Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the ...relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients.
We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration <5 years), 29 with late RRMS (disease duration ≥ 5 years) and 20 with secondary-progressive MS (SPMS). The distribution and evolution of regional cortical thickness and GM lesions were assessed during 5-year follow-up.
The results showed that new lesions appeared more frequently in hippocampus and parahippocampal gyri (9.1%), insula (8.9%), cingulate cortex (8.3%), superior frontal gyrus (8.1%), and cerebellum (6.5%). The aforementioned regions showed the greatest reduction in thickness/volume, although (several) differences were observed across subgroups. The correlation between the appearance of new cortical lesions and cortical thinning was stronger in CIS (r2 = 50.0, p<0.001) and in early RRMS (r2 = 52.3, p<0.001), compared to late RRMS (r2 = 25.5, p<0.001) and SPMS (r2 = 6.3, p = 0.133).
We conclude that GM atrophy and lesions appear to be different signatures of cortical disease in MS having in common overlapping spatio-temporal distribution patterns. However, the correlation between focal and diffuse damage is only moderate and more evident in the early phase of the disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) is generally diagnosed at an early age, making the acceptance of this chronic disease challenging. Research dedicated to young adults with MS (YawMS) is still limited. A ...biopsychosocial co-created intervention for YawMS integrating social, physical and psychological activities was developed (ESPRIMO intervention) in order to improve the quality of life (QoL) and well-being. This pre-post intervention assessment study examines the feasibility of the ESPRIMO intervention and its signal of efficacy.
Inclusion criteria were: age 18-45 years, MS diagnosis, Expanded Disability Status Scale score < 3.5. After giving informed consent, YawMS completed a battery of questionnaires, which was repeated after the intervention. The battery included a bespoke feasibility scale, the COOP/WONCA charts, and the Short Form-12 Health Survey (SF-12).
Fifty-three YAwMS were enrolled and 43 (81.1%) completed the intervention. The majority of the sample positively rated the pleasantness, usefulness and feasibility of the intervention. A significant change in the COOP/WONCA "general QoL" chart (
= 3.65;
< 0.01) and SF-12 mental wellbeing component (
= -3.17;
< 0.01) was found.
ESPRIMO is an innovative intervention that is feasible; preliminary results show an improvement in QoL and mental wellbeing. Further studies are needed to test its efficacy and evaluate future implementation in health services.
: ClinicalTrials.gov, NCT04431323.
Background:
Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ...ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax.
Objectives:
The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ).
Methods:
Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use.
Results:
Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed.
Conclusion:
Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.
Recent evidence has demonstrated that the COVID-19 pandemic is taking a toll on the mental health of the general population. The psychological consequences might be even more severe for patients with ...special healthcare needs and psychological vulnerabilities due to chronic diseases, such as multiple sclerosis (MS). Thus, we aimed to explore the psychological impact of this pandemic and of the subsequent healthcare service changes on young adults with MS living in Italy and to examine their coping strategies and preferences regarding psychological support in the aftermath of the pandemic.
Data were collected using a cross-sectional, web-based survey advertised on social networks. We report both quantitative (descriptive statistics,
-tests, and one-way ANOVA) and qualitative data (inductive content analysis).
Two hundred and forty-seven respondents (mean age 32 ± 7 years), mainly with relapsing-remitting MS, from all Italian regions participated. Participants felt more worried, confused, sad, and vulnerable because of the disease "during" the pandemic in comparison to their self-evaluation of the period "before" the COVID-19 outbreak. Similarly, their perception of control over MS decreased "during" the pandemic in comparison to the retrospective evaluation of the period "before" the COVID-19 outbreak (
< 0.01). Canceled/postponed visits/exams were listed as the most frequent MS management changes, with modified/postponed pharmacological treatment representing the most stressful change. Psychological support in dealing with pandemic-related fears and improving MS acceptance and well-being was considered extremely important by almost 40% of the respondents. Different coping strategies were mentioned in the qualitative section of the survey, with social support, hobbies, and keeping busy being the most frequent ones.
Considering the enormous impact of the pandemic on young adults with MS, we urge MS clinical centers to implement psychological support programs that address the potentially long-lasting psychological negative impact, thus fostering the therapeutic alliance that is being threatened by the infection prevention measures imposed during the pandemic, and promoting psychological resources for adaptively managing future waves of COVID-19.
Multiple sclerosis (MS), the most common neurological disease that causes disability in youth, does not only affect physical functions but is also associated with cognitive impairment, fatigue, ...depression, and anxiety and can significantly impact health-related quality of life (HRQoL). Since MS is generally diagnosed at a young age-a period of great significance for personal, relational, and professional development-adaptation can become highly challenging. Therefore, enhancing the competence of young people to adaptively cope with these potential challenges is of utmost importance in order to promote their potentialities and talents. It has been shown that psychological interventions targeting MS patients can enhance resilience and HRQoL and that regular physical activity (PA) and social engagement can improve psychological well-being. However, literature on the development of global interventions based on the bio-psycho-social model of the disease is missing. Even less attention has been paid to interventions dedicated to young adults with MS (YawMS) and to the involvement of patients in the development of such programs.
In collaboration with MS patients, this study aims to develop a bio-psycho-social intervention (ESPRIMO) for YawMS, aiming to improve their HRQoL and to explore its feasibility, acceptability, and effects.
To tailor the intervention to the specific needs of YawMS, "patient engagement principles" will be adopted in the co-creation phase, performing a web survey and focus groups with patients and healthcare professionals. In the intervention phase, a pilot sample of 60 young adults with MS will be enrolled. The co-created intervention, composed of group sessions over a 12-week period, will cover psycho-social strategies and include physical activities. Adopting a longitudinal, pre-post evaluation design, self-report questionnaires measuring HRQoL and other bio-psycho-social features (e.g., resilience, well-being, mindfulness traits, self-efficacy, perceived social support, psychological symptoms, illness perception, committed action, fatigue, attitudes, subjective norms, perceived behavioral control, motivation, perception of autonomy support for PA, barriers and intentions to PA) will be administered, the quantity and quality of PA will be measured, and a questionnaire developed by the authors will be used to evaluate the feasibility and acceptability of the ESPRIMO intervention.
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<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001) were predictive of treatment discontinuation.
These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neurofilaments are the major structural proteins of the neuronal cytoskeleton and are classified according to molecular weight into heavy, intermediate, and light chains. They are released into the ...interstitial fluid and cerebrospinal fluid (CSF) as a consequence of axonal damage. In particular, the light chain (NfL) represents the most abundant and soluble subunit and has been demonstrated to be increased in the CSF of patients with inflammatory, degenerative, vascular, or traumatic injuries in correlation with clinical and radiological activity. Similar results have been obtained measuring serum NfL with high-sensitivity single-molecule array, which enables reliable and repeatable measurement of the low NfL concentrations in serum. In particular, CSF and serum NfL values are strongly correlated in patients with multiple sclerosis (MS) and have been demonstrated to be increased in patients with MS and clinically isolated syndromes (CIS) in accordance with clinical and radiological activity. NfL levels increase in patients with a recent relapse and seem to predict cognitive impairment, long-term outcome, and conversion of CIS to MS. The few available data on patients with other demyelinating diseases suggest that NfL levels are also increased in neuromyelitis optica spectrum disorders and related conditions in correlation with attack severity, suggesting that axonal damage may occur in these disorders. We herein report and discuss published data on the role of NfL as a possible predictor of disease activity, clinical outcome and treatment response in patients with demyelinating conditions of the central nervous system.
•NfL levels are increased in patients with MOGAD at onset•NfL levels decrease over time in most patients with MOGAD•NfL levels do not increase significantly during relapses in patients with ...MOGAD•Axonal damage predominantly occurs at onset in patients with MOGAD
The unpredictable course and uncertain impact of relapses make treatment strategies of anti-myelin oligodendrocyte glycoprotein antibodies associated disorders (MOGAD) challenging. We analysed neurofilament light chain levels (NfL) in onset and follow-up sera of 18 patients with MOGAD to clarify the timing of axonal damage. In comparison with disease onset values (median 8.9 pg/mL, range 1.8-97), NfL levels remained stable or decreased in most follow-up measurements (n=52, median 6.7 pg/mL, range 0.2-207), including those measured on relapses. The predominant axonal damage occurs during onset, which could be the main driving factor of final disability, with subsequent relevant clinical and therapeutic implications.
Background
Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological ...mechanisms compared to multiple sclerosis.
Objective
The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis.
Methods
Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays. First, we analysed a panel of 32 cytokines/chemokines in a discovery group (nine aquaporin-4-antibody seropositive, nine myelin oligodendrocyte glycoprotein-antibody seropositive, eight encephalitis, 10 multiple sclerosis). Significantly dysregulated cytokines/chemokines were validated in a second cohort (11 aquaporin-4-antibody seropositive, 18 myelin oligodendrocyte glycoprotein-antibody seropositive, 18 encephalitis, 33 multiple sclerosis).
Results
We found 11 significantly altered cytokines/chemokines in cerebrospinal fluid and serum samples in the discovery group (a proliferation-inducing ligand, fractalkine=CX3CL1, growth-regulated oncogene-α, interleukin-1 receptor antagonist, interleukin-6, interleukin-8=CXCL8, interleukin-10, interleukin-21, interferon-ɣ-induced protein-10=CXCL10, monokine induced by interferon-ɣ=CXCL9, macrophage inflammatory protein-1ß=CCL4). Most of these cytokines/chemokines were up-regulated in autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein positive patients compared to multiple sclerosis. We confirmed these results for cerebrospinal fluid interleukin-6 and serum interleukin-8, growth-regulated oncogene-α, a proliferation-inducing ligand and macrophage inflammatory protein-1β in the validation set. Receiver-operating characteristic analysis revealed increased levels of cerebrospinal fluid interleukin-6, serum interleukin-8 and growth-regulated oncogene-α in most patients with autoantibody-associated neurological diseases.
Conclusion
This study suggests that distinctive cerebrospinal fluid and serum cytokine/chemokine profiles are associated with autoantibody-mediated demyelination, but not with multiple sclerosis.
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