scholarly journals Cutting Edge: Mast Cells Regulate Disease Severity in a Relapsing–Remitting Model of Multiple Sclerosis

2011 ◽  
Vol 186 (6) ◽  
pp. 3294-3298 ◽  
Author(s):  
Blayne A. Sayed ◽  
Margaret E. Walker ◽  
Melissa A. Brown
Keyword(s):  
Multiple Sclerosis ◽  
Mast Cells ◽  
Disease Severity ◽  
Cutting Edge ◽  
Relapsing Remitting

scholarly journals Usability of a Mobile App for Real-Time Assessment of Fatigue and Related Symptoms in Patients With Multiple Sclerosis: Observational Study

10.2196/19564 ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. e19564
Author(s):  
Miklos Palotai ◽  
Max Wallack ◽  
Gergo Kujbus ◽  
Adam Dalnoki ◽  
Charles Guttmann
Keyword(s):  
Multiple Sclerosis ◽  
Real Time ◽  
Disease Severity ◽  
Temporal Dynamics ◽  
Mobile App ◽  
Sleep Habits ◽  
Symptom Monitoring ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Time Assessment

Background Although fatigue is one of the most debilitating symptoms in patients with multiple sclerosis (MS), its pathogenesis is not well understood. Neurogenic, inflammatory, endocrine, and metabolic mechanisms have been proposed. Taking into account the temporal dynamics and comorbid mood symptoms of fatigue may help differentiate fatigue phenotypes. These phenotypes may reflect different pathogeneses and may respond to different mechanism-specific treatments. Although several tools have been developed to assess various symptoms (including fatigue), monitor clinical status, or improve the perceived level of fatigue in patients with MS, options for a detailed, real-time assessment of MS-related fatigue and relevant comorbidities are still limited. Objective This study aims to present a novel mobile app specifically designed to differentiate fatigue phenotypes using circadian symptom monitoring and state-of-the-art characterization of MS-related fatigue and its related symptoms. We also aim to report the first findings regarding patient compliance and the relationship between compliance and patient characteristics, including MS disease severity. Methods After developing the app, we used it in a prospective study designed to investigate the brain magnetic resonance imaging correlates of MS-related fatigue. In total, 64 patients with MS were recruited into this study and asked to use the app over a 2-week period. The app features the following modules: Visual Analogue Scales (VASs) to assess circadian changes in fatigue, depression, anxiety, and pain; daily sleep diaries (SLDs) to assess sleep habits and quality; and 10 one-time questionnaires to assess fatigue, depression, anxiety, sleepiness, physical activity, and motivation, as well as several other one-time questionnaires that were created to assess those relevant aspects of fatigue that were not captured by existing fatigue questionnaires. The app prompts subjects to assess their symptoms multiple times a day and enables real-time symptom monitoring through a web-accessible portal. Results Of 64 patients, 56 (88%) used the app, of which 51 (91%) completed all one-time questionnaires and 47 (84%) completed all one-time questionnaires, VASs, and SLDs. Patients reported no issues with the usage of the app, and there were no technical issues with our web-based data collection system. The relapsing-remitting MS to secondary-progressive MS ratio was significantly higher in patients who completed all one-time questionnaires, VASs, and SLDs than in those who completed all one-time questionnaires but not all VASs and SLDs (P=.01). No other significant differences in demographics, fatigue, or disease severity were observed between the degrees of compliance. Conclusions The app can be used with reasonable compliance across patients with relapsing-remitting and secondary-progressive MS irrespective of demographics, fatigue, or disease severity.

The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis

2010 ◽  
Vol 17 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Silvia Rossi ◽  
Fabio Buttari ◽  
Valeria Studer ◽  
Caterina Motta ◽  
Paolo Gravina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Disease Severity ◽  
Receptor Gene ◽  
Severe Disease ◽  
Autoimmune Encephalomyelitis ◽  
Homozygous Genotype ◽  
Relapsing Remitting ◽  
Risk Of Progression ◽  
Cnr1 Gene

Background: Genetic and pharmacological inactivation of cannabinoid CB1 receptors (CB1Rs) exacerbates disease course in experimental autoimmune encephalomyelitis, suggesting that CB1Rs might play a role in the neurodegenerative damage associated with multiple sclerosis (MS). Objectives: To see whether CNR1 gene polymorphism could influence disease progression in relapsing–remitting MS. Methods: The genotype of 350 patients for the number of AAT repeats was characterized and correlation studies were performed with measures of disease severity and progression. Results: MS patients with the homozygous genotype for long AAT repeats in the CNR1 gene had more severe disease and higher risk of progression. These subjects had significantly higher scores on both the progression index and the MS severity scale. Furthermore, the percentage of patients with MS functional composite score progression or Bayesian Risk Estimate for MS (BREMS) score ≥2 (considered at very high risk of secondary progression) was significantly higher in the AAT long group than in the short group, while the frequency of patients with BREMS score ≤−0.63 (very likely to remain progression-free) was not significantly different between the two groups, although lower in the long group. Finally, the frequency of patients prescribed a second-line treatment was significantly higher among subjects of the AAT long group, providing a further, indirect indication of higher disease severity. Conclusions: The results of the present investigation point to CB1R as an important modulator of disease severity in relapsing MS subjects.

Ring-enhancement in multiple sclerosis: marker of disease severity

2001 ◽  
Vol 7 (3) ◽  
pp. 167-167 ◽  
Author(s):  
K Morgen ◽  
N O Jeffries ◽  
R Stone ◽  
R Martin ◽  
N D Richert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Severity ◽  
Multiple Logistic Regression Analysis ◽  
Baseline Period ◽  
Pathological Process ◽  
Magnetic Resonance Images ◽  
Conventional Mri ◽  
Potential Association ◽  
Relapsing Remitting ◽  
Duration Of Disease

Correlations between conventional MRI measures of disease activity and clinical disability in multiple sclerosis (MS) have been disappointing. Because ring-enhancing lesions may reflect a more destructive pathology, we tested their potential association with disease severity. We evaluated active lesions with regard to their enhancement pattern on serial magnetic resonance images in a cohort of 28 patients with relapsing-remitting MS. The percentage of ring-enhancing lesions correlated with EDSS, T2 lesion load and duration of disease and predicted the occurrence of relapses during the baseline period of observation as well as after 3 years of follow-up in multiple logistic regression analysis. The findings suggest that the pathological process reflected by ring-enhancing lesions may contribute to more severe clinical disease.

scholarly journals CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis

2020 ◽  
Vol 11 ◽  
pp. 204062232094737
Author(s):  
Jeroen FJ Bogie ◽  
Elien Grajchen ◽  
Elien Wouters ◽  
Bieke Broux ◽  
Piet Stinissen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Severity ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Autoimmune Encephalomyelitis ◽  
Cell Compartments ◽  
Humanized Monoclonal Antibody ◽  
Relapsing Remitting ◽  
Eae Model ◽  
Cns Delivery

Background and aims: Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing–remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model. Methods: Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters. Results: We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice. Conclusion: Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS.

Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition

2010 ◽  
Vol 17 (3) ◽  
pp. 344-352 ◽  
Author(s):  
Anneke Van der Walt ◽  
J Stankovich ◽  
M Bahlo ◽  
BV Taylor ◽  
IAF Van der Mei ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Severity ◽  
Brain Atrophy ◽  
Age Of Onset ◽  
Allelic Variation ◽  
Cerebral Atrophy ◽  
Population Based ◽  
Clinical Disease ◽  
Multiple Sclerosis Disease ◽  
Relapsing Remitting

Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.

scholarly journals Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1β and IL-1ra production in multiple sclerosis

2003 ◽  
Vol 12 (2) ◽  
pp. 89-94 ◽  
Author(s):  
Hans M. Schrijver ◽  
Jaco van As ◽  
J. Bart A. Crusius ◽  
Christien D. Dijkstra ◽  
Bernard M. J. Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Disease Severity ◽  
Autoimmune Disorder ◽  
Dose Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Course ◽  
Specific Combination ◽  
Relapsing Remitting ◽  
Genes Encoding

Background:Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1Band IL-1 receptor antagonist(IL−1RN)genes (i.e.IL−1RNallele2+/IL−1B+3959allele 2−) with disease severity in MS. Extending this observation, we investigated whether IL-1β and IL-1ra production differed depending on carriership of this gene combination.Methods:Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood,in vitroIL-1β and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide.Results:Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous forIL−1RNallele 2. In patients, Il-1ra production was higher and IL-1β production lower compared with controls. In primary progressive patients, the IL-1β /IL-1ra ratio was significantly lower than in relapsing-remitting patients.Conclusion:Our results suggest higher in vitro IL-1ra production in carriers ofIL−1RNallele 2, with an indication of an allelic dose-effect relationship.

scholarly journals IL-15 Is Overexpressed in γδ T Cells and Correlates with Disease Severity in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Vol 10 (18) ◽  
pp. 4174
Author(s):  
Michał K. Zarobkiewicz ◽  
Wioleta Kowalska ◽  
Izabela Morawska ◽  
Paweł Halczuk ◽  
Konrad Rejdak ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Disease Severity ◽  
Γδ T Cells ◽  
Functional Studies ◽  
Multiple Sclerosis Pathogenesis ◽  
Distinct Subset ◽  
Relapsing Remitting ◽  
Interleukin 15 ◽  
Relapsing Remitting Multiple Sclerosis

Interleukin 15 (IL-15) is known to be involved in the pathogenesis of multiple sclerosis (MS). An animal study revealed a distinct subset of IL-15-producing γδ T cells that correlate with disease severity. The aim of the current study was to test whether such a subset is also present in humans and its importance for the pathogenesis of MS. The peripheral blood from 29 patients with relapsing-remitting MS (including 6 relapses) and 22 controls was stained with monoclonal antibodies and analyzed with flow cytometry. The existence of IL-15+ γδ T cells was confirmed. Moreover, the percentage of IL-15+ γδ T is significantly increased in MS patients and correlates with disease severity. Nevertheless, additional functional studies are needed to fully understand the importance of those cells in multiple sclerosis pathogenesis

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