# Association of plasma neurofilament light protein concentration with sleep disturbance after intracerebral hemorrhage

## TL;DR

This study shows that higher levels of a brain protein in blood can predict sleep problems and recovery outcomes after a type of stroke called intracerebral hemorrhage.

## Contribution

The study demonstrates that plasma neurofilament light protein is a novel biomarker for predicting sleep disturbances and functional outcomes after intracerebral hemorrhage.

## Key findings

- Plasma neurofilament light (pNfL) levels were significantly higher in ICH patients compared to healthy controls.
- pNfL levels correlated with sleep disturbances and functional outcomes, with combined pNfL and hemorrhage volume showing better predictive accuracy.
- Elevated pNfL at admission was associated with worse prognosis and sleep issues in ICH patients.

## Abstract

Intracerebral hemorrhage (ICH) represents a critical subtype of stroke characterized by substantial morbidity and mortality. Emerging research indicates that neurofilament light protein (NfL), a biomarker indicative of neuronal damage, may offer valuable prognostic information regarding outcomes and recovery trajectories post-ICH. This study seeks to elucidate the relationship between plasma NfL (pNfL) concentrations and long-term patient outcomes, with a particular focus on sleep disturbances following ICH.

We conducted a cohort study comprising 26 healthy controls and 49 patients who had experienced ICH. The Glasgow Coma Scale (GCS) was assessed upon admission. Plasma samples were collected at admission and on 3, 7, and 14 days post-ICH. Then pNfL levels were quantified using Enzyme-Linked Immunosorbent Assay (ELISA). Clinical outcomes were evaluated at 6 months post-ICH using the Glasgow Outcome Scale-Extended (GOSE) and the Pittsburgh Sleep Quality Index (PSQI). Receiver operating characteristic (ROC) curves and the areas under the ROC curves (AUC) were utilized to determine the accuracy of hemorrhage volume and pNfL levels in identifying sleep disturbances.

pNfL levels were elevated in patients with ICH compared to healthy controls. Longitudinal analysis indicated an increasing trend in pNfL levels over the initial 7 days post-admission. pNfL levels demonstrated an AUC for distinguishing ICH patients from controls (admission for 0.92, post-ICH 3d for 0.98). In ICH patients, pNfL levels showed a positive correlation with hemorrhage volume and PSQI, and a negative correlation with GCS and GOSE. The AUCs for pNfL levels and hemorrhage volume, which were indicative of sleep disturbances, were 0.82 and 0.75, respectively. Furthermore, the combined assessment of pNfL levels and hemorrhage volume exhibited superior predictive performance compared to the evaluation of each factor individually.

pNfL represents a promising biomarker for predicting functional outcomes and evaluating sleep disturbances in patients following ICH. Elevated levels of NfL at admission are associated with poorer prognoses and increased sleep-related issues, indicating that monitoring pNfL could be valuable for prognostication and the implementation of targeted interventions.