EEG and ECG in sudden unexplained death in epilepsy
Nei M, Ho RT, Abou-Khalil BW, Drislane FW, Liporace J, Romeo A and Sperling MR;
Commented by , 24 May 2004
Background
Sudden unexpected death is a major cause of mortality in people with epilepsy, most notably among those with frequent seizures. In clinical trials in refractory epilepsy, the incidence of SUDEP has been estimated at about 1:200 to 1:300 person-years (ref. 1).
SUDEP is considered to be seizure-related, but its mechanisms have not been elucidated. Cardiac rhythm disturbances associated with seizure activity are suspected to play a role.
Aim
To assess any specific EEG and ECG patterns that may predict or explain the risk of SUDEP.
Methods
Interictal and ictal ECG and EEG data were reviewed for 21 patients with definite (n=6) or probable (n=16) SUDEP who had undergone video-EEG monitoring for epilepsy. Of these, 17 had partial epilepsy, and 4 had generalized epilepsy; 15 had generalized tonic-clonic seizures (GTCS) (with or without other seizure types) and 6 had complex partial seizures (CPS) only.
Data were compared with those from 43 consecutive patients with refractory partial seizures who were alive 5 to 6 years after video-EEG monitoring. Of these, 18 had GTCS and CPS, 21 had CPS only and 3 had GTCS only.
Results
Ictal maximal heart rate (HR) was higher in SUDEP patients than in controls (149 vs. 126 bpm, p<0.001).
SUDEP patients had greater increases in HR with seizures arising from sleep than from wakefulness (78 bpm increase vs 47 bpm increase, p<0.001). A significant difference between sleep and wakefulness was not seen in controls.
The frequency of ictal cardiac repolarization or rhythm abnormalities did not differ significantly between the two groups (SUDEP 56%, controls 39%).
The site of seizure onset (laterality or lobe) showed no relation to risk of SUDEP.
Comment
Known risk factors for SUDEP include young adult age, refractory epilepsy, GTCS, mental retardation, multiple AED therapy, and low blood antiepileptic drug (AED) levels (ref. 1).
Many SUDEP victims are found in bed (ref. 2,3), suggesting that etiological factors may be enhanced by sleep.
In agreement with these factors, most SUDEP patients in this study were young, most had GTCS, all had low AED levels at the time of death (suggesting they might have been at risk for seizures), at least one third had a seizure within 8 hours of death and, for the 16 for whom information was available, 16 were asleep and 2 were awake at time of SUDEP.
Although cardiopulmonary autonomic dysfunction has been described before in people with epilepsy (ref. 4), this is the first study revealing evidence of increased seizure-related autonomic activity in patients who later died of SUDEP in comparison with a clinically similar population.
The increase in HR was particularly marked in seizures arising from sleep, an important observation given the high incidence of SUDEP during sleep. Increases in HR were also prominent during seizure clusters. One half of the patients had abnormalities in cardiac rhythm or repolarization during seizures, indicating an extreme degree of autonomic stimulation.
Possibly, seizures during sleep may cause a sudden and extreme change in autonomic tone (from predominantly vagal to extreme sympathetic), resulting in lethal cardiac arrhythmias. Some SUDEP patients had evidence of microscopic myocardial injury, suggesting that a pre-existing structural heart disease may also be a risk factor.
Although this study had limitations (limited sample size, less than perfect comparability of the two groups, possible differences in proportion of GTCS vs. CPS analysed in the two groups, possible spurious findings arising from multiple comparisons), it does point to important areas for investigation and may eventually lead to development of tools for identifying patients at special risk
The findings also have implications for prevention. Since the data strongly suggest that seizure clusters occurring during sleep in a young person may be particularly dangerous, treatment strategies aimed at suppressing nocturnal seizures and clusters could be effective in reducing the risk of SUDEP.
References
- Langan Y, Sander JWAS. Sudden unexpected death in patients with epilepsy. Definition, epidemiology and therapeutic implications. CNS Drugs 2000;13:337-49
- Leetsma JE, Walczak T, Hughes JR et al. A prospective study on sudden unexpected death in epilepsy. Ann Neurol 1989;26:195-203
- Nashef L, Walker F, Allen P, et al. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry 1996;60:297-300
- Devinsky O, Perrine K, Theodore WH. Interictal autonomic nervous system function in patients with epilepsy. Epilepsia 1994;35:199-204