scholarly journals Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis

2021 ◽  
pp. 135245852110100
Author(s):  
Zoë YGJ van Lierop ◽  
Luuk Wieske ◽  
Marleen JA Koel-Simmelink ◽  
Madhurima Chatterjee ◽  
Iris Dekker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Odds Ratio ◽  
Prognostic Biomarker ◽  
Disability Progression ◽  
Lower Baseline ◽  
Relapsing Remitting ◽  
Natalizumab Treatment

Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). Objective: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. Methods: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. Results: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04–1.45) ( p = 0.017) for progression during follow-up. Conclusion: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS.

scholarly journals Evolution of tumefactive lesions in multiple sclerosis: A 12-year study with serial imaging in a single patient

2013 ◽  
Vol 19 (11) ◽  
pp. 1539-1543 ◽  
Author(s):  
Vasiliki N Ikonomidou ◽  
Nancy D Richert ◽  
Alexander Vortmeyer ◽  
Fernanda Tovar-Moll ◽  
Bibiana Bielekova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetization Transfer ◽  
Magnetic Resonance Images ◽  
Single Patient ◽  
Disability Progression ◽  
Term Evolution ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

We describe the acute presentation and the long-term evolution of recurrent tumefactive lesions (TLs) in a patient with relapsing–remitting multiple sclerosis. Five TLs occurred on three different occasions over a period of 12 years and these were followed by 73 serial magnetic resonance images (MRI). TL evolution was described by means of magnetization transfer imaging (MTI) and cerebrospinal fluid tissue specific imaging (TSI) over the follow-up period. During the study period, the patient had three clinical relapses with only minimal disability progression. MTI demonstrated that only the peripheral portion of each TL reverted to pre-lesional MT ratios within six months’ post-enhancement. Recurring TLs may present a similar pattern of evolution that may be associated with a long-term favourable clinical outcome.

Association of Spectral-Domain OCT With Long-term Disability Worsening in Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011788
Author(s):  
Jeffrey Lambe ◽  
Kathryn C. Fitzgerald ◽  
Olwen C. Murphy ◽  
Angeliki G. Filippatou ◽  
Elias S. Sotirchos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Spectral Domain ◽  
Inner Plexiform Layer ◽  
Lower Baseline ◽  
Edss Score ◽  
Sd Oct

Objective:To evaluate whether a retinal spectral-domain optical coherence tomography (SD-OCT) assessment at baseline is associated with long-term disability worsening in people with multiple sclerosis (PwMS), we performed SD-OCT and Expanded Disability Status Scale (EDSS) assessments among 132 PwMS at baseline and at a median of 10 years later.Methods:In this prospective, longitudinal study, participants underwent SD-OCT, EDSS, and visual acuity (VA) assessments at baseline and at follow-up. Statistical analyses were performed using generalized linear regression models, adjusted for age, sex, race, MS subtype, and baseline disability. We defined clinically meaningful EDSS worsening as an increase of ≥2.0 if baseline EDSS score was <6.0, or an increase of ≥1.0 if baseline EDSS score was ≥6.0.Results:132 PwMS (mean age: 43 years; n=106 patients with relapsing remitting MS) were included in analyses. Median duration of follow-up was 10.4 years. In multivariable models excluding eyes with prior optic neuritis, relative to patients with an average baseline ganglion cell+inner plexiform layer (GCIPL) thickness ≥70µm (the mean GCIPL thickness of all eyes at baseline), an average baseline GCIPL thickness <70µm was associated with a 4-fold increased odds of meaningful EDSS worsening (adjusted odds ratio: 3.97; 95% CI: 1.24-12.70; p=0.02), and an almost 3-fold increased odds of low-contrast VA worsening (adjusted odds ratio: 2.93; 95% CI: 1.40-6.13; p=0.04).Conclusions:Lower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS. Accordingly, SD-OCT at a single time-point may help to guide therapeutic decision making among individual PwMS.Classification of Evidence:This study provides Class I evidence that lower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS.

Long-term disability outcomes in relapsing-remitting multiple sclerosis: a 10-year follow-up study

2019 ◽  
Vol 40 (8) ◽  
pp. 1627-1636 ◽  
Author(s):  
Jelena Drulovic ◽  
Jovana Ivanovic ◽  
Sarlota Mesaros ◽  
Vanja Martinovic ◽  
Darija Kisic-Tepavcevic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Follow Up Study ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression

2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
In Cis

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

scholarly journals Association of Gray Matter Atrophy Patterns With Clinical Phenotype and Progression in Multiple Sclerosis

Neurology ◽  
2021 ◽  
Vol 96 (11) ◽  
pp. e1561-e1573
Author(s):  
Maria A. Rocca ◽  
Paola Valsasina ◽  
Alessandro Meani ◽  
Claudio Gobbi ◽  
Chiara Zecca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Odds Ratio ◽  
Disease Duration ◽  
Clinical Phenotype ◽  
Area Under The Curve ◽  
Disease Phenotypes ◽  
Relapsing Remitting ◽  
Almost All ◽  
Clinical Worsening

ObjectivesGay matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes.MethodsClinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 patients with MS (34 with clinically isolated syndrome [CIS], 226 with relapsing-remitting MS [RRMS], 95 with secondary progressive MS [SPMS], and 43 with primary progressive MS [PPMS]). Fifty-seven HCs and 144 with MS underwent 1-year follow-up. Baseline GM loss, atrophy progression, and correlations with disability and 1-year clinical worsening were assessed.ResultsSBM identified 26 cerebellar, subcortical, sensory, motor, and cognitive GM components. GM atrophy was found in patients with MS vs HCs in almost all components (p range <0.001–0.04). Compared to HCs, patients with CIS showed circumscribed subcortical, cerebellar, temporal, and salience GM atrophy, while patients with RRMS exhibited widespread GM atrophy. Cerebellar, subcortical, sensorimotor, salience, and frontoparietal GM atrophy was found in patients with PPMS vs HCs and in patients with SPMS vs those with RRMS. At 1 year, 21 (15%) patients had clinically worsened. GM atrophy progressed in MS in subcortical, cerebellar, sensorimotor, and fronto-temporo-parietal components. Baseline higher disability was associated (R2 = 0.65) with baseline lower normalized brain volume (β = −0.13, p = 0.001), greater sensorimotor GM atrophy (β = −0.12, p = 0.002), and longer disease duration (β = 0.09, p = 0.04). Baseline normalized GM volume (odds ratio 0.98, p = 0.008) and cerebellar GM atrophy (odds ratio 0.40, p = 0.01) independently predicted clinical worsening (area under the curve 0.83).ConclusionGM atrophy differed across disease phenotypes and progressed at 1 year in MS. In addition to global atrophy measures, sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening.

scholarly journals Leukocyte telomere length in patients with multiple sclerosis and its association with clinical phenotypes

2020 ◽  
Author(s):  
Michael Hecker ◽  
Brit Fitzner ◽  
Kathrin Jäger ◽  
Jan Bühring ◽  
Margit Schwartz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Telomere Shortening ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Age And Sex

AbstractAging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS.We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS) and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex.The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis.Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.Research in contextEvidence before this studyThere is a growing research interest in the relationship between age and the pathophysiology and clinical presentation of multiple sclerosis (MS). Telomere shortening is a hallmark of biological aging. However, the role of telomeres in this chronic immune-mediated neurodegenerative disease has not yet been widely studied. Two research groups provided evidence that the telomeres of immune cells in the peripheral blood are shorter in patients with MS than in healthy subjects.Added value of this studyWe found that leukocytes from patients with relapsing-remitting MS (RRMS) are characterized by relatively short telomere lengths (TL). On average, we observed 18% shorter TL in the RRMS patient cohort (n=40) than in the age- and sex-matched healthy control cohort (n=60). We further analyzed the association of TL and long-term clinical outcomes. RRMS patients with shorter TL had a higher rate of converting to secondary progressive MS over a 10-year follow-up period.Implications of all the available evidenceAs we and others have shown, TL are generally shorter in MS patients and associated with disease progression, independent of age. These findings suggest a link between biological aging and the heterogeneous clinical course of MS patients. It currently remains unclear whether shortened telomeres in MS are a cause or a consequence of the pathophysiological processes. Further studies with larger patient cohorts and different cell populations will be needed to expand our knowledge of age-related disease mechanisms and the use of TL as a biomarker in MS.

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