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 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

Lesion-to-ventricle distance and other risk factors for the persistence of newly formed black holes in relapsing–remitting multiple sclerosis

2013 ◽  
Vol 20 (3) ◽  
pp. 322-330 ◽  
Author(s):  
Athina Papadopoulou ◽  
Milena Menegola ◽  
Jens Kuhle ◽  
Sreeram V Ramagopalan ◽  
Marcus D’Souza ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Holes ◽  
Subventricular Zone ◽  
Magnetic Resonance Images ◽  
Lateral Ventricles ◽  
Relapsing Remitting ◽  
Specific Factors ◽  
One Year ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Relationship

Background: Progenitor cells from the subventricular zone (SVZ) of the lateral ventricles are assumed to contribute to remyelination and resolution of black holes (BHs) in multiple sclerosis (MS). This process may depend on the distance between the lesion and the SVZ. Objective: The objective of this paper is to investigate the relationship between lesion-to-ventricle (LV) distance and persistence of new BHs. Methods: We analysed the magnetic resonance images (MRIs) of 289 relapsing–remitting (RR) MS patients, obtained during a multi-centre, placebo-controlled phase II trial over one year. Results: Overall, 112/289 patients showed 367 new BHs at the beginning of the trial. Of these, 225 were located in 94/112 patients at the level of the lateral ventricles on axial MRIs and included in this analysis. In total, 86/225 (38%) BHs persisted at month 12. LV distance in persistent BHs (PBHs) was not longer than in transient BHs. In fact PBHs tended to be closer to the SVZ than transient BHs. A generalised linear mixed multivariate model adjusted for BHs clustered within a patient and including patient- as well as lesion-specific factors revealed size, ring contrast enhancement, and shorter LV distance as independent predictors for BH persistence. Conclusion: Location of BHs close to the lateral ventricles does not appear to favourably influence the resolution of new BHs in RRMS.

scholarly journals Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis

2013 ◽  
Vol 20 (8) ◽  
pp. 1066-1073 ◽  
Author(s):  
Silvia Mangia ◽  
Adam F Carpenter ◽  
Andy E Tyan ◽  
Lynn E Eberly ◽  
Michael Garwood ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Magnetic Resonance Images ◽  
Relaxation Methods ◽  
Normal Appearing White Matter ◽  
Relaxation Parameters ◽  
Relapsing Remitting ◽  
Cortical Gray Matter ◽  
The Brain

Background: Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that is “normal appearing” on T1-weighted and T2-weighted magnetic resonance images. Objectives: With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods: Nine relapsing–remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to the AC-PC line. Results: The MT ratio of regions encompassing the normal-appearing white matter (NAWM) was different in MS patients as compared with controls ( p = 0.043); however, the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups ( p = 0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p = 0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical gray matter for any relaxation parameter. Conclusions: The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

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.

The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study

2007 ◽  
Vol 13 (4) ◽  
pp. 517-526 ◽  
Author(s):  
R.K. Zabad ◽  
L.M. Metz ◽  
T.R. Todoruk ◽  
Y. Zhang ◽  
J.R. Mitchell ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Baseline Period ◽  
Open Label ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Immune Changes ◽  
Cell Adhesion Molecule 1 ◽  
The Impact ◽  
Metalloproteinase 9

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS. Multiple Sclerosis 2007; 13: 517-526. http://msj.sagepub.com

scholarly journals MATRIX METALLOPROTEINASE-9 AND INFLAMMATION IN DIFFERENT TYPES OF MULTIPLE SCLEROSIS

2016 ◽  
Vol 1 ◽  
pp. 39-44
Author(s):  
Nataliya Voloshyna ◽  
Vitaliy Vasylovskyy ◽  
Tatyana Nehreba ◽  
Maksym Chernenko ◽  
Viktoriya Vovk
Keyword(s):  
Multiple Sclerosis ◽  
Matrix Metalloproteinase ◽  
Inflammatory Process ◽  
Progressive Multiple Sclerosis ◽  
Pathological Process ◽  
Matrix Metalloproteinase 9 ◽  
Primary Progressive Multiple Sclerosis ◽  
Central Nervous System Damage ◽  
Relapsing Remitting ◽  
Metalloproteinase 9

Different clinical courses of multiple sclerosis, heterogeneity of its clinical implications, different effect of immunomodulatory therapy for the same clinical forms implies various pathogenetic mechanisms of central nervous system damage at this disease. Applicability of immunological and biochemical markers for the estimation of immunocorrecting and anti-inflammatory therapy efficacy is important. This research aims at improvement of pathological process stages diagnostics at multiple sclerosis and further therapy optimization depending on the activity of the inflammatory process. In the article matrix metalloproteinase-9 rate was assessed in 135 patients with multiple sclerosis of different course types and at different activity stages of the pathological process. The highest matrix metalloproteinase-9 rates were in patients with relapsing-remitting type at the stage of exacerbation, with the lowest rate being in patients with primary-progressive multiple sclerosis. Determination of matrix metalloproteinase-9 rate allows to assess the degree of inflammatory process expression and to monitor the efficacy of multiple sclerosis treatment.

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.

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