Evaluation of Neurovascular Coupling in Early‐Onset and Late‐Onset Epilepsy of Unknown Etiology

BACKGROUND: Previous studies have shown neurovascular coupling (NVC) dysfunction in epilepsy, suggesting its role in the pathological mechanisms. However, it remains unclear whether NVC abnormalities exist in epilepsy of unknown etiology (EU). PURPOSE: To integrate multiparametric MRI to assess NVC and its relationship with cognition in early-onset and late-onset EU patients. STUDY TYPE: Prospective. POPULATION: Ninety-six EU patients (46 early-onset, M/F = 20/26; 50 late-onset, M/F = 29/21) and 60 healthy controls (HCs, M/F = 25/35). FIELD STRENGTH/SEQUENCE: 3.0 T, resting-state gradient echo-planar imaging, pseudo-continuous arterial spin labeling (pc-ASL), and T1-weighted brain volume sequence. ASSESSMENT: Functional MRI data were analyzed to assess intrinsic brain activity including amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS), while pc-ASL provided cerebral blood flow (CBF) measurements. Coupling correlation coefficients and ratios of CBF to neural activity were calculated to evaluate global and regional NVC. STATISTICAL TESTS: Two-sample t-test, Analysis of Variance, Kruskal-Wallis test, Chi-square test, Analysis of Covariance, family-wise error/Bonferroni correction, partial correlation analyses. Statistical significance was defined as P < 0.05. RESULTS: Whole-brain analysis revealed increased ALFF values in both patient groups' left precentral and postcentral gyri. Both patient groups had lower global NVC coefficients than HCs, with reduced CBF-ALFF (0.28 vs. 0.30), CBF-fALFF (0.43 vs. 0.45), and CBF-ReHo (0.40 vs. 0.41) in early-onset patients, and lower CBF-fALFF (0.38 vs. 0.45) and CBF-ReHo (0.32 vs. 0.41) in late-onset patients. Regional analysis showed significantly decreased CBF/ALFF ratios in the left precentral and postcentral gyri (T = 3.85 to 5.33). Reduced global NVC in early-onset patients was significantly associated with poorer executive function (r = 0.323), while global coupling in late-onset patients was negatively correlated with disease duration (r = -0.348 to -0.426). DATA CONCLUSION: This study showed abnormal global and regional NVC in both early-onset and late-onset EU patients, emphasizing the potential role of NVC in the pathophysiological mechanisms of EU. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.