Work

Seizure‐type–specific disruption of hypercapnic cardioventilatory responses in epilepsy models

Year: 2026

Type: article

Abstract: Objective Sudden unexpected death in epilepsy (SUDEP) is linked to respiratory and autonomic failure with post‐ictal periods of prolonged hypercapnia indicative of impaired central chemoreception. Yet how interictal hypercapnic cardioventilatory responses vary by seizure phenotype is unclear. We aimed to determine whether central chemoreception and autonomic regulation differ across epilepsy phenotypes during a standardized CO 2 challenge. We hypothesized that rats with chronic generalized tonic–clonic seizures would show impaired hypercapnic cardioventilatory and autonomic responses compared with rats with generalized absence seizures and healthy controls. Methods We measured breathing frequency (f B ), heart rate (HR), and heart rate variability (HRV) before, during, and after a 1 h 10% CO 2 exposure in three groups of male rats: kainic acid (KA; tonic–clonic), genetic absence epilepsy rat from Strasbourg (GAERS; absence), and Wistar controls. Results Controls showed increased f B and decreased HR during hypercapnia. KA rats exhibited blunted f B and HR responses; GAERS displayed preserved f B elevation with faster post‐challenge normalization and intermediate HR changes. Coupling of f B and HR collapsed during CO 2 in both epilepsy groups and re‐emerged in recovery. In KA rats, Stage 3–4 seizure burden positively correlated with HR during hypercapnia. HRV reactivity to hypercapnia was robust in controls, attenuated in GAERS, and largely absent in KA, whereas interictal baseline HRV did not differ among the groups. Significance These data support seizure‐type–specific disruption of chemoreflex–autonomic integration. Extending clinical hypercapnic ventilatory response (HCVR) testing, a hypercapnic cardioventilatory response (HCCVR), that is, a combined f B , HR, and HRV readout, may help to refine SUDEP risk stratification beyond seizure frequency and type.

Source: Epilepsia

DOI: 10.1002/epi.70123