The incidence and significance of periictal apnea in epileptic seizures

Abstract

Objective: The aim of this study was to investigate periictal central apnea as a seizure semiological feature, its localizing value, and possible relationship with sudden unexpected death in epilepsy (SUDEP) pathomechanisms.

Methods: We prospectively studied polygraphic physiological responses, including inductance plethysmography, peripheral capillary oxygen saturation (SpO₂ ), electrocardiography, and video electroencephalography (VEEG) in 473 patients in a multicenter study of SUDEP. Seizures were classified according to the International League Against Epilepsy (ILAE) 2017 seizure classification based on the most prominent clinical signs during VEEG. The putative epileptogenic zone was defined based on clinical history, seizure semiology, neuroimaging, and EEG.

Results: Complete datasets were available in 126 patients in 312 seizures. Ictal central apnea (ICA) occurred exclusively in focal epilepsy (51/109 patients [47%] and 103/312 seizures [36.5%]) (P < .001). ICA was the only clinical manifestation in 16/103 (16.5%) seizures, and preceded EEG seizure onset by 8 ± 4.9 s, in 56/103 (54.3%) seizures. ICA ≥60 s was associated with severe hypoxemia (SpO₂ <75%). Focal onset impaired awareness (FOIA) motor onset with automatisms and FOA nonmotor onset semiologies were associated with ICA presence (P < .001), ICA duration (P = .002), and moderate/severe hypoxemia (P = .04). Temporal lobe epilepsy was highly associated with ICA in comparison to extratemporal epilepsy (P = .001) and frontal lobe epilepsy (P = .001). Isolated postictal central apnea was not seen; in 3/103 seizures (3%), ICA persisted into the postictal period.

Significance: ICA is a frequent, self-limiting semiological feature of focal epilepsy, often starting before surface EEG onset, and may be the only clinical manifestation of focal seizures. However, prolonged ICA (≥60 s) is associated with severe hypoxemia and may be a potential SUDEP biomarker. ICA is more frequently seen in temporal than extratemporal seizures, and in typical temporal seizure semiologies. ICA rarely persists after seizure end. ICA agnosia is typical, and thus it may remain unrecognized without polygraphic measurements that include breathing parameters.

Keywords: apnea; breathing; seizures; sudden unexpected death in epilepsy; temporal epilepsy.

Figure 1.

A left temporal lobe seizure is shown in three consecutive 30 second-pages, in polygraphic detail. In A), the patient is awake before seizure onset. Breathing movements’ cessation was noted six seconds before epileptiform discharges began. In B), during a 50 second apnea period, complete absence of breathing movement is seen, along with oxygen desaturation, with only pulse artifacts identifiable in the plethysmography signal. In C), the patient re-starts breathing 15 seconds before seizure end, when he is interviewed by nurses. The patient was apnea agnostic.

Figure 2.

Differences in polygraphy studies are represented in a typical A), generalized seizure with 3 Hz spike and wave’s discharges where no apnea is observed and B), focal epilepsy and right temporal lobe seizure where central apnea is clearly seen.

Figure 3.

Plot with error bars of ictal central apnea duration in seconds by epileptogenic zone (A) and seizure semiology (B), showing 95% confident intervals (CI) for temporal compared to extra-temporal (p<0.001) (A) and FOIA motor onset with automatisms and FOIA non-motor (dialepsis), compared to other seizure semiologies (p<0.001) (B). FOIA= focal onset impaired awareness.

Figure 4.

Peripheral capillary oxygen saturation (SpO₂) nadir and ictal central apnea (ICA) duration. The abscissa is apnea duration (in seconds) and the ordinate is the SpO₂ at apnea end. The robust simple linear regression line and 95% confidence intervals are shown. Dashed lines show that apnea duration of 60 seconds approximately correlates with SpO₂ <75%. FOA= focal onset aware, FOIA= focal onset impaired awareness, FBTCS= focal to bilateral tonic-clonic seizure, s= seconds.