scholarly journals Serum Neurofilament Light Chain Levels are Associated with Lower Thalamic Perfusion in Multiple Sclerosis

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 685
Author(s):  
Dejan Jakimovski ◽  
Niels Bergsland ◽  
Michael G. Dwyer ◽  
Deepa P. Ramasamy ◽  
Murali Ramanathan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Cerebral Blood Volume ◽  
Mean Transit Time ◽  
Dynamic Susceptibility ◽  
Linear Regression Models ◽  
Dynamic Susceptibility Contrast ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Normal Appearing White Matter

Both perfusion-weighted imaging (PWI) measures and serum neurofilament light (sNfL) chain levels have been independently associated with disability in multiple sclerosis (MS) patients. This study aimed to determine whether these measures are correlated to each other or independently describe different MS processes. For this purpose, 3T MRI dynamic susceptibility contrast (DSC)–PWI and single-molecule assay (Simoa)-based sNfL methods were utilized when investigating 86 MS patients. The perfusion measures of mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were derived for the normal-appearing whole brain (NAWB), the normal-appearing white matter (NAWM), the gray matter (GM), the deep GM (DGM), and the thalamus. The normalized CBV and CBF (nCBV and nCBV) were calculated by dividing by the corresponding NAWM measure. Age- and sex-adjusted linear regression models were used to determine associations between the DSC–PWI and sNfL results. False discovery rate (FDR)-adjusted p-values < 0.05 were considered statistically significant. A greater age and thalamic MTT were independently associated with higher sNfL levels (p < 0.001 and p = 0.011) and explained 36.9% of sNfL level variance. NAWM MTT association with sNfL levels did not survive the FDR correction. In similar models, a lower thalamic nCBF and nCBV were both associated with greater sNfL levels (p < 0.001 and p = 0.022), explaining 37.8% and 44.7% of the variance, respectively. In conclusion, higher sNfL levels were associated with lower thalamic perfusion.

scholarly journals Heterogeneity of Cortical Lesions in Multiple Sclerosis: An MRI Perfusion Study

2012 ◽  
Vol 33 (3) ◽  
pp. 457-463 ◽  
Author(s):  
Denis Peruzzo ◽  
Marco Castellaro ◽  
Massimiliano Calabrese ◽  
Elisa Veronese ◽  
Francesca Rinaldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Neurons ◽  
Cerebral Blood Volume ◽  
Mean Transit Time ◽  
Small Population ◽  
Dynamic Susceptibility ◽  
Cortical Lesions ◽  
Dynamic Susceptibility Contrast ◽  
Dsc Mri ◽  
Susceptibility Contrast

In this study, dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) was used to quantify the cerebral blood flow (CBF), the cerebral blood volume (CBV), and the mean transit time (MTT) and to analyze the changes in cerebral perfusion associated with the cortical lesions in 44 patients with relapsing-remitting multiple sclerosis. The cortical lesions showed a statistically significant reduction in CBF and CBV compared with the normal-appearing gray matter, whereas there were no significant changes in the MTT. The reduced perfusion suggests a reduction of metabolism because of the loss of cortical neurons. A small population of outliers showing an increased CBF and/or CBV has also been detected. The presence of hyperperfused outliers may imply that perfusion could evolve during inflammation. These findings show that perfusion is altered in cortical lesions and that DSC-MRI can be a useful tool to investigate more deeply the evolution of cortical lesions in multiple sclerosis.

scholarly journals The effect of carotid artery stenting on capillary transit time heterogeneity in patients with carotid artery stenosis

2018 ◽  
Vol 3 (3) ◽  
pp. 263-271 ◽  
Author(s):  
Ethem M Arsava ◽  
Mikkel B Hansen ◽  
Berkan Kaplan ◽  
Ahmet Peker ◽  
Rahsan Gocmen ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Transit Time ◽  
Carotid Artery Stenting ◽  
Cerebral Blood Volume ◽  
Mean Transit Time ◽  
Oxygen Extraction Fraction ◽  
Consecutive Series ◽  
Dynamic Susceptibility ◽  
Dynamic Susceptibility Contrast ◽  
Vascular Events

Introduction Carotid revascularisation improves haemodynamic compromise in cerebral circulation as an additional benefit to the primary goal of reducing future thromboembolic risk. We determined the effect of carotid artery stenting on cerebral perfusion and oxygenation using a perfusion-weighted MRI algorithm that is based on assessment of capillary transit-time heterogeneity together with other perfusion and metabolism-related metrics. Patients and methods A consecutive series of 33 patients were evaluated by dynamic susceptibility contrast perfusion-weighted MRI prior to and within 24 h of the endovascular procedure. The level of relative change induced by stenting, and relationship of these changes with respect to baseline stenosis degree were analysed. Results Stenting led to significant increase in cerebral blood flow ( p < 0.001), and decrease in cerebral blood volume ( p = 0.001) and mean transit time ( p < 0.001); this was accompanied by reduction in oxygen extraction fraction ( p < 0.001) and capillary transit-time heterogeneity ( p < 0.001), but an overall increase in relative capillary transit-time heterogeneity (RTH: CTH divided by MTT; p = 0.008). No significant change was observed with respect to cerebral metabolic rate of oxygen. The median volume of tissue with MTT > 2s decreased from 24 ml to 12 ml ( p = 0.009), with CTH > 2s from 29 ml to 19 ml ( p = 0.041), and with RTH < 0.9 from 61 ml to 39 ml ( p = 0.037) following stenting. These changes were correlated with the baseline degree of stenosis. Discussion: Stenting improved the moderate stage of haemodynamic compromise at baseline in our cohort. The decreased relative transit-time heterogeneity, which increases following stenting, is probably a reflection of decreased functional capillary density secondary to chronic hypoperfusion induced by the proximal stenosis. Conclusion: Carotid artery stenting, is not only important for prophylaxis of future vascular events, but also is critical for restoration of microvascular function in the cerebral tissue.

scholarly journals Intra-tumoural perfusion habitats showed prognostic value in glioblastoma patients

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv3-iv3
Author(s):  
Chao Li ◽  
Chang Sun ◽  
Shuo Wang ◽  
Stephen Price
Keyword(s):  
Cerebral Blood Volume ◽  
Cox Regression ◽  
Mean Transit Time ◽  
Tumour Microenvironment ◽  
Dynamic Susceptibility ◽  
Dynamic Susceptibility Contrast ◽  
Post Contrast ◽  
Dsc Mri ◽  
Contrast Enhanced ◽  
Susceptibility Contrast

Abstract The perfusion within glioblastoma is associated with tumour microenvironment and may create invasive tumor habitats that could potentially be revealed by perfusion imaging. The purpose of this study is to characterize the peritumoural habitats of glioblastoma for treatment target. Dynamic susceptibility contrast-enhancement (DSC) MRI was acquired pre-operatively on 115 newly-diagnosed glioblastoma patients. All images were co-registered to post-contrast T1-weighted images. The relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated from the DSC images. The contrast-enhanced and peritumoural tumor regions were semi-automatically segmented from the post-contrast T1-weighted and FLAIR images. To delineate the habitats of different perfusion levels, a two clusters mixture model with Gaussian distribution was fitted to the rCBV, rCBF, and MTT within both contrast-enhanced and peritumoural regions. Perfusion parameters of the identified habitats were compared, and the prognostic values of habitats were investigated using survival analysis. The results showed that although non-enhanced, the peritumoral high perfusion (PHP) habitat demonstrated similar perfusion level with the contrast high perfusion (CHP) habitat, with similar rCBV (PHP: 1.13 ± 0.18, 95% CI [1.10, 1.15]; CHP: 1.21 ± 0.25, 95% CI [1.16, 1.21]) and rCBF (PHP: 1.08 ± 0.23, 95% CI [1.05, 1.08]; CHP: 1.08 ± 0.19, 95% CI [1.05, 1.08]). Multivariate Cox regression showed that the volumes of both habitats were associated with worse patient overall survival (PHP: P = 0.032; HR= 7.09; CHP: P = 0.008; HR= 12.01). Our results suggest that the intra-tumoural perfusion habitats may potentially offer treatment targets.

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 Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

2021 ◽  
Author(s):  
Henning H. Rise ◽  
Synne Brune ◽  
Claudia Chien ◽  
Tone Berge ◽  
Steffan D. Bos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Brain Network ◽  
Axonal Damage ◽  
Base Line ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Random Factor ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

AbstractThe pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient’s white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, β = 0.03, p = 0.02), age (t = 5.01, β = 0.32, p < 5.5 × 10−7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, β = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = −1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Nelly Siller ◽  
Jens Kuhle ◽  
Muthuraman Muthuraman ◽  
Christian Barro ◽  
Timo Uphaus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Axonal Damage ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Parenchymal

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.

scholarly journals Implications of extreme serum neurofilament light chain levels for the management of patients with relapsing multiple sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110019
Author(s):  
Sinah Engel ◽  
Maria Protopapa ◽  
Falk Steffen ◽  
Vakis Papanastasiou ◽  
Christoforos Nicolaou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Single Molecule ◽  
Light Chain ◽  
Clinical Symptoms ◽  
Threshold Value ◽  
Sample Collection ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Mean

Background: Serum neurofilament light chain (sNfL) is a promising biomarker to complement the decision-making process in multiple sclerosis (MS) patients. However, although sNfL levels are able to detect disease activity and to predict future disability, the growing evidence has not yet been translated into practicable recommendations for an implementation into clinical routine. Methods: The observation of a patient with extensive inflammatory activity in magnetic resonance imaging (MRI) along with an extremely high sNfL level in the absence of any clinical symptoms prompted us to investigate common characteristics of our MS patients with the highest sNfL levels in a retrospective cohort study. The 97.5th percentile was chosen as a cut-off value because the mean sNfL level of the resulting extreme neurofilament light chain (NfL) cohort corresponded well to the sNfL level of the presented case. Patient characterization included clinical and MRI assessment with a focus on disease activity markers. sNfL levels were determined by single molecule array. Results: The 97.5th percentile of our MS cohort (958 sNfL measurements in 455 patients) corresponded to a threshold value of 46.1 pg/ml. The mean sNfL level of the extreme sNfL cohort ( n = 24) was 95.6 pg/ml (standard deviation 68.4). Interestingly, only 15 patients suffered from a relapse at the time point of sample collection, whereas nine patients showed no signs of clinical disease activity. sNfL levels of patients with and without relapse did not differ [median 81.3 pg/ml (interquartile range [IQR] 48.0–128) versus 80.2 pg/ml (IQR 46.4–97.6), p = 0.815]. The proportion of patients with contrast-enhancing lesions was high and also did not differ between patients with and without relapse (92.9% versus 87.5%, p = 0.538); 78.9% of the patients not receiving a high-efficacious therapy had ongoing disease activity during a 2-year follow-up. Conclusion: Extremely high sNfL levels are indicative of subclinical disease activity and might complement treatment decisions in ambiguous cases.

scholarly journals Serum NfL levels in the first five years predict 10-year thalamic fraction in patients with MS

2022 ◽  
Vol 8 (1) ◽  
pp. 205521732110693
Author(s):  
Hrishikesh Lokhande ◽  
Mattia Rosso ◽  
Shahamat Tauhid ◽  
Renxin Chu ◽  
Brian C. Healy ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Cortical Thickness ◽  
Single Molecule ◽  
Regression Models ◽  
Prognostic Biomarker ◽  
Disease Onset ◽  
Linear Regression Models ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volumes

Background Serum neurofilament light chain (sNfL) levels are associated with relapses, MRI lesions, and brain volume in multiple sclerosis (MS). Objective To explore the value of early serum neurofilament light (sNfL) measures in prognosticating 10-year regional brain volumes in MS. Methods Patients with MS enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study within five years of disease onset who had annual blood samples from years 1–10 (n = 91) were studied. sNfL was measured with a single molecule array (SIMOA) assay. We quantified global cortical thickness and normalized deep gray matter (DGM) volumes (fractions of the thalamus, caudate, putamen, and globus pallidus) from high-resolution 3 T MRI at 10 years. Correlations between yearly sNfL levels and 10-year MRI outcomes were assessed using linear regression models. Results sNfL levels from years 1 and 2 were associated with 10-year thalamus fraction. Early sNfL levels were not associated with 10-year putamen, globus pallidus or caudate fractions. At 10 years, cortical thickness was not associated with early sNfL levels, but was weakly correlated with total DGM fraction. Conclusions Early sNfL levels correlate with 10-year thalamic volume, supporting its role as a prognostic biomarker in MS.

scholarly journals Impact of Dietary Intervention on Serum Neurofilament Light Chain in Multiple Sclerosis

2021 ◽  
Vol 9 (1) ◽  
pp. e1102
Author(s):  
Markus Bock ◽  
Falk Steffen ◽  
Frauke Zipp ◽  
Stefan Bittner
Keyword(s):  
Multiple Sclerosis ◽  
Ketogenic Diet ◽  
Single Molecule ◽  
Light Chain ◽  
Dietary Intervention ◽  
Controlled Trial ◽  
Trial Registration ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Impact

Background and ObjectivesAdapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for multiple sclerosis (MS), but information on their impact on neuroaxonal damage is lacking. Thus, we explored the impact of diets on serum neurofilament light chain (sNfL) levels in patients with relapsing-remitting MS.MethodsWe retrospectively evaluated a prospective randomized controlled trial of 60 patients with MS who were on a common diet or ketogenic diet or fasting. We examined sNfL levels of 40 participants at baseline and at the end of the study after 6 months using single molecule array assay.ResultssNfL levels were investigated in 9 controls, 14 participants on CR, and 17 participants on AKD. Correlation analysis showed an association of sNfL with age and disease duration; an association was also found between sNfL and the Multiple Sclerosis Functional Composite. AKD significantly reduced sNfL levels at 6 months compared with the common diet group (p = 0.001).DiscussionFor clinical or study use, consider that AKD may incline sNfL levels independent of relapse activity up to 3 months after initiation. At 6 months, AKD, which complements current therapies, reduced sNfL levels, therefore suggesting potential neuroprotective effects in MS. A single cycle of seven-day fasting did not affect sNfL. AKD may be an addition to the armamentarium to help clinicians support patients with MS in a personalized manner with tailored diet strategies.Trial Registration InformationClinical trial registration number NCT01538355.

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