Physical Exercise Moderates the Effects of Disability on Depression in People with Multiple Sclerosis during the COVID-19 Outbreak

Physical disability impacts psychosocial wellbeing in people with multiple sclerosis. However, the role of physical activity in this context is still debated. By taking advantage of a previous survey, conducted online from 22 April to 7 May 2020, we performed a post-hoc analysis with the aim to assess the associations between disability, physical exercise, and mental health in multiple sclerosis. We retrieved the following data: (i) sociodemographic information, (ii) changes in lifestyle (including exercise), (iii) physical disability, as measured with the Patient-Determined Disease Steps scale, and (iv) anxiety feelings and depressive symptoms assessed via the items included in the Quality of Life in Neurological Disorders measurement system. Examination of the interaction plot showed that the effect of disability on depression, but not on anxious symptoms, was significant for all levels of physical exercise (low: b = 1.22, 95% C.I. 0.85, 1.58, p < 0.001; moderate: b = 0.95, 95% C.I. 0.66, 1.24, p < 0.001; and high: b = 0.68, 95% C.I. 0.24, 1.13, p = 0.003). Based on these data, we can conclude that disability significantly impacted depression during the COVID-19 pandemic, with physical activity playing a moderating role. Our results suggest that favoring exercise in multiple sclerosis (MS) would ameliorate psychological wellbeing regardless of the level of physical disability

Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study

Background: Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine. Methods: Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine. Results: We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients' age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (p < 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis. Conclusions: Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients

Asymptomatic bradycardia after first fingolimod dose in a pediatric patient with multiple sclerosis - a case report

Fingolimod is currently approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of pediatric patients with relapsing-remitting multiple sclerosis (RRMS). However, transient asymptomatic bradycardia with treatment initiation has been reported in a small population of predisposed patients, which may be a result of short-term activation and internalization/desensitization of the G-protein-gated potassium channel IKACh on the atrial myocyte membrane. Asymptomatic bradycardia, with or without atrioventricular block, is generally self-limiting and has been reported within the first 6 h of administration of the first oral dose of fingolimod. Therefore, patients initiating fingolimod treatment are monitored for this initial period to identify any changes in their electrocardiogram and heart rate that may require further treatment. Here, we report a case of a 17-year-old female with RRMS who received her first fingolimod dose and showed asymptomatic bradycardia that resolved without treatment

Digital Technology in Clinical Trials for Multiple Sclerosis: Systematic Review

Clinical trials in multiple sclerosis (MS) have been including digital technology tools to overcome limitations in treatment delivery and disease monitoring. In March 2020, we conducted a systematic search on pubmed.gov and clinicaltrials.gov databases (with no restrictions) to identify all relevant published and unpublished clinical trials, in English language, including MS patients, in which digital technology was applied. We used "multiple sclerosis" and "clinical trial" as the main search words, and "app", "digital", "electronic", "internet" and "mobile" as additional search words, separately. Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Digital technology has been used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms (e.g., electronic recording of motor performance). Other clinical trials have been using digital technology for monitoring symptoms that would be otherwise difficult to detect (e.g., fatigue, balance), for measuring treatment adherence and side effects, and for self-assessment purposes. Collection of outcome measures is progressively shifting from paper-based on site, to internet-based on site, and, in the future, to internet-based at home, with the detection of clinical and treatment features that would have remained otherwise invisible. Similarly, remote interventions provide new possibilities of motor and cognitive rehabilitation

A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis

Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results. Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = −8.54; 95%CI = −15.51, −1.57; and Coeff = −0.11; 95%CI = −0.20, −0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. Conclusions. In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function

The Framingham cardiovascular risk score and 5-year progression of multiple sclerosis

Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10-year risk of developing macrovascular disease

Predictors of Nabiximols (Sativex®) discontinuation over long-term follow-up: a real-life study

Nabiximols is an effective treatment for spasticity in MS. However, treatment discontinuation over-time might occur and predictors of sustained treatment persistence over long-term follow-up in real-world settings are highly needed. We aim at evaluating baseline predictors of treatment persistence on Nabiximols. This is a retrospective real-world study including MS patients treated with Nabiximols. At baseline (Nabiximols prescription), we evaluated disability using the EDSS, and cognitive function using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Nabiximols discontinuation was evaluated after 4 weeks of treatment ("titration phase''), and over the follow-up ("treatment phase"). We included 396 MS patients (228 females and 168 males). After 4 weeks (titration phase), 266 MS patients (67.2%) were considered persistent on treatment, while 130 patients dropped out. After 19 ± 21 months (treatment phase), 136 out of 266 MS patients (51.1%) were still on treatment, whereas 130 patients dropped at follow-up. Higher EDSS and cognitive impairment predicted treatment discontinuation at follow-up (p = 0.04 and p = 0.005, respectively). In conclusion, higher physical and cognitive disability predicted Nabiximols treatment discontinuation over 2 years in MS patients suffering from spasticity. Nabiximols should be started earlier to decrease the likelihood of treatment discontinuation over time

Peripapillary Vessel Density as Early Biomarker in Multiple Sclerosis

Background:To evaluate retinal vessel density (VD) in macular and in peripapillaryregions in patients with recent onset of multiple sclerosis, at initial demyelinating event(IDE) and in matched relapsing-remitting multiple sclerosis (RRMS) patients.Methods:We evaluated VD in superficial capillary plexus, deep capillary plexus,choriocapillaris and radial peripapillary capillary plexus in IDE, RRMS patients and inmatched healthy controls (HCs) through Optical Coherence Tomography Angiography(OCT-A). Clinical history, including history of optic neuritis, Expanded Disability Statusscale and disease duration of patients were collected.Results:Thirty patients (20 with IDE and 10 with RRMS) and 15 HCs were enrolled. IDEpatients showed a lower VD in radial peripapillary capillary plexus compared with controls(coeff.β= −3.578;p=0.002). RRMS patients displayed a lower VD in both superficialcapillary plexus and radial peripapillary capillary plexus compared with HCs (coeff.β=−4.955;p=0.002, and coeff.β= −7.446;p<0.001, respectively). Furthermore, RRMSpatients showed a decreased VD in radial peripapillary capillary plexus compared withIDE patients (coeff.β= −3.868;p=0.003).Conclusions:Peripapillary region vessel density reduction, revealed through OCT-A,might be considered as an early event in MS, and might be relevant as a biomarker ofdisease pathology

COVID-19 pandemic and mental distress in Multiple Sclerosis: implications for clinical management

BACKGROUND: in multiple sclerosis (MS), disease-related factors and dysfunctional coping might favour the development of mental distress induced by COVID-19 containment measures.METHODS: we explored the relationship between mental distress, disability and coping strategies in the Italian MS population under lockdown. Structural equation modeling (SEM) was applied to information collected via web-survey to identify modifiable factors that could account for mental distress.RESULTS: 845 subjects (497 MS and 348 controls) were included in the study. MS patients showed higher scores than controls for depression (p=0.005), but not for anxiety, emotional dyscontrol or sleep disturbances. The SEM explained 74% of the variance observed in depression score. Within the model, three latent factors were characterized from measured variables: motor disability and cognitive dysfunction contributed to disability (beta=0.509 and beta=0.836, p<0.001); positive attitude and exercise contributed to active attitude (beta=0.386 and beta=0.297, p<0.001); avoidance, social support and watching TV contributed to passive attitude (beta=0.301, beta=0.243 and beta=0.212, p<0.001). As per the relationship between latent factors and their influence on depression, disability contributed to passive attitude (beta=0.855, p<0.001) while both passive and active attitude significantly influenced depression (beta=0.729 and beta=-0.456, p<0.001).CONCLUSION: as practical implication of our model, favoring exercise would enhance active attitude and its positive impact on mental well-being while, at the same time, reducing the negative impact of disability on depression, representing a valuable tool to face COVID-19 related mental distress

COVID-19 pandemic and mental distress in Multiple Sclerosis: implications for clinical management

in multiple sclerosis (MS), disease-related factors and dysfunctional coping might favour the development of mental distress induced by COVID-19 containment measures