Respiratory dysfunction preceding death is fundamental in sudden unexpected death in epilepsy (SUDEP) pathophysiology. Hypoxia occurs with one-third of seizures. In temporal lobe epilepsy, there is volume loss in brainstem regions involved in autonomic control and increasing neuropathological changes with duration of epilepsy suggesting increasingly impaired regulation of ventilation. In animal models, recurrent hypoxic episodes induce long-term facilitation (LTF) of ventilatory function, however, LTF is less robust in older animals. LTF of ventilation may, to some degree, ameliorate the deleterious effects of progressive brainstem atrophy. We investigated the possibility that the duration of epilepsy, or age at epilepsy onset, may impact the severity of seizure-associated respiratory dysfunction. Patients with focal epilepsy undergoing video-EEG telemetry in the epilepsy monitoring unit (EMU) were studied. We found a significant relationship between age at epilepsy onset and duration of peri-ictal oxygen desaturation for focal seizures not progressing to bilateral tonic-clonic seizures, with longer duration of peri-ictal oxygen desaturation in patients with epilepsy onset at an older age but no significant relationships between duration of epilepsy or age at EMU admission and ventilatory dysfunction. Our findings suggest an intriguing possibility that LTF of ventilation may be protective when epilepsy starts at a younger age.

Objective

The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit.

Method

We investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2 ), end-tidal CO2 (ETCO2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures.

Results

Seventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p = 0.046), ETCO2 peak change (p = 0.003) was higher, and duration of ETCO2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration.

Significance

The duration of PI and presence of PGES are associated with periictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.

Purpose

Postictal pulmonary edema (PPE) is almost invariably present in human and animal cases of sudden unexpected death in epilepsy (SUDEP) coming to autopsy. PPE may be a contributing factor in SUDEP. The incidence of postictal PPE is unknown. We retrospectively investigated PPE following generalized tonic clonic seizures (GTCS) in the epilepsy monitoring unit.

Methods

Chest X-Rays (CXR) following each GTCS were obtained in 24 consecutive patients. Relationship of CXR abnormality to seizure duration, ictal/postictal oxygen desaturation (SpO2), apnea and presence of postictal generalized EEG suppression (PGES) was investigated using logistic regression.

Results

Eleven of 24 patients had CXR abnormalities following a GTCS. In these 11 patients, 22 CXR were obtained and abnormalities were present in 15 CXR. Abnormalities included PPE in 7 patients, of which 2 also had focal infiltrates. In 4 patients focal infiltrates were present without PPE. There was no significant difference in mean time to CXR (225 min) following GTCS in the abnormal CXR group versus the normal group of patients (196 min). Mean preceding seizure duration was longer (p=0.002) in GTCS with abnormal CXR (259.7 sec) versus GTCS with normal CXR (101.2 sec). Odds-ratio for CXR abnormality was 20.46 (p=0.006) with seizure duration greater than 100 sec versus less than 100 sec. On multivariable analysis, only the seizure duration was a significant predictor of CXR abnormality (p=0.015).

Conclusions

Radiographic abnormalities are not uncommon following GTCS. The presence of CXR abnormality is significantly associated with the duration of the preceding GTCS. Severe, untreated PPE may be relevant to the pathophysiology of SUDEP.

Low-frequency (delta/theta band) hippocampal neural oscillations play prominent roles in computational models of spatial navigation, but their exact function remains unknown. Some theories propose they are primarily generated in response to sensorimotor processing, while others suggest a role in memory-related processing. We directly recorded hippocampal EEG activity in patients undergoing seizure monitoring while they explored a virtual environment containing teleporters. Critically, this manipulation allowed patients to experience movement through space in the absence of visual and self-motion cues. The prevalence and duration of low-frequency hippocampal oscillations were unchanged by this manipulation, indicating that sensorimotor processing was not required to elicit them during navigation. Furthermore, the frequency-wise pattern of oscillation prevalence during teleportation contained spatial information capable of classifying the distance teleported. These results demonstrate that movement-related sensory information is not required to drive spatially informative low-frequency hippocampal oscillations during navigation and suggest a specific function in memory-related spatial updating.