Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease

Peters, Nils; Leijsen, Esther van; Tuladhar, Anil M.; Barro, Christian; Konieczny, M.; Ewers, Michael; Lyrer, Philippe; Engelter, Stefan T.; Kuhle, Jens; Duering, Marco; Leeuw, Frank‐Erik de

doi:10.5853/jos.2019.02845

Cited by 34 publications

(46 citation statements)

References 26 publications

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“…21 It is also broadly consistent with recent evidence in mild SVD showing baseline NfL predicts risk of future lacunes. 24 Why there was no significant change in NfL over 3 years in SCANS is uncertain and may be explained by dynamic changes in NfL post stroke. 25 26 Findings from patients with small subcortical infarcts demonstrated that NfL was elevated but eventually returned to normal levels after 15 months.…”

Section: Discussionmentioning

confidence: 99%

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Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

Egle

Loubière

Maceski

et al. 2021

J Neurol Neurosurg Psychiatry

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ObjectivesSerum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be used to predict outcome, studies are required to demonstrate baseline NfL predicts future dementia risk. Furthermore, if it is to be used as a surrogate marker in clinical trials, change in NfL over time periods typical of a clinical trial must be linked to clinical progression. In a longitudinal study of patients with lacunar stroke and confluent white matter hyperintensities, we determined whether both baseline, and change, in NfL levels were linked to changes in MRI markers, cognitive decline and dementia risk.MethodsPatients underwent MRI, cognitive testing and blood taking at baseline and annually for 3 years. Clinical and cognitive follow-up continued for 5 years.ResultsNfL data were available for 113 subjects for baseline analysis, and 90 patients for the longitudinal analysis. Baseline NfL predicted cognitive decline (global cognition β=−0.335, SE=0.094, p=0.001) and risk of converting to dementia (HR=1.676 (95% CI 1.183 to 2.373), p=0.004). In contrast to imaging, there was no change in NfL values over the follow-up period.ConclusionsBaseline NfL predicts changes in MRI markers, cognitive decline and dementia rate over a 5 years follow-up period in SVD, suggesting NfL may be a useful prognostic marker. However, change in NfL values was not detected, and therefore NfL may not be a useful surrogate marker in clinical trials in SVD.

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Section: Discussionmentioning

confidence: 99%

“… 21 It is also broadly consistent with recent evidence in mild SVD showing baseline NfL predicts risk of future lacunes. 24 …”

Section: Discussionmentioning

confidence: 99%

Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

Egle

Loubière

Maceski

et al. 2021

J Neurol Neurosurg Psychiatry

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“…Elevated serum NfL levels at 6 months after stroke positively correlate with an MRI‐based quantitative measure of secondary neurodegeneration [12]. As an association between plasma NfL levels and time since stroke was not found, the elevated plasma NfL levels in our study population conceivably reflect stroke‐induced secondary neurodegeneration, as well as age‐related changes in the white matter and other ongoing neurodegenerative processes such as those leading to Alzheimer's disease [21], or small vessel disease [22,23].…”

Section: Discussionmentioning

confidence: 94%

Plasma neurofilament light chain levels predict improvement in late phase after stroke

Stokowska

Käll

Blomstrand

et al. 2021

Euro J of Neurology

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Background and purpose Although functional recovery is most pronounced in the first 6 months after stroke, improvement is possible also in the late phase. The value of plasma neurofilament light chain (NfL), a biomarker of axonal injury and secondary neurodegeneration, was explored for the prediction of functional improvement in the late phase after stroke. Methods Baseline plasma NfL levels were measured in 115 participants of a trial on the efficacy of multimodal rehabilitation in the late phase after stroke. The association between NfL levels, impairment in balance, gait and cognitive domains, and improvement 3 and 9 months later was determined. Results Plasma NfL levels were associated with the degree of impairment in all three domains. Individuals with meaningful improvement in balance and gait capacity had higher plasma NfL levels compared with non‐improvers (p = 0.001 and p = 0.018, respectively). Higher NfL levels were associated with improvement in balance (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.35–4.27, p = 0.004) and gait (OR 2.27, 95% CI 1.25–4.32, p = 0.009). Elevated plasma NfL levels showed a positive predictive value for cognitive improvement, and this effect was specific for the intervention targeting the cognitive domain. The association of NfL levels with cognitive improvement withstood correction for baseline impairment, age and total years of schooling (OR 7.54, 95% CI 1.52–45.66, p = 0.018). Conclusions In addition to its established role as a biomarker in the acute phase, elevated circulating NfL levels may predict functional improvement in the late phase after stroke. Our results should prompt further studies into the use of plasma NfL as a biomarker in the late phase after stroke.

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“…Interestingly, NfL data have also been recently obtained in cerebrovascular disease forms that are occasionally associated with a rapid course, such as small vessel disease. Here, blood NfL concentrations have been associated with disability and neurological symptoms, including future cognitive impairment (Gattringer et al, 2017;Duering et al, 2018;Peters et al, 2020). Moreover, the marker correlated with disease severity, disease progression, and survival in CADASIL patients (Gravesteijn et al, 2018).…”

Section: Autoimmune Encephalitis and Other Potentially Treatable Causmentioning

confidence: 94%

Cerebrospinal Fluid and Blood Neurofilament Light Chain Protein in Prion Disease and Other Rapidly Progressive Dementias: Current State of the Art

Abu‐Rumeileh

Parchi

2021

Front. Neurosci.

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Rapidly progressive dementia (RPD) is an umbrella term referring to several conditions causing a rapid neurological deterioration associated with cognitive decline and short disease duration. They comprise Creutzfeldt–Jakob disease (CJD), the archetypal RPD, rapidly progressive variants of the most common neurodegenerative dementias (NDs), and potentially treatable conditions such as infectious or autoimmune encephalitis and cerebrovascular disease. Given the significant clinical and, sometimes, neuroradiological overlap between these different disorders, biofluid markers also contribute significantly to the differential diagnosis. Among them, the neurofilament light chain protein (NfL) has attracted growing attention in recent years as a biofluid marker of neurodegeneration due to its sensitivity to axonal damage and the reliability of its measurement in both cerebrospinal fluid (CSF) and blood. Here, we summarize current knowledge regarding biological and clinical implications of NfL evaluation in biofluids across RPDs, emphasizing CJD, and other prion diseases. In the latter, NfL demonstrated a good diagnostic and prognostic accuracy and a potential value as a marker of proximity to clinical onset in pre-symptomatic PRNP mutation carriers. Similarly, in Alzheimer’s disease and other NDs, higher NfL concentrations seem to predict a faster disease progression. While increasing evidence indicates a potential clinical value of NfL in monitoring cerebrovascular disease, the association between NfL and prediction of outcome and/or disease activity in autoimmune encephalitis and infectious diseases has only been investigated in few cohorts and deserves confirmatory studies. In the era of precision medicine and evolving therapeutic options, CSF and blood NfL might aid the diagnostic and prognostic assessment of RPDs and the stratification and management of patients according to disease progression in clinical trials.

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Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease

Cited by 34 publications

References 26 publications

Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

Plasma neurofilament light chain levels predict improvement in late phase after stroke

Cerebrospinal Fluid and Blood Neurofilament Light Chain Protein in Prion Disease and Other Rapidly Progressive Dementias: Current State of the Art

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