Medical University Graz
General Neurology

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0156 - Serum neurofilament light levels correlate with reduced grey matter volume in advanced multiple sclerosis. (ID 770)

Speakers
Presentation Number
P0156
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Grey matter (GM) pathology is associated with physical and cognitive impairment in patients with multiple sclerosis (pwMS). Increased levels of serum Neurofilament light (sNfL), indicating neuro-axonal damage, have been described in MS and were related to the development of global brain atrophy. However, the relation of sNFL to MRI-based measures of distinct brain volumes, in particular the grey matter, is still poorly investigated.

Objectives

To investigate the association of sNfL with compartmental brain volumes in pwMS in a cross-sectional and longitudinal manner.

Methods

We included 109 pwMS (mean age = 38.1 years, standard deviation (SD) ±11.7 years, 63.3% female) and 17 sex- and age-matched non-inflammatory neurological controls (NC) (mean age = 39.2 years, SD± 9.8 years). The MS cohort consisted of 16 clinically isolated syndrome (CIS), 72 relapsing-remitting MS (RRMS) and 21 progressive MS (PMS) patients. sNfL levels were measured by an ultrasensitive Single Molecule Array (Simoa®). In MS, we assessed whole and compartmental normalized and lesion-filled brain volumes and T2-lesion loads based on 3T MRI data, using T2-FLAIR and T1-weighted 1mm isotropic structural scans, processed with SienaX (part of FSL, fsl.fmrib.ox.ac.uk).

Results

In the entire cohort sNfL levels correlated with age (r = 0.329, p < 0.001). sNfL was significantly elevated in RRMS (p = 0.019) and PMS (p < 0.010) compared to NC, as well as in PMS compared to CIS (p = 0.035). Similarly, we found decreased brain volumes in PMS vs. CIS and RRMS. This was evident for whole brain, white matter (WM), total GM and cortical GM (p ≤ 0.001). Likewise, WM lesion volume was elevated in PMS vs. CIS (p = 0.001) and RRMS (p = 0.022). In deep GM areas, including basal ganglia and thalamus, volumes were decreased in PMS vs. CIS (p = 0.001 and 0.012 respectively) and PMS vs. RRMS (p = 0.038 and 0.015 respectively).
Only in patients with PMS we found sNfL to be negatively correlated with volumes of the whole brain after correcting for age (r = –0.571, p = 0.008). This was mainly driven by the correlation with total GM (r = –0.615, p = 0.004) and cortical GM (r = –0.664, p = 0.001). Regarding deep grey matter, only in PMS we observed a negative correlation of sNfL with basal ganglia volume (r = –0.571, p = 0.011). There was no correlation of sNfL with thalamus volume in any subgroup.

Conclusions

Although sNfL is already increased in earlier phases of MS, our data indicates that its relation to brain tissue damage, in particular GM pathology, might only become apparent in more advanced progressive forms of the disease. Further analysis of longitudinal MRI and clinical data is currently ongoing to confirm and extend our results.

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Presenter Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0156 - Serum neurofilament light levels correlate with reduced grey matter volume in advanced multiple sclerosis. (ID 770)

Speakers
Presentation Number
P0156
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Grey matter (GM) pathology is associated with physical and cognitive impairment in patients with multiple sclerosis (pwMS). Increased levels of serum Neurofilament light (sNfL), indicating neuro-axonal damage, have been described in MS and were related to the development of global brain atrophy. However, the relation of sNFL to MRI-based measures of distinct brain volumes, in particular the grey matter, is still poorly investigated.

Objectives

To investigate the association of sNfL with compartmental brain volumes in pwMS in a cross-sectional and longitudinal manner.

Methods

We included 109 pwMS (mean age = 38.1 years, standard deviation (SD) ±11.7 years, 63.3% female) and 17 sex- and age-matched non-inflammatory neurological controls (NC) (mean age = 39.2 years, SD± 9.8 years). The MS cohort consisted of 16 clinically isolated syndrome (CIS), 72 relapsing-remitting MS (RRMS) and 21 progressive MS (PMS) patients. sNfL levels were measured by an ultrasensitive Single Molecule Array (Simoa®). In MS, we assessed whole and compartmental normalized and lesion-filled brain volumes and T2-lesion loads based on 3T MRI data, using T2-FLAIR and T1-weighted 1mm isotropic structural scans, processed with SienaX (part of FSL, fsl.fmrib.ox.ac.uk).

Results

In the entire cohort sNfL levels correlated with age (r = 0.329, p < 0.001). sNfL was significantly elevated in RRMS (p = 0.019) and PMS (p < 0.010) compared to NC, as well as in PMS compared to CIS (p = 0.035). Similarly, we found decreased brain volumes in PMS vs. CIS and RRMS. This was evident for whole brain, white matter (WM), total GM and cortical GM (p ≤ 0.001). Likewise, WM lesion volume was elevated in PMS vs. CIS (p = 0.001) and RRMS (p = 0.022). In deep GM areas, including basal ganglia and thalamus, volumes were decreased in PMS vs. CIS (p = 0.001 and 0.012 respectively) and PMS vs. RRMS (p = 0.038 and 0.015 respectively).
Only in patients with PMS we found sNfL to be negatively correlated with volumes of the whole brain after correcting for age (r = –0.571, p = 0.008). This was mainly driven by the correlation with total GM (r = –0.615, p = 0.004) and cortical GM (r = –0.664, p = 0.001). Regarding deep grey matter, only in PMS we observed a negative correlation of sNfL with basal ganglia volume (r = –0.571, p = 0.011). There was no correlation of sNfL with thalamus volume in any subgroup.

Conclusions

Although sNfL is already increased in earlier phases of MS, our data indicates that its relation to brain tissue damage, in particular GM pathology, might only become apparent in more advanced progressive forms of the disease. Further analysis of longitudinal MRI and clinical data is currently ongoing to confirm and extend our results.

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