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Investigating cardiorespiratory fitness, cerebral blood flow, and brain metabolism in epilepsy

Year: 2026

Type: article

Abstract: Introduction: Idiopathic generalized epilepsies (IGEs) are characterized by seizures that propagate through widespread thalamocortical networks including the anterior cingulate cortex (ACC). Poor cardiorespiratory fitness may exacerbate neurovascular and metabolic vulnerability including heightened susceptibility to sudden unexpected death in epilepsy. We aimed to examine cardiorespiratory fitness, regional cerebral blood flow (CBF), and metabolite concentrations in patients with IGEs (PwIGEs) and to determine the effect of seizure control status on these physiological and neurochemical measures. Methods: Forty-six participants (31 PwIGEs, 15 healthy controls) underwent a graded exercise test to assess maximal oxygen uptake (VO2peak) as a measure of cardiorespiratory fitness and completed 3T MRI including multi-delayed pseudo-continuous arterial spin labeling (pCASL) to assess CBF and single-voxel spectroscopy (SVS) to assess ratios of N-acetylaspartate and glutamate/glutamine complex to total creatine (NAA/tCr and Glx/tCr, respectively) in the ACC and thalamus. Group differences and seizure control effects in PwIGEs were examined using analysis of covariance (ANCOVA). Results: VO2peak, thalamic CBF, ACC NAA/tCr, and ACC Glx/tCr did not significantly differ between groups. PwIGEs exhibited higher ACC CBF (p = 0.039) and lower thalamic NAA/tCr (p = 0.012) than healthy controls. PwIGEs with active seizures showed significantly lower thalamic Glx/tCr compared to those who were seizure-free (p = 0.003). Discussion: These findings suggest poor cardiorespiratory fitness is not epilepsy-specific and likely attributable to lifestyle and that region-specific alterations in perfusion and metabolic milieu in PwIGEs characterized by higher ACC CBF and lower thalamic NAA/tCr and Glx/tCr in those with active seizures. The multimodal neuroimaging approach provides convergent evidence of thalamocortical network dysregulation underlying IGE pathophysiology.

Source: Frontiers in Network Physiology

DOI: 10.3389/fnetp.2026.1894335