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. 2022 May 16:13:841898.
doi: 10.3389/fneur.2022.841898. eCollection 2022.

Temporal Patterning of Neurofilament Light as a Blood-Based Biomarker for Stroke: A Systematic Review and Meta-Analysis

Jasmin D Sanchez  1 , Richard A Martirosian  2 , Katherine T Mun  3 , Davis S Chong  3 , Irene Lorenzo Llorente  3 , Timo Uphaus  4 , Klaus Gröschel  4 , Teresa A Wölfer  5 , Steffen Tiedt  5 , Jason D Hinman  3 ; DEMDAS Study Group
Affiliations

Temporal Patterning of Neurofilament Light as a Blood-Based Biomarker for Stroke: A Systematic Review and Meta-Analysis

Jasmin D Sanchez et al. Front Neurol. .

Abstract

Damage to axons is a core feature of ischemic stroke and cerebrovascular disease. The burden of axonal injury is correlated with the acute clinical deficits, the underlying burden of ischemic brain injury, the prognosis of recovery, and may be a meaningful therapeutic target for brain repair. Neurofilament light chain (NfL) has been identified as a blood-based biomarker that reflects neuroaxonal damage resulting from stroke. However, the utility of NfL as a blood-based biomarker in stroke is confounded by studies examining different temporal windows and patient populations. We conducted a systematic review and meta-analysis to verify the utility of blood NfL as a diagnostic, prognostic, and monitoring stroke biomarker. Nineteen studies reporting serum/plasma NfL values for a total of 4,237 distinct patients with stroke were identified. Using available summary data from the 10 studies that employed a common immunoassay platform, we utilized random effects linear mixed modeling and weighted averages to create a phasic model of serum/plasma NfL values in distinct time periods of acute stroke. Weighted averages show that blood NfL levels vary significantly across three distinct temporal epochs of acute (0-7 days), subacute (9-90 days), and chronic (>90 days) stroke with a steep peak in the early subacute period between 14 and 21 days after stroke. Blood NfL values can function as a diagnostic biomarker in distinguishing acute ischemic stroke from transient ischemic attack as well as amongst other cerebrovascular subtypes. Release of NfL into the bloodstream after stroke follows a distinct temporal dynamic that lags several weeks behind stroke onset and reliably associates with a stroke diagnosis despite some variability based on stroke subtype and severity. Identification of these temporal dynamics and the contribution of co- existent cerebrovascular disease states can improve the value of NfL as a stroke biomarker.

Keywords: biomarker; cerebrovascular disease; meta-analysis; neurofilament (NF); stroke.

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Conflict of interest statement

JS received funding from NIA T35AG026736. TU reports grants from advanceCOR, grants from Else Kröner-Fresenius Stiftung (2018_EKMS.21), personal fees from Merck Serono, personal fees from Pfizer, outside the submitted work. KG received honoraria for advisory boards or speakers bureau for Abbott Medical, Bayer Vital GmbH, Bristol-Myers Squibb, Portola and Springer Medizin Verlag GmbH outside the submitted work. ST reports receiving funding from the Corona foundation outside of the submitted work. JH reports grants from NINDS NS115388, NS120384, and NS100608 and is an inventor on US Patent 16/487,322, and Founder of Sage Cerebrovascular Diagnostics, Inc outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram showing search and study selection process.
Figure 2
Figure 2
Temporal variance in blood NfL values by acute stroke subtypes. Weighted averages of blood NfL values (pg/mL) by TOAST stroke subtype at available intervals after stroke. Error bars indicate weighted IQR.
Figure 3
Figure 3
Temporal patterning of blood NfL values measured by SIMOA during distinct acute ischemic stroke epochs. Weighted averages of median blood NfL values (blue) at defined time points after stroke with weighted average interquartile range (pink shading) along with weighted average median blood NfL values and interquartile ranges for healthy controls, transient ischemic attack (TIA), cerebral small vessel disease (CSVD), and cerebral autosomal dominant arteriopathy with subacute infarcts and leukoencephalopathy (CADASIL) subjects.
See this image and copyright information in PMC

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