Postictal Generalized EEG Supression Postictal Generalized EEG Suppression or PGES was originally described by Lhatoo. You can see GTCS, after seizure, EEG shows generalized suppression. This is PGES. Poh MZ, 2012, Neurology

10 vEEG of PWE who later died of SUDEP PGES 50% of seizures in patients who later died of SUDEP PGES >50 seconds in duration associated with an increased risk of SUDEP >50 seconds OR 5.22 >90 seconds OR 23.46 We studied 10 adult patients from our video-telemetry database who had 30 documented epileptic seizures during video-EEG recording and who later died of SUDEP. They were compared with 30 matching live controls with 92 epileptic seizures taken from the same database. Clinical and EEG findings were analyzed. RESULTS: PGES was seen in 15/30 (50%) case and 35/92 (38%) control seizures. A Mann-Whitney U test showed that PGES was significantly longer in the generalized motor seizures of the SUDEP group (p < 0.001). After adjustment for variables, odds ratio analysis of all seizures indicated significantly elevated odds of SUDEP with PGES durations of >50 seconds (p < 0.05). Beyond 80 seconds, the odds were quadrupled (p < 0.005). After adjustment for variables, for each 1-second increase in duration of PGES, the odds of SUDEP increased by a factor of 1.7% (p < 0.005). INTERPRETATION: Prolonged PGES (>50 seconds) appears to identify refractory epilepsy patients who are at risk of SUDEP. Risk of SUDEP may be increased in direct proportion to duration of PGES. Profound postictal cerebral dysfunction, possibly leading to central apnea, may be a pathogenetic mechanism for SUDEP.

SUDEP in the EMU 16 cases occurred in EMUs reported in literature 5 near SUDEP 11/11 SUDEP and 5/6 Near SUDEP occurred after GTC seizure, 1 after CPS Postictal respiratory & cardiac dysfunction Postictal tachypnea Postictal bradycardia Followed within 3 minutes by transient or terminal apnea and bradycardia First, the immediate postictal phase was characterised by rapid breathing between 18 and 50 breaths per min (median 30 per min, IQR 21–30), while heart rate varied from 55 to 145 beats per min (median 90 per min, IQR 76–101). Second, postictal generalised EEG suppression was observed in all monitored SUDEP cases once EEG was no longer obscured by respiratory-related artifacts. Third, an early cardio respiratory dysfunction developed in all patients during the first 3 min postictally This dysfunction was characterised by bradycardia (<45 beats per min) starting between 15 and 140 s postictally (median 100 s, IQR 48–130) and culminating in asystole in nine patients (90%) between 20 and 190 s postictally (median 135 s, IQR 106–146; fi gure 3), periods of apnoea with onset varying between 25 and 180 s postictally (median 118 s, IQR 61–136; fi gure 3), and a parallel worsening of cardiac and respiratory dysfunction that usually peaked together between the fi rst and third minutes postictally (appendix). Fourth, terminal apnoea always preceded terminal asystole (fi gure 2). Ryvlin et al Lancet Neurol 2013

Cardiorespiratory abnormalities within 3 minutes post ictal Terminal apnea always precedes asystole Ryvlin et al Lancet Neurol 2013

Case control study of PGES in SUDEP patients and controls 122 seizures in 57 patients 15% of seizures were associated with PGES in 26% of patients PGES was associated significantly with secondarily generalized seizures BUT, frequency and duration of PGES were not more common in SUDEP group Epilepsy & Behav, 2011

PGES is common following GTC Following 16-90% of GTC in adult studies 32% of children admitted for vEEG Sickkids cohort 6.5% of 399 ictal vEEG at SickKids 54% of 41 children with GTC Mosely, 2013; Okanari, in preparation

PGES is associated with GTC with all limb tonic posturing ALTP + PGES + PGES ― ALTP - * ●●We focused on all limb tonic-extension posture, you can see in GTCS. We analyzed all 76 GTCS with or without PGES. ●26 GTCS have all limb tonic extension posture with PGES. There was as significantly high occurrence of PGES in GTCS with all limbs tonic-extension posture. *p<0.001

PGES duration and seizure type This slide shows the correlation between duration of PGES and Seizure type. ●●●The duration of PGES in 42 seizures with GTCS was significantly longer than ●the duration of PGES in 6 seizures without GTCS. ●The duration of PGES was not significantly different for seizures that were partial with secondary generalization and GTCS alone. (GTCS: GTCS without focal signs) 2GTCS 37 GTCS 5 GTS 5 GCS 1 * p < 0.005

Duration of PGES & Age R = 0.74, p < 0.001 This slide shows correlation duration of PGES and Age. The age of 26 patients with PGES ranged from 26 days to 17 years. The older children presented the significantly longer duration of PGES. R = 0.74, p < 0.001

EEG background & duration of PGES Sleep spindle REM sleep 14 11 19 18 6 * ** We analyzed the correlation between PGES and EEG background features including: awake background activity, sleep spindle, and REM sleep. We defined disorganized EEG findings as no posterior dominant rhythm, no reactivity and slow for age of awake background activity, low incidence or absence of sleep spindles and REM sleep. Duration of PGES was significantly longer in children with ●●normal awake background, ●●normal sleep spindles and ●●●normal REM sleep than that in disorganized awake background, disorganized sleep spindles and disorganized REM sleep. 7 Awake Normal Disorganized *p<0.005, **p<0.001

Conclusions PGES is relatively common and may be predicted based on seizure characteristics. Prolonged PGES may be a biomarker for SUDEP risk. PGES in association with other stressors, environmental factors, other dynamics may be a more powerful biomarker. More human and experimental data is needed. The best way to reduce SUDEP risk is to reduce the frequency of convulsive seizures.

Education is the most accessible tool we have to reduce the burden of mortality in epilepsy. #iamsudepaware

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