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.
Background:
Optical coherence tomography (OCT) angiography is a new method to assess the density of the vascular networks. Vascular abnormalities are considered involved in multiple sclerosis (MS) ...pathology.
Objective:
To assess the presence of vascular abnormalities in MS and to evaluate their correlation to disease features.
Methods:
A total of 50 MS patients with and without history of optic neuritis (ON) and 46 healthy subjects were included. All underwent spectral domain (SD)-OCT and OCT angiography. Clinical history, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS) and disease duration were collected.
Results:
Angio-OCT showed a vessel density reduction in eyes of MS patients when compared to controls. A statistically significant reduction in all SD-OCT and OCT angiography parameters was noticed both in eyes with and without ON when compared with control eyes. We found an inverse correlation between SD-OCT parameters and MSSS (p = 0.003) and between vessel density parameters and EDSS (p = 0.007).
Conclusion:
We report a vessel density reduction in retina of MS patients. We highlight the clinical correlation between vessel density and EDSS, suggesting that angio-OCT could be a good marker of disease and of disability in MS.
Background
As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, a large amount of consultations will be delivered through tele-medicine, especially for diseases causing chronic ...disability and requiring immunomodulatory treatments, such as multiple sclerosis (MS).
Methods
We have hereby reviewed available tools for tele-neurology examination in MS, including components of neurological examination that can be assessed through video, patient-reported outcome measures (PROMs), and digital technology.
Results
Overall, we have suggested a battery for assessing MS disability and relapses on tele-medicine, which brings together conventional examination, PROMs (e.g., Patient Determined Disease Steps, MS Impact Scale), and cognitive tests (Symbol Digit Modalities Test) that can be delivered remotely and in multiple languages.
Discussion
The use of common tools for neurological examination could improve tele-neurology practice for both general neurologists and MS specialists, and quality of care for people with MS.
e-Health and multiple sclerosis: An update Lavorgna, Luigi; Brigo, Francesco; Moccia, Marcello ...
Multiple Sclerosis Journal,
11/2018, Letnik:
24, Številka:
13
Book Review, Journal Article
Recenzirano
Odprti dostop
e-Health (or digital healthcare) is becoming increasingly relevant in multiple sclerosis (MS) clinical management. We aim to review and discuss current status and future perspective of e-health in ...people with multiple sclerosis (pwMS). The first part of this review describes how information on MS can be conveyed through the Web and digital media. The second part illustrates recent advances in digital technology that can improve clinical management and in motor and cognitive rehabilitation of pwMS. Finally, this review advocates future development of the “digital case manager” as a new figure to coordinate clinical management and care of pwMS. The digital revolution is changing the medical approach to MS in terms of information conveying and sharing, rehabilitation, and healthcare management.
Human CD4+CD25hiFOXP3+ regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg ...cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impaired in subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorder associated with reduced Treg cell proliferative capacity. Treatment of RRMS subjects with dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as major target for the rescue of Treg cell proliferation.
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•SLC7A11 controls Treg cell proliferation induced by signals of pseudo-starvation•SLC7A11 coordinates the antioxidant response in proliferating Treg cells•Growth-defective Treg cells from RRMS patients fail to induce SLC7A11•DMF therapy restores Treg cell proliferation, inducing SLC7A11 in RRMS patients
Altered immunological self-tolerance in relapsing-remitting multiple sclerosis (RRMS) associates with a reduced regulatory T cell proliferation. Procaccini et al. show a key role for the amino acid transporter SLC7A11 in this process, as its induction is impaired in RRMS patients and can be restored by treatment with dimethyl fumarate.
Background:
Emergency hospital admissions are common in multiple sclerosis (MS), and can highlight unmet medical needs.
Objectives:
To evaluate burden, predictors and outcomes of MS emergency ...admissions.
Methods:
This is a population-based study, conducted in the Campania Region (South Italy) from 2015 to 2019, using hospital discharge records, drug prescriptions and outpatients. The risk of emergency hospital admissions and the likelihood of worse outcomes were evaluated using the Cox regression and multinomial logistic regression models, respectively, in relation to age, sex, disease-modifying treatments (DMTs), comorbidities and adherence.
Results:
We recorded 1225 emergency admissions for 1001 patients (out of 5765 prevalent MS patients), overall costing 4,143,764.67 EUR. The risk of emergency admissions increased with age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) = 1.01, 1.03; p < 0.01) and comorbidities (HR = 1.62; p < 0.01), and decreased in patients using DMTs (interferon beta/peg-interferon beta/glatiramer acetate HR = 0.19; p < 0.01; teriflunomide/dimethyl-fumarate/fingolimod HR = 0.18; p < 0.01, and alemtuzumab/cladribine/natalizumab/ocrelizumab HR = 0.21; p < 0.01), and with higher adherence (HR = 0.18; 95% CI = 0.13, 0.26; p < 0.01). Following emergency admission, older age was associated with probability of death (n = 63) (odds ratio (OR) = 1.06; p < 0.01) and discharge to long-term facility (n = 65) (OR = 1.03; p = 0.01).
Conclusion:
With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.
Background:
Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines.
Objective:
In this study we aimed to monitor the ...risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs).
Methods:
Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT.
Results:
19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75–4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02).
Conclusions:
The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.
Background We aim to overcome limitations of previous clinical and population-based studies by merging a clinical registry to routinely-collected healthcare data, and to specifically describe ...differences in clinical outcomes, healthcare resource utilization and costs between interferon beta formulations for multiple sclerosis (MS). Methods We included 850 patients with MS treated with interferon beta formulations, from 2015 to 2019, seen at the MS Clinical Care and Research Centre (Federico II University of Naples, Italy) and with linkage to routinely-collected healthcare data (prescription data, hospital admissions, outpatient services). We extracted and computed clinical outcomes (relapses, 6-month EDSS progression using a roving EDSS as reference), persistence (time spent on a specific interferon beta formulation), adherence (medication possession ratio (MPR)), healthcare resource utilization and costs (annualized hospitalization rate (AHR), costs for hospital admissions and DMTs). To evaluate differences between interferon beta formulations, we used linear regression (adherence), Poisson regression (AHR), mixed-effect regression (costs), and Cox-regression models (time varying variables); covariates were age, sex, treatment duration, baseline EDSS and adherence. Results Looking at clinical outcomes, rates of relapses and EDSS progression were lower than studies run on previous cohorts; there was no differences in relapse risk between interferon beta formulations. Risk of discontinuation was higher for Betaferon®/Extavia® (HR = 3.28; 95%CI = 2.11, 5.12; p<0.01). Adherence was lower for Betaferon®/Extavia® (Coeff = -0.05; 95%CI = -0.10, -0.01; p = 0.02), and Avonex® (Coeff = -0.06; 95%CI = -0.11, -0.02; p<0.01), when compared with Rebif® and Plegridy® (Coeff = 0.08; 95%CI = 0.01, 0.16; p = 0.02). AHR and costs for MS hospital admissions were higher for Betaferon®/Extavia® (IRR = 2.38; 95%CI = 1.01, 5.55; p = 0.04; Coeff = 14.95; 95%CI = 1.39, 28.51; p = 0.03). Conclusions We have showed the feasibility of merging routinely-collected healthcare data to a clinical registry for future MS research, and have confirmed interferon beta formulations play an important role in the management of MS, with positive clinical outcomes. Differences between interferon beta formulations are mostly driven by adherence and healthcare resource utilization.
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