Terminal seizure frequency and its relation to SUDEP

- Tonic-clonic seizure frequency 3 months prior to death is significantly higher in patients with probable SUDEP than controls.
- Patients with probable SUDEP suffered deterioration in seizure frequency 3 months prior to death.
- The reason for this deterioration is unclear.
- High phenobarbital dosage and drug resistance potential of patients who died from SUDEP are suspected.

BackgroundSudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with epilepsy. Several risk factors have been implicated, including early age of onset, tonic-clonic seizures and antiepileptic drugs. However, whether patients who die from SUDEP have a greater frequency of seizures in the few months before death is unclear. We investigated the terminal seizure frequency and its relation to SUDEP among a large group of patients with tonic-clonic seizures in rural West China.MethodsWe used the database from the Convulsive Epilepsy Control and Management Program in West China, which routinely provides phenobarbital (PB) as a treatment for convulsive epilepsy. Patients with probable SUDEP were included according to pre-set criteria. A verbal autopsy was undertaken for each case. By matching each patient's age, sex, date of joining the program, time in follow-up, and baseline seizure frequency, we set up a 1:5 ratio control group. SPSS 21.0 statistics were applied to compare the differences in seizure frequency 3 months prior to SUDEP between patients with probable SUDEP and controls. Furthermore, the dynamic changes of terminal seizure frequency 6-9 months, 3-6 months, and 3 months prior to SUDEP was also analyzed.ResultsA total of 41 patients who died from probable SUDEP were identified out of 7844 patients during 10 years of follow-up. The SUDEP group had a significantly higher tonic-clonic seizure frequency 3 months before their deaths than the control group (p = 0.023). At the same time, their seizure-free rate was lower than the control group (p = 0.025). Patients with probable SUDEP who were followed up over 12 months were further studied as a subgroup. They had more tonic-clonic seizures 3 months prior to death compared to the control group (p = 0.010). They also had an increase in seizure frequency in their terminal phase (3 months prior) compared to an earlier stage (3-6 months prior) (p = 0.029). Furthermore, the terminal PB dose in the SUDEP group was higher than the control group (p = 0.002).ConclusionPatients who died from SUDEP had more frequent tonic-clonic seizures 3 months before their deaths. Higher seizure frequency increases the exposure to peri-ictal pathophysiological events, which possibly relate to SUDEP. This phenomenon may be due to the drug resistance potential of these patients or the high dose of PB. Further research is required to ascertain the underlying mechanisms of SUDEP.