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Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke.

ABSTRACT: Serum neurofilament light chain protein (sNfL) shows promise as a biomarker for infarct size in acute ischemic stroke and for monitoring cerebral small vessel disease (cSVD). However, distinguishing the cSVD contribution after stroke may not be possible due to post-stroke sNfL increase. Additionally, it remains unclear if etiologic subtype differences exist. We measured infarct and white matter hyperintensity (WMH) volumes using MRI at the index stroke in ischemic stroke patients (n = 316, mean age 53 years, 65% males) and at 7-year follow-up (n = 187). Serum NfL concentration was measured in the acute phase (n = 235), at 3-months (n = 288), and 7-years (n = 190) post stroke. In multivariable regression, acute and 3-month sNfL concentrations were associated with infarct volume and time since stroke, but not with stroke etiology or infarct location. Seven years post-stroke, sNfL was associated with WMHs and age, but not with stroke etiology. Nonlinear regression estimated that sNfL peaks around 1 month, and declines by 50% at 3 months, and 99% at 9 months. We conclude that sNfL can indicate infarct volume and time since brain injury in the acute and subacute phases after stroke. Due to the significant post-stroke sNfL increase, several months are needed for reliable assessment of cSVD activity.

SUBMITTER: Holmegaard L

PROVIDER: S-EPMC11246414 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke.

Holmegaard Lukas L Jensen Christer C Pedersen Annie A Blomstrand Christian C Blennow Kaj K Zetterberg Henrik H Jood Katarina K Jern Christina C

Scientific reports 20240713 1

Serum neurofilament light chain protein (sNfL) shows promise as a biomarker for infarct size in acute ischemic stroke and for monitoring cerebral small vessel disease (cSVD). However, distinguishing the cSVD contribution after stroke may not be possible due to post-stroke sNfL increase. Additionally, it remains unclear if etiologic subtype differences exist. We measured infarct and white matter hyperintensity (WMH) volumes using MRI at the index stroke in ischemic stroke patients (n = 316, mean ...[more]

PMID: 39003344

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Project description:ImportanceAlthough increasing evidence suggests that trimethylamine N-oxide (TMAO) is associated with atherosclerosis, little is known about whether TMAO and its related metabolites (ie, choline, betaine, and carnitine) are associated with small vessel disease.ObjectiveTo evaluate the association between TMAO and its related metabolites with features of cerebral small vessel disease, including white matter hyperintensity volume (WMHV) and acute lacunar infarction.Design, setting, and participantsThis cross-sectional study included patients enrolled in the Specialized Programs of Translational Research in Acute Stroke biorepository. The registry included 522 patients with acute ischemic stroke who were 18 years or older who presented at the Massachusetts General Hospital or Brigham and Women's Hospital within 9 hours after onset between January 2007 and April 2010. The analyses in this study were conducted between November 2022 and April 2023.ExposuresPlasma TMAO, choline, betaine, and carnitine were measured by liquid chromatography-tandem mass spectrometry.Main outcomes and measuresWMHV was quantified by a semiautomated approach using signal intensity threshold with subsequent manual editing. Ischemic stroke subtype was classified using the Causative Classification System.ResultsAmong 351 patients included in this study, the mean (SD) age was 69 (15) years; 209 patients (59.5%) were male and had a median (IQR) admission National Institute of Health Stroke Scale of 6 (3-13). The magnetic resonance imaging subgroup consisted of 291 patients with a mean (SD) age of 67 (15) years. Among these, the median (IQR) WMHV was 3.2 (1.31-8.4) cm3. TMAO was associated with WMHV after adjustment for age and sex (β, 0.15; 95% CI, 0.01-0.29; P < .001). TMAO remained significant in a multivariate analysis adjusted for age, sex, hypertension, diabetes, and smoking (β, 0.14; 95% CI, 0-0.29; P = .05). TMAO was associated with lacunar stroke but not other ischemic stroke subtypes in a model adjusted for age, sex, hypertension, diabetes, and smoking (OR, 1.67; 95% CI, 1.05-2.66; P = .03).Conclusions and relevanceIn this observational study, TMAO was associated with cerebral small vessel disease determined by WMHV and acute lacunar infarction. The association was independent of traditional vascular risk factors.

Dataset Information

Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke.

Publications

Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke.

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