The Effect of Aerobic Exercise on Neurofilament Light Chain and Glial Fibrillary Acidic Protein Level in Patients with Relapsing Remitting Type Multiple Sclerosis

2021 ◽  
pp. 103219
Author(s):  
Zubeyde ERCAN ◽  
Furkan BILEK ◽  
Caner Feyzi DEMIR
Keyword(s):  
Multiple Sclerosis ◽  
Glial Fibrillary Acidic Protein ◽  
Aerobic Exercise ◽  
Light Chain ◽  
Protein Level ◽  
Acidic Protein ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Relapsing Remitting

scholarly journals Long-term prognostic value of longitudinal measurements of blood neurofilament levels

2020 ◽  
Vol 7 (5) ◽  
pp. e856 ◽  
Author(s):  
Dieter A. Häring ◽  
Harald Kropshofer ◽  
Ludwig Kappos ◽  
Jeffrey A. Cohen ◽  
Anuja Shah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Light Chain ◽  
Prognostic Value ◽  
Long Term Outcomes ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Longitudinal Measurements ◽  
Relapsing Remitting ◽  
Edss Score

ObjectiveTo assess the long-term prognostic value of an integral of longitudinal measurements of plasma neurofilament light chain levels (NfLlong) over 12 and 24 months vs single neurofilament light chain (NfL) measurements in patients with relapsing-remitting MS (RRMS) and its additional value when combined with clinical and MRI measures.MethodsThis analysis included continuously fingolimod-treated patients with RRMS from the 24-month FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS)/12-month Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting Multiple Sclerosis (TRANSFORMS) phase 3 trials and their long-term extension, LONGTERMS. Patients were classified into high (≥30 pg/mL, n = 110) and low (<30 pg/mL, n = 164) NfL categories based on the baseline (BL) NfL value or the geometric mean NfLlong calculated over 12 and 24 months to predict disability-related outcomes and brain volume loss (BVL). The additional prognostic value of NfL was quantified using the area under the receiver operating characteristic (ROC) curve.ResultsA single high (vs low) NfL measure at BL was prognostic of a higher risk of reaching Expanded Disability Status Scale (EDSS) score ≥4 earlier (hazard ratio [HR] = 2.19; 95% CI = 1.21–3.97) and higher BVL over 120 months (difference: −1.12%; 95% CI = −2.07 to −0.17). When NfLlong was measured over 24 months, high NfL was associated with a higher risk of reaching EDSS score ≥4 (HR = 7.91; 95% CI = 2.99–20.92), accelerated 6-month confirmed disability worsening (HR = 3.14; 95% CI = 1.38–7.11), and 20% worsening in the Timed 25-Foot Walk Test (HR = 3.05; 95% CI = 1.38–6.70). Area under the ROC curve was consistently highest in models combining NfL with clinical and MRI measures.ConclusionsNfLlong had a higher prognostic value than single NfL assessments on long-term outcomes in RRMS. Combining it with clinical and MRI measures increased sensitivity and specificity to predict long-term disease outcomes.Classification of evidenceThis study provides Class I evidence that NfLlong was more strongly associated with long-term outcomes than single NfL assessments in patients with RRMS.

Absence of attack-independent neuroaxonal injury in MOG antibody-associated disease: Longitudinal assessment of serum neurofilament light chain

2021 ◽  
pp. 135245852110637
Author(s):  
Jae-Won Hyun ◽  
So Yeon Kim ◽  
Yeseul Kim ◽  
Na Young Park ◽  
Ki Hoon Kim ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Single Molecule ◽  
Light Chain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Acidic Protein ◽  
Healthy Controls ◽  
Longitudinal Assessment ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD.

scholarly journals Blood neurofilament light chain as a biomarker of MS disease activity and treatment response

Neurology ◽  
2019 ◽  
Vol 92 (10) ◽  
pp. e1007-e1015 ◽  
Author(s):  
Jens Kuhle ◽  
Harald Kropshofer ◽  
Dieter A. Haering ◽  
Uma Kundu ◽  
Rolf Meinert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Light Chain ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis.MethodsWe measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-β-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes.ResultsAt baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51–4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67–3.83]; p < 0.0001), brain volume loss (difference in means: −0.78% [−1.02 to −0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97–3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656–0.813] and IFN 0.789 [0.704–0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552–0.714] and IFN 0.794 [0.705–0.894]; p < 0.001, both studies at all assessments).ConclusionsBlood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response.

scholarly journals Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL

2020 ◽  
Author(s):  
Chen Chih-Hao ◽  
Yu-Wen Cheng ◽  
Ya-Fang Chen ◽  
Sung-Chun Tang ◽  
Jiann-Shing Jeng
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Light Chain ◽  
Odds Ratio ◽  
Acidic Protein ◽  
White Matter Hyperintensity ◽  
Stroke Recurrence ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers

Abstract Background Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. Methods Sixty-three CADASIL patients (mean age 58.9±9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. Results Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. Within a mean follow-up period of 3.1 Common.EditSubmissionSteps.Transform.EquationText 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19–3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21–6.53) predicted incident ICH. Conclusions In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.

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