# APBA Kısa Özet
A prospective, randomized, open-label, blinded-endpoint, sham-controlled trial enrolled 35 acute ischemic stroke (AIS) patients to evaluate plasma neurofilament light chain (NfL) dynamics and the modulation of these dynamics by transauricular vagus nerve stimulation (taVNS). Patients received twice-daily taVNS or sham stimulation for five days or until discharge. NfL was measured at four time points after last known normal (LKN): Days 0 (within 24 hours), 1, 3, and 5. Plasma NfL levels continued to increase during the acute and early subacute periods following AIS. NfL trajectory modeling suggested that taVNS was associated with a less pronounced rise in NfL after AIS and with significantly lower NfL levels on Days 3 and 5 after LKN, compared with sham stimulation. Higher NfL levels predicted poorer modified Rankin Scale (mRS) scores at day 90. Factors affecting NfL levels included imaging-based measures of cerebral edema and infarct volume, race, IL-10 at admission, and thrombolytic treatment. After regressing NfL on these identified factors, treatment assignment was not significantly associated with overall NfL levels.
# Çalışma neyi araştırdı?
The primary objective was to investigate plasma NfL as a biomarker of neuroaxonal damage following acute ischemic stroke and to determine whether transauricular vagus nerve stimulation (taVNS) modulates NfL dynamics in this context. Secondary objectives included assessing the feasibility and safety of twice-daily taVNS administration and identifying clinical and imaging factors associated with NfL levels.
# Yöntem
This study was a prospective, randomized, open-label, blinded-endpoint, sham-controlled trial conducted at a single center. Thirty-five patients with acute ischemic stroke were randomized 1:1 to receive either active taVNS or sham stimulation. The taVNS protocol involved stimulation twice daily for five days or until hospital discharge. NfL levels were measured in plasma at four time points: Day 0 (within 24 hours of last known normal), Day 1, Day 3, and Day 5. In addition to NfL, researchers collected data on clinical characteristics, imaging findings (cerebral edema, infarct volume), laboratory values (including IL-10), and treatment details (thrombolytic use). The modified Rankin Scale (mRS) was assessed at 90 days to evaluate functional outcome. Statistical analysis included trajectory modeling of NfL levels and regression analysis to identify factors associated with NfL, adjusting for potential confounders.
# Temel bulgular
Plasma NfL levels continued to rise during the acute and early subacute periods following acute ischemic stroke. Trajectory modeling indicated that taVNS was associated with a less pronounced rise in NfL and significantly lower NfL levels on Days 3 and 5 after LKN compared to sham. At day 90, higher baseline or early plasma NfL levels were predictive of worse functional outcomes, as measured by the modified Rankin Scale. The identified factors influencing NfL levels were cerebral edema, infarct volume, race, IL-10 at admission, and thrombolytic treatment. Notably, after adjusting for these confounders, treatment assignment (taVNS vs. sham) was not significantly associated with overall NfL levels.
# Bulgular ne anlama geliyor?
The findings suggest that while transauricular vagus nerve stimulation (taVNS) may attenuate the rise in neurofilament light chain (NfL) during the early subacute phase after acute ischemic stroke—specifically on days 3 and 5—this modulation does not translate into a significant difference in overall NfL levels when accounting for key clinical and imaging confounders. The strong predictive value of NfL for 90-day functional outcome (mRS) underscores its potential as a prognostic biomarker. The feasibility and safety of twice-daily taVNS in this population support its use in future larger-scale studies, though the open-label design and short follow-up period necessitate cautious interpretation of the neuroprotective claims.
# Klinik önem
Higher plasma NfL levels early after acute ischemic stroke are a robust predictor of poorer functional recovery at 90 days, indicating that NfL could serve as an early prognostic tool to identify patients who may benefit from intensive rehabilitation or targeted interventions. While the trial demonstrated that twice-daily taVNS administration is feasible and safe in acute ischemic stroke, the lack of a significant independent association between taVNS and overall NfL levels after adjustment suggests that the observed day-specific reductions may be clinically meaningful but require validation in larger, blinded trials with longer follow-up to determine if they translate into improved patient-centered outcomes.
# Sınırlılıklar
The results of this trial should be interpreted within the context of several limitations. The sample size was small (n=35), which limits the generalizability of the findings and the statistical power to detect significant treatment effects. The open-label design may introduce performance and detection bias, even though the endpoint assessors were blinded. The follow-up period was short, with NfL measured only up to day 5 and functional outcome assessed at 90 days, limiting the assessment of long-term neuroprotection and delayed treatment effects. The population was limited to acute ischemic stroke patients; results may not extrapolate to other stroke subtypes (e.g., hemorrhagic stroke) or chronic phases. Additionally, no correction for multiple comparisons was mentioned, meaning that the findings on day-specific NfL differences may be exploratory in nature.