Sudden death in epilepsy: An experimental animal model

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Mameli O, Caria MA, Pintus A, Padua G, and Mameli S (2006) Sudden death in epilepsy: An experimental animal model. Seizure 15:5 275–87.

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Abstract: INTRODUCTION: The physiopathogenetic mechanisms possibly involved in sudden unexplained epileptic death (SUDEP), were investigated in the hemispherectomized rat. METHODS: For this purpose, paroxysmal activity, vagal nerve firing, systemic blood pressure (BP), pulmonary artery pressure, and ECG were simultaneously recorded in an experimental animal model of epilepsy. Recordings were performed in basal conditions and during paroxysmal activity induced by topical application of penicillin-G at hypothalamic and mesencephalic level. During the experiment were also performed hemogas analysis and at end, samples of lung tissue were processed for histology. RESULTS: Activation of hypothalamic (HEF) and mesencephalic (MEF) epileptic foci induced a significant increase of spontaneous vagal nerve firing that was strictly correlated to ECG impairments and hypotension. When paroxysmal activity extinguished, vagal nerve activity and cardiovascular parameters returned to basal conditions. However, in 25% of the animals, co-activation of HEF and MEF always triggered a vagal hypertone which was temporally correlated to cardiac arrhythmias, but also to hyperkalemia, acidosis, pulmonary hypertension and to animal death. Histological control in lungs of deceased animals showed an alveolar and perivessel oedema with an oedematous infiltration in the alveolar and bronchial spaces and mucous secretion. During ictal activity, comparison between survived and deceased animals showed significant differences in the incidence of ECG impairment of pulmonary artery pressures, pO2, and pCO2 pressures, and [K+], [HCO3-], and [pH], concentrations. DISCUSSION: A possible explanation of the above observations is discussed in relationship to SUDEP physiopathogenesis.

Keywords: Sudden epileptic death; Cardioarrhythmogenic cerebral triggers; Parasympathetic activity; Cardiovascular parameters; Lung histology; Hemogas parameters


  • In rats, application of penicillin-G locally to hypothalamic or mesencephalic regions caused increased spontaneous vagal nerve firing that correlated with bradycardia and hypotension. This generally resolved spontaneously, but in a subset of animals seizures due to joint activation of both regions led to increased vagal tone and bradycardia, hyperkalemia, pulmonary hypertension, and death. Though this is suggestive of SUDEP, one difference is the considerable time required for the severe pathologic entity to evolve (60 minutes or more). The study shows an interesting link between field potential recordings near the thalamus and EKG abnormalities. The analyses of blood gas and metabolic parameters are noteworthy for their detail and comprehensiveness, but most of the measurements seem merely to reflect the death of the animal rather than any particular pathophysiologic mechanism. The increase in potassium seems more easily explained by the acidosis due to hypoxia after cardiopulmonary dysfunction rather than as a direct result of vagal activation. However, the correlation of potassium level and number of vagal nerve spikes may suggest a more direct mechanistic link (though in the discussion the elevated potassium is linked to elevated sympathetic, rather than parasympathetic, activation).