scholarly journals GANAB as a Novel Biomarker in Multiple Sclerosis: Correlation with Neuroinflammation and IFI35

2021 ◽  
Vol 14 (11) ◽  
pp. 1195
Author(s):  
Roberto De Masi ◽  
Stefania Orlando
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Disease Duration ◽  
Treated Group ◽  
Lesion Load ◽  
Mean Values ◽  
Glucosidase Ii ◽  
Ifn Therapy ◽  
A Prospective Study

Multiple sclerosis (MS) still lacks reliable biomarkers of neuroinflammation predictive for disease activity and treatment response. Thus, in a prospective study we assessed 55 MS patients (28 interferon (IFN)-treated, 10 treated with no-IFN therapies, 17 untreated) and 20 matched healthy controls (HCs) for the putative correlation of the densitometric expression of glucosidase II alpha subunit (GANAB) with clinical/paraclinical parameters and with interferon-induced protein 35 (IFI35). We also assessed the disease progression in terms of the Rio Score (RS) in order to distinguish the responder patients to IFN therapy (RS = 0) from the non-responder ones (RS ≥ 1). We found GANAB to be 2.51-fold downregulated in the IFN-treated group with respect to the untreated one (p < 0.0001) and 3.39-fold downregulated in responder patients compared to the non-responders (p < 0.0001). GANAB correlated directly with RS (r = 0.8088, p < 0.0001) and lesion load (LL) (r = 0.5824, p = 0.0014) in the IFN-treated group and inversely with disease duration (DD) (r = −0.6081, p = 0.0096) in the untreated one. Lower mean values were expressed for GANAB than IFI35 in IFN responder (p < 0.0001) and higher mean values in the non-responder patients (p = 0.0022). Inverse correlations were also expressed with IFI35 in the overall patient population (r = −0.6468, p < 0.0001). In conclusion, the modular expression of GANAB reflects IFI35, RS, DD, and LL values, making it a biomarker of neuroinflammation that is predictive for disease activity and treatment response in MS.

scholarly journals AB0101 THE IMPACT OF TIME SPAN TO ACHIEVE BOOLEAN REMISSION FOR MAINTAINING DISEASE ACTIVITY AFTER ACQUISITION IN RHEUMATOID ARTHRITIS PATIENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1079.1-1079
Author(s):  
I. Yoshii
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Remission Rate ◽  
Mean Value ◽  
Time Span ◽  
Mean Values ◽  
The Mean ◽  
The Relationship

Background:Boolean remission criteria is one most popular and stringent criteria in treating patient with rheumatoid arthritis (RA), because it may guarantees a stable clinical course after attaining remission.Objectives:Impact of time span from initiation to achieving Boolean remission on maintaining disease activity, daily activities, and quality of life after attaining Boolean remission was investigated from daily clinical practice data.Methods:685 patients with RA since August 2010 under the T2T strategy were treated. They were monitored for their TJC, SJC, PGA, EGA, CRP, and disease activity indices such as CDAI, SDAI, DAS28, and Boolean criteria at every visit. HAQ-DI score, pain score using visual analog scale (PS-VAS), and EQ-5D were also monitored, and the quality of life score (QOLS) calculated from EQ-5D was determined at every visit from the time of diagnosis (baseline).Of 685 patients, 465 patients had achieved Boolean remission >1 times, and were consecutively followed up for >3 years. These patients were enrolled in the study. Time span from the first visit to first Boolean remission was calculated. The relationship between the time span and each of background parameters, and the relationship between the time span and each of the mean values of the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at the first Boolean remission and thereafter was evaluated statistically.Patients were subsequently divided into the G ≤ 6 and G > 6 groups based on the achievement of first Boolean remission within two groups: time span G ≤ 6 months and G > 6 months. The two groups were compared with regard to the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at first visit and at the time of first Boolean remission, and the mean values of these parameters after remission were evaluated statistically. Moreover, changes of these parameters and the mean Boolean remission rate after the first remission, and SDAI remission rate at the first Boolean remission to thereafter were compared between the two groups statistically.Results:Out of 465 patients, females comprised 343 (73.7%), and the mean age was 67.8 years (range, from 21–95 years). The mean disease duration at first visit was 6.1 years (range, from 1 months–45 years). The mean follow up length was 88.1 months (range: 36–122 months; median: 85 months) and mean time span from the first visit to the first Boolean remission was 8.1 months. The mean SDAI score, HAQ score, PS-VAS, and the QOLS at first visit were 13.3, 0.467, 33.2, and 0.834, respectively. Among the study parameters, PS-VAS and QOLS were significantly correlated with the time span. For parameters at the first Boolean remission, HAQ-DI score, PS-VAS, and QOLS demonstrated significant correlation with the time span, whereas SDAI, HAQ-DI score, PS-VAS, SHS, and QOLS after the Boolean remission demonstrated significant correlation with the time span.The comparison between the G ≤ 6 and the G > 6 groups revealed that the disease duration, HAQ score, and PS-VAS at baseline in the G > 6 were significantly higher than that in the G ≤ 6 group, and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group at baseline. Similarly, the HAQ score and PS-VAS at the first Boolean remission in the G > 6 group were significantly higher than that in the G ≤ 6 group, whereas QOLS in the G ≤ 6 group demonstrated no significant difference compared with that in the G > 6 group.The mean value of the SDAI score after the first Boolean remission in the G > 6 group was significantly higher than that in the G ≤ 6 group. Similarly, the SDAI score, HAQ score, and PS-VAS after the first Boolean remission in the G > 6 group were also significantly higher than those in the G ≤ 6 group, and the mean value of the QOLS in the G ≤ 6 group were significantly higher than that in the G > 6 group. The Boolean remission rate and SDAI remission rate after the first Boolean remission were significantly higher in the G ≤ 6 group than those in the G > 6 group.Conclusion:Attaining Boolean remission ≤ 6 months for RA has significant benefit for more stable disease control, that leads good maintenance of ADL.Disclosure of Interests:None declared

Serum levels of leptin and adiponectin are not associated with disease activity or treatment response in multiple sclerosis

2018 ◽  
Vol 323 ◽  
pp. 73-77 ◽  
Author(s):  
Silje Stokke Kvistad ◽  
Kjell-Morten Myhr ◽  
Trygve Holmøy ◽  
Jūratė Šaltytė Benth ◽  
Stig Wergeland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Serum Levels

Microstructural fronto-striatal and temporo-insular alterations are associated with fatigue in patients with multiple sclerosis independent of white matter lesion load and depression

2019 ◽  
Vol 26 (13) ◽  
pp. 1708-1718 ◽  
Author(s):  
Miklos Palotai ◽  
Michele Cavallari ◽  
Ismail Koubiyr ◽  
Alfredo Morales Pinzon ◽  
Aria Nazeri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Physical Disability ◽  
Disease Duration ◽  
White Matter Lesion ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Regions ◽  
Specific Substrate ◽  
Patient Stratification ◽  
Lesion Load

Background: Fatigue in multiple sclerosis (MS) has been inconsistently associated with disruption of specific brain circuitries. Temporal fluctuations of fatigue have not been considered. Objective: The aim of this study was to investigate the association of fatigue with brain diffusion abnormalities, using robust criteria for patient stratification based on longitudinal patterns of fatigue. Methods: Patient stratification: (1) sustained fatigue (SF, n = 26): latest two Modified Fatigue Impact Scale (MFIS) ⩾ 38; (2) reversible fatigue (RF, n = 25): latest MFIS < 38 and minimum one previous MFIS ⩾ 38; and (3) never fatigued (NF, n = 42): MFIS always < 38 (five assessments minimum). 3T brain magnetic resonance imaging (MRI) was used to perform voxel-wise comparison of fractional anisotropy (FA) between the groups controlling for age, sex, disease duration, physical disability, white matter lesion load (T2LV), and depression. Results: SF and, to a lesser extent, RF patients showed lower FA in multiple brain regions compared to NF patients, independent of age, sex, disease duration, and physical disability. In cingulo-postcommissural-striato-thalamic regions, the differences in FA between SF and NF (but not between RF and NF or SF) patients were independent of T2LV, and in ventromedial prefronto-precommissuro-striatal and temporo-insular areas, independent of T2LV and depression. Conclusion: Damage to ventromedial prefronto-precommissuro-striatal and temporo-insular pathways appears to be a specific substrate of SF in MS.

Preclinical disease activity in multiple sclerosis: A prospective study of cognitive performance prior to first symptom

2016 ◽  
Vol 80 (4) ◽  
pp. 616-624 ◽  
Author(s):  
Marianna Cortese ◽  
Trond Riise ◽  
Kjetil Bjørnevik ◽  
Alok Bhan ◽  
Elisabeth Farbu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prospective Study ◽  
Disease Activity ◽  
Cognitive Performance ◽  
A Prospective Study

Brain atrophy evolution and lesion load accrual in multiple sclerosis: a 2-year follow-up study

2008 ◽  
Vol 15 (2) ◽  
pp. 204-211 ◽  
Author(s):  
G Tedeschi ◽  
D Dinacci ◽  
M Comerci ◽  
L Lavorgna ◽  
G Savettieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Lesion Load ◽  
Whole Brain ◽  
Gray Matter Atrophy

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

scholarly journals Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration

2013 ◽  
Vol 20 (1) ◽  
pp. 72-80 ◽  
Author(s):  
H Kearney ◽  
MA Rocca ◽  
P Valsasina ◽  
L Balk ◽  
J Sastre-Garriga ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Physical Disability ◽  
Disease Duration ◽  
Resonance Imaging ◽  
Lesion Load ◽  
Brain And Spinal Cord

Background: Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease. Objectives: The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS. Methods: Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups). Results: In the binary model, UCCA ( p < 0.01) and T2LV ( p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA ( p < 0.01), T2LV ( p = 0.02) and GMF ( p = 0.04) were independently associated with disability. Conclusions: Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

scholarly journals Unraveling treatment response in multiple sclerosis

Neurology ◽  
2018 ◽  
Vol 92 (4) ◽  
pp. 180-192 ◽  
Author(s):  
Claudio Gasperini ◽  
Luca Prosperini ◽  
Mar Tintoré ◽  
Maria Pia Sormani ◽  
Massimo Filippi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Scoring Systems ◽  
Research Field ◽  
Advantages And Disadvantages ◽  
Long Term Prognosis ◽  
Pharmacologic Treatments ◽  
Monitor Treatment Response ◽  
Quantitative Scoring

Over the last few decades, the improved diagnostic criteria, the wide use of MRI, and the growing availability of effective pharmacologic treatments have led to substantial advances in the management of multiple sclerosis (MS). The importance of early diagnosis and treatment is now well-established, but there is still no consensus on how to define and monitor response to MS treatments. In particular, the clinical relevance of the detection of minimal MRI activity is controversial and recommendations on how to define and monitor treatment response are warranted. An expert panel of the Magnetic Resonance Imaging in MS Study Group analyzed and discussed published studies on treatment response in MS. The evolving concept of no evidence of disease activity and its effect on predicting long-term prognosis was examined, including the option of defining a more realistic target for daily clinical practice: minimal evidence of disease activity. Advantages and disadvantages associated with the use of MRI activity alone and quantitative scoring systems combining on-treatment clinical relapses and MRI active lesions to detect treatment response in the real-world setting were also discussed. While most published studies on this topic involved patients treated with interferon-β, special attention was given to more recent studies providing evidence based on treatment with other and more efficacious oral and injectable drugs. Finally, the panel identified future directions to pursue in this research field.

scholarly journals Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis

2020 ◽  
Vol 7 (4) ◽  
pp. e749 ◽  
Author(s):  
Marie-Christine Reinert ◽  
Pascal Benkert ◽  
Jens Wuerfel ◽  
Zuzanna Michalak ◽  
Esther Ruberte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Single Molecule ◽  
Light Chain ◽  
Interferon Beta ◽  
Class Iii ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker

ObjectiveTo investigate serum neurofilament light chain (sNfL) as a potential biomarker for disease activity and treatment response in pediatric patients with multiple sclerosis (MS).MethodsIn this retrospective cohort study, sNfL levels were measured in a pediatric MS cohort (n = 55, follow-up 12–105 months) and in a non-neurologic pediatric control cohort (n = 301) using a high-sensitivity single-molecule array assay. Association of sNfL levels and treatment and clinical and MRI parameters were calculated.ResultsUntreated patients had higher sNfL levels than controls (median 19.0 vs 4.6 pg/mL; CI [4.732, 6.911]), p < 0.001). sNfL levels were significantly associated with MRI activity (+9.1% per contrast-enhancing lesion, CI [1.045, 1.138], p < 0.001; +0.6% per T2-weighted lesion, CI [1.001, 1.010], p = 0.015). Higher values were associated with a relapse <90 days ago (+51.1%; CI [1.184, 1.929], p < 0.001) and a higher Expanded Disability Status Scale score (CI [1.001, 1.240], p = 0.048). In patients treated with interferon beta-1a/b (n = 27), sNfL levels declined from 14.7 to 7.9 pg/mL after 6 ± 2 months (CI [0.339, 0.603], p < 0.001). Patients with insufficient control of clinical or MRI disease activity under treatment with interferon beta-1a/b or glatiramer acetate who switched to fingolimod (n = 18) showed a reduction of sNfL levels from 16.5 to 10.0 pg/mL 6 ± 2 months after switch (CI [0.481, 0.701], p < 0.001).ConclusionssNfL is a useful biomarker for monitoring disease activity and treatment response in pediatric MS. It is most likely helpful to predict disease severity and to guide treatment decisions in patients with pediatric MS. This study provides Class III evidence that sNfL levels are associated with disease activity in pediatric MS.

scholarly journals A voxel-based morphometry study of disease severity correlates in relapsing— remitting multiple sclerosis

2009 ◽  
Vol 16 (1) ◽  
pp. 45-54 ◽  
Author(s):  
A. Prinster ◽  
M. Quarantelli ◽  
R. Lanzillo ◽  
G. Orefice ◽  
G. Vacca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Disease Duration ◽  
Expanded Disability Status Scale ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing—remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing—remitting multiple sclerosis (Expanded Disability Status Scale range 1.0—6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease.

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