaires, presented and uploaded on an online dedicated platform. The final sample will be made up of 300 families, consecutively recruited from the Italian medical centers involved in the project. The results of the present study will shed light on the family functioning of patients with MS, through a comprehensive assessment of the main factors that are associated with family dynamics. A holistic evaluation of those aspects can help clinicians and researchers understand family dynamics in MS population better.

Introduction: The majority of people diagnosed with MS are of childbearing or child fathering age, therefore family planning is an important issue for both women and men with MS. Fertility and the course of pregnancy are not affected by MS; however, people with MS (pwMS) may have concerns that there will be a greater risk of complications to the mother and/or adverse pregnancy outcomes either due to the disease or to ongoing medication. This survey aimed to understand family planning decision making in pwMS and related unmet educational needs.Methods: A total of 332 pwMS across the USA, UK, France, Germany, Italy, and Spain were recruited from a specialist patient panel agency to participate in a smartphone-enabled standing panel. The 80-question survey focussed on decision making and information sources for pwMS regarding family planning, as well as behavior during and after pregnancy. Male patients with MS did not respond to specific questions on pregnancy. Survey results were directly compared with the 2016 US and 2010 UN census data.Results: pwMS were more likely to have no children than the general population, particularly in the subgroup of patients aged 36–45 years. A total of 56% of pwMS reported that the disease affected, with different degrees of impact, their family planning decision making. Of these, 21% significantly changed their plans for timing of pregnancy and the number of children, and 14% decided against having children. Participants indicated that healthcare professionals were the primary source of information on family planning (81% of responses). The timing of planned pregnancy was not considered when selecting treatment by 78% of participants.Conclusion: MS was found to significantly impact family planning decision making, with pwMS significantly less likely to have children in comparison with the general population.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer’s disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases, there is still no evidence about the possible relationship between executive performances and resting-state brain FC following rTMS in patients with mild cognitive impairment (MCI). In this preliminary study, we aimed to evaluate the possible effects of rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC) in 27 MCI patients randomly assigned to two groups: one group received high-frequency (10 Hz) rTMS (HF-rTMS) for four weeks (n = 11), and the other received sham stimulation (n = 16). Cognitive and psycho-behavior scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status, Beck Depression Inventory-II, Beck Anxiety Inventory, Apathy Evaluation Scale, and brain FC, evaluated by independent component analysis of resting state functional MRI (RS-fMRI) networks, together with the assessment of regional atrophy measures, evaluated by whole-brain voxel-based morphometry (VBM), were measured at baseline, after five weeks, and six months after rTMS stimulation. Our results showed significantly increased semantic fluency (p = 0.026) and visuo-spatial (p = 0.014) performances and increased FC within the salience network (p ≤ 0.05, cluster-level corrected) at the short-term timepoint, and increased FC within the left fronto-parietal network (p ≤ 0.05, cluster-level corrected) at the long-term timepoint, in the treated group but not in the sham group. Conversely, regional atrophy measures did not show significant longitudinal changes between the two groups across six months. Our preliminary findings suggest that targeting DLPFC by rTMS application may lead to a significant long-term increase in FC in MCI patients in a RS network associated with executive functions, and this process might counteract the progressive cortical dysfunction affecting this domain.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

Background: Digital devices and online social networks are changing clinical practice. In this study, we explored attitudes, awareness, opinions, and experiences of neurologists toward social media and digital devices.Methods: Each member of the Italian Society of Neurology (SIN) participated in an online survey (January to May 2018) to collect information on their attitude toward digital health.Results: Four hundred and five neurologists participated in the study. At work, 95% of responders use the personal computer, 87% the smartphone, and 43.5% the tablet. These devices are used to obtain health information (91%), maintain contact with colleagues (71%), provide clinical information (59%), and receive updates (67%). Most participants (56%) use social media to communicate with patients, although 65% are against a friendship with them on social media. Most participants interact with patients on social media outside working hours (65.2%) and think that social media have improved (38.0%) or greatly improved (25.4%) the relationship with patients. Most responders (66.7%) have no wearable devices available in clinical practice.Conclusion: Italian neurologists have different practices and views regarding the doctor–patient relationship in social media. The availability of digital devices in daily practice is limited. The use of social networks and digital devices will increasingly permeate into everyday life, bringing a new dimension to health care. The danger is that advancement will not go hand in hand with a legal and cultural adaptation, thus creating ambiguity and risks for clinicians and patients. Neurologists will need to be able to face the opportunities and challenges of this new scenario.

BackgroundFamily functioning relies on different factors that are related to the individual characteristics of each member, the social context in which the family nucleus is integrated, and the internal and interpersonal family factors. The Short Version of the Family Assessment Measure-III, Dyadic Adjustment Scale, Inventory of Parent and Peer Attachment, Twenty-item Toronto Alexithymia Scale, Hospital Anxiety and Depression Scale, and Multidimensional Scale of Perceived Social Support are among the most commonly employed self-report measures for the assessment of family functioning and related factors. Traditionally, these scales have been administered using paper-and-pencil versions. However, with increased access to the Internet, online administration of questionnaires has become more common. The present study aimed to validate an online version of each of the above-mentioned questionnaires in a heterogeneous sample of Italian healthy individuals.MethodsOne-hundred participants were recruited for each questionnaire. A crossover design was used in each validation. The minimum important difference (MID) was applied to evaluate the differences in the variances of the paper-and-pencil and online format scores. A MID >0.5 is a reasonable first approximation of a threshold of important change. Taking into account the cross over design, mean difference between pencil-and-paper and online versions, and Intraclass Correlation Coefficient were also estimated by mixed models.ResultsThe MID was

Social cognition includes mental operations essential for functional social interactions, and several studies revealed an impairment of social cognition abilities in patients with Multiple Sclerosis (MS). These deficits have been related to global and focal gray matter atrophy as well as microstructural white matter damage. Although some studies reveal a correlation between social cognition and task-based functional magnetic resonance imaging (MRI), no studies to date have explored the association between brain resting-state functional connectivity (RS-FC) abnormalities and several measures of social cognition in MS. The aim of this explorative study was to assess the contribution of RS-FC abnormalities of major brain networks to social cognition in MS patients. Clinical, neuropsychological, and MRI data were collected from 41 non-depressed and cognitively preserved relapsing-remitting MS patients (mean disease duration = 8.8 ± 8.2 years; median Expanded Disability Status Scale = 1.5, range 0–6.5) and 25 matched healthy controls (HCs). The ToM Pictures Sequencing Task (TMPS) and the Reading the Mind in the Eyes Task were employed to evaluate social cognition. All participants underwent a structural MRI and RS functional MRI 3T protocol. Regional gray matter atrophy was measured, and FCs of the default mode (DMN), right and left fronto-parietal, executive (EN), salience, cerebellar, and limbic (LN) networks were evaluated by independent component analysis (ICA). Differences on TMPS were found between MS patients and HC (MS < HC). In the MS group, associations were found between right middle temporal gyrus FC (in the DMN) and reciprocity subscale of TMPS, posterior cingulate cortex (PCC) FC (in the DMN) and first-order false-belief subscale of TMPS, cingulate gyrus FC (in the EN) and TMPS as well as reciprocity subscale of TMPS, and right superior temporal gyrus (in the LN) and reciprocity subscale of TMPS. All detected RS-FC changes did not co-localize with regional gray matter atrophy. The results suggest an association between social cognition and RS-FC changes of DMN, EN, and LN in MS. Future studies should further explore the possible adaptive or maladaptive mechanisms of these FC abnormalities in MS.

Background: Patients with multiple sclerosis (MS) are considered at higher risk of COVID-19 infection due to treatment with immune modulators and immune-suppressive agents. The exact risk factors are not clear. So, we aimed to conduct a study to determine the predictors of catching COVID-19 infection during the pandemic stage in patients with multiple sclerosis (MS). Methods: We conducted a multicenter screening study and developed an online questionnaire to collect patients' self-reported demographic features along with MS-related and COVID-19–related information. The online questionnaire link was released by the Iran Multiple Sclerosis Society (IMSS) social media channel, accessible for 4160 MS patients totally and also was sent by WhatsApp for nonmember cases. Results: Totally, 1448 MS patients participated in our study. Twenty-five (1.7%) patients were diagnosed with COVID-19, from which 4 were hospitalized, 4 were treated with medical therapy, and 17 patients had home-quarantine. The patients with COVID-19 diagnosis were more frequently treated with rituximab (28% vs 24%, P = 0.001) than others, and cardiovascular comorbidity was more frequent in this group (8% vs 1.6%, P = 0.01). Regression analysis showed that cardiovascular disease was a significant positive predictor of COVID-19 infection (OR = 5.2, 95% CI: 1.1–23.7). Conclusions: Patients with MS who have cardiovascular disease should be more monitored for COVID-19 infection as they are at higher risk of infection.

Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders.Aims: The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified.Methods: Participants were consenting adults with SPMS since ≤5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs.Results: Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany (p = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28–35% obtained second opinions, and 48–56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy (p < 0.001).Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13–0.78 for Central Italy; OR 0.21, 95% CI 0.08–0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47–41.37 for dependent vs. autonomous patients).All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: “physiotherapy” and “active patient care involvement.” The other two differed across countries: “an individualized health care plan” and “information on social rights and policies” in Italy, and “psychological support” and “cognitive rehabilitation” in Germany.Conclusions: Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries.

Phrenic nerve palsy (PNP) is a well-known complication of cardiac surgery or jugular/subclavian vein catheterization, presenting with cough, hiccups, dyspnoea/shortness of breath and, in some cases, ventilatory failure. Rarely, PNP is a complication of transcatheter radiofrequency ablation for atrial fibrillation. This report describes the case of a 72-year-old woman with a 2-year history of recurrent paroxysmal atrial fibrillation associated with occasional palpitations and shortness of breath who underwent routine transcatheter radiofrequency ablation. Three days after the procedure, the patient developed shortness of breath and progressive dyspnoea. Motor nerve conduction showed the absence of the right phrenic nerve compound motor action potential compared with the normal left side confirming the diagnosis of a right phrenic nerve palsy. This current case demonstrated the importance of undertaking an electrophysiological evaluation of phrenic nerve conduction after transcatheter radiofrequency ablation in patients presenting with palpitations and shortness of breath even if present a few days after the procedure.

Background: Public engagement (PE) is defined as the involvement of “specialists who listen, develop their understanding, and interact with non-specialists in non-profit activities of educational, cultural, and social nature to engage the public in science-related matters”. The public health relevance of PE consists in building up a scientifically literate society, able to participate in and support scientific and technological developments and their implications for educational settings. Neurological disorders account for 35% of all diseases. PE could have a positive impact on the lives of people affected by neurological diseases. Method: This review evaluates the role of PE in dementia, stroke, epilepsy, multiple sclerosis, Parkinson’s disease, migraine, neurogenetics, and amyotrophic lateral sclerosis. Results and Conclusions: PE can provide accessible information, support research activities and prevention through appropriate lifestyles, and increase knowledge and awareness of neurological disorders, improving their diagnosis and treatment.

Multiple sclerosis (MS) is the most common neurological disorder in young adults. The prevalence of walking impairment in people with MS (pwMS) is estimated between 41% and 75%. To evaluate the walking capacity in pwMS, the patient reported outcomes (PROs) and performance-based tests (i.e., the 2-minute walk test, the 6-minute walk test, the Timed 25-Foot Walk Test, the Timed Up and Go Test, and the Six Spot Step Test) could be used. However, some studies point out that the results of both performance-based tests and objective measures (i.e., by accelerometer) could not reflect patient reports of walking performance and impact of MS on daily life. This review analyses different motion sensors embedded in smartphones and motion wearable device (MWD) that can be useful to measure free-living walking behavior, to evaluate falls, fatigue, sedentary lifestyle, exercise, and quality of sleep in everyday life of pwMS. Caveats and limitations of MWD such as variable accuracy, user adherence, power consumption and recharging, noise susceptibility, and data management are discussed as well.

The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients.We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis.During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41, p

Magnetic Resonance Imaging (MRI) techniques provided evidences into the understanding of cognitive impairment (CIm) in Multiple Sclerosis (MS).To investigate the role of white matter (WM) and gray matter (GM) in predicting long-term CIm in a cohort of MS patients.303 out of 597 patients participating in a previous multicenter clinical-MRI study were enrolled (49.4% were lost at follow-up). The following MRI parameters, expressed as fraction (f) of intracranial volume, were evaluated: cerebrospinal fluid (CSF-f), WM-f, GM-f and abnormal WM (AWM-f), a measure of lesion load. Nine years later, cognitive status was assessed in 241 patients using the Symbol Digit Modalities Test (SDMT), the Semantically Related Word List Test (SRWL), the Modified Card Sorting Test (MCST), and the Paced Auditory Serial Addition Test (PASAT). In particular, being SRWL a memory test, both immediate recall and delayed recall were evaluated. MCST scoring was calculated based on the number of categories, number of perseverative and non-perseverative errors.AWM-f was predictive of an impaired performance 9 years ahead in SDMT (OR 1.49, CI 1.12-1.97 p = 0.006), PASAT (OR 1.43, CI 1.14-1.80 p = 0.002), SRWL-immediate recall (OR 1.72 CI 1.35-2.20 p

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Resting State fMRI (RS-fMRI) represents an emerging and powerful tool to explore brain functional connectivity (FC) changes associated with neurologic disorders. Compared to activation/task-related fMRI, RS-fMRI has the advantages that (i) BOLD fMRI signals are self-generated and independent of subject’s performance during the task and (ii) a single dataset is sufficient to extract a set of RS networks (RSNs) that allows to explore whole brain FC. According to these features RS-fMRI appears particularly suitable for the study of FC changes related to multiple sclerosis (MS). In the present review we will first give a brief description of RS-fMRI methodology and then an overview of most relevant studies conducted so far in MS by using this approach. The most interesting results, in particular, regard the default-mode network (DMN), whose FC changes have been correlated with cognitive status of MS patients, and the visual RSN (V-RSN) whose FC changes have been correlated with visual recovery after optic neuritis. The executive control network (ECN), the lateralized frontoparietal network (FPN), and the sensory motor network (SMN) have also been investigated in MS, showing significant FC rearrangements. All together, RS-fMRI studies conducted so far in MS suggest that prominent RS-FC changes can be detected in many RSNs and correlate with clinical and/or structural MRI measures. Future RS-fMRI studies will further clarify the dynamics and clinical impact of RSNs changes in MS.