Are neurofilaments valuable biomarkers for long-term disease prognostication in MS?

Khalil, Michael

doi:10.1177/1352458518791518

Cited by 11 publications

(8 citation statements)

References 11 publications

(27 reference statements)

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“…Several studies highlighted the relevance of sNfL levels to reflect ongoing neuroinflammation as well as neurodegeneration in patients with MS. 8,37 In our cohort, only patients with highly active relapsing-remitting MS disease course were included.…”

Section: Discussionmentioning

confidence: 99%

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Akgün

Kretschmann

Haase

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo evaluate individual neurofilament light chain (NfL) variation over the time of disease course and the potential of NfL measurement to predict treatment response in patients with MS.MethodsWe investigated 15 patients with MS after immune reconstitution treatment with alemtuzumab (ATZ). Monthly serum NfL (sNFL) measurements were correlated with Expanded Disability Status Scale (EDSS), MRI, and relapse activity over an observational period of up to 102 months.ResultsBefore ATZ, sNfL was significantly increased in correlation with previous relapse/MRI activity. After ATZ, sNfL decreased quickly within the first 6 months. In patients classified as NEDA-3, sNfL declined and persisted at an individual low steady-state level of <8 pg/mL. During follow-up, 34 sNfL peaks with a >20 fold increase could be detected, which were associated with clinical or MRI disease activity. Even patient-reported relapse-suspicious symptoms, which have not been confirmed because relapses were accompanied by sNfL, increase, proposing sNfL assessment as a marker for relapse activity. sNfL started to increase earliest 5 months before, peaked at clinical onset, and recovered within 4–5 months. sNfL presented at higher levels in active patients requiring ATZ retreatment compared with responder patients. During 2 documented pregnancies, sNfL was at a low level, whereas a postpartum transient sNfL increase was seen without any signs of activity.ConclusionsThis study applied a long-term high-frequency sNfL assessment in an ATZ-treated cohort, allowing a holistic profiling on the individual level and highlighted that sNfL can eminently complement the individual clinical and MRI monitoring in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Akgün

Kretschmann

Haase

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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“…Overall, the determination of serum NFL concentration, which does not necessarily require a lumbar puncture but can be now measured in the blood, seems to correlate with many clinical and magnetic tomographic characteristics of MS [96, 104, 105]. A future establishment as a prognostic biomarker in clinical practice is therefore conceivable.…”

Section: Molecular Biomarkers For Ms Prognosismentioning

confidence: 99%

Molecular biomarkers in multiple sclerosis

Ziemssen

Akgün

Brück

2019

J Neuroinflammation

181

141

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Multiple sclerosis (MS) is an inflammatory-neurodegenerative disease of the central nervous system presenting with significant inter- and intraindividual heterogeneity. However, the application of clinical and imaging biomarkers is currently not able to allow individual characterization and prediction. Complementary, molecular biomarkers which are easily quantifiable come from the areas of immunology and neurobiology due to the causal pathomechanisms and can excellently complement other disease characteristics. Only a few molecular biomarkers have so far been routinely used in clinical practice as their validation and transfer take a long time. This review describes the characteristics that an ideal MS biomarker should have and the challenges of establishing new biomarkers. In addition, clinically relevant and promising biomarkers from the blood and cerebrospinal fluid are presented which are useful for MS diagnosis and prognosis as well as for the assessment of therapy response and side effects.

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“…Elevated sNfL levels have been shown to reflect acute axonal damage during active inflammation,9 and increasing evidence support the use of sNfL to monitor short-term disease activity, treatment response and disability progression 10. Whether sNfL levels also predict disease progression and neurodegeneration over several years, and even decades, is less clear 6 10–12. Associations between sNfL and long-term disability progression are not consistent,13 14 and although some studies have found higher sNfL levels to be associated with brain13 15 16 and GM atrophy,17–19 studies with extensive follow-up time are few, especially studies considering GM atrophy 17 19.…”

Section: Introductionmentioning

confidence: 99%

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study

Lie

Kaçar

Wesnes

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundThe predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear.ObjectiveInvestigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years.Methods85 patients, originally enrolled in a multicentre, randomised trial of ω−3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer.ResultsHigher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (β=−0.399, p=0.040) and deep (β=−0.556, p=0.010) GM volume, lower mean cortical thickness (β=−0.581, p=0.010) and higher T2 lesion count (β=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (β=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression.ConclusionHigher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.

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Are neurofilaments valuable biomarkers for long-term disease prognostication in MS?

Cited by 11 publications

References 11 publications

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Molecular biomarkers in multiple sclerosis

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study

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