EEG Spikes Can Predict Impending Epilepsy in Infants With TSC

Joyce Y. Wu, MD, pediatric neurologist, UCLA Health

Joyce Y. Wu, MD

Recent study findings suggest that using 60-minute awake and asleep electroencephalography (EEG) is useful as a biomarker for ongoing epileptogenesis in the majority of infants with tuberous sclerosis complex (TSC).

The results of the study, which included 32 infants, showed that interictal epileptiform discharges (IEDs) on EEG identified incoming epilepsy in 77% of seizure-naïve infants with TSC. Additionally, persistent seizures without a history of IEDs or well‐controlled seizures correlated with low scores on the Vineland and Mullen tests at 2 years of age.

“Presence of interictal epileptiform discharges had the greatest predictive value in determining risk for developing seizures in infants with tuberous sclerosis complex TSC,” the authors, led by Joyce Y. Wu, MD, pediatric neurologist, UCLA Health, wrote. “This study demonstrates that the decline in developmental outcome in infants with TSC is clearly linked to the persistence of seizures.”

In total, 17 of 32 patients showed IEDs on their EEG studies prior to their clinical onset of seizures while 3 did not have IEDs prior to clinical onset. As well, 7 infants never developed clinical seizures and 5 had IEDs without clinical seizure onset. With this, Wu and colleagues determined a positive predictive value of 77.3% and a negative predictive value of 70 %, with a sensitivity of detecting IEDs prior to epilepsy of 85%.

The average age of IED emergence was 4.5 months (±4.0) with a median age of 4 months for those who developed seizures. Seizure onset of any type occurred at a mean of 7.5 months (±4.4) with a median of 6 months. The average interval between IED onset and clinical epilepsy onset was 3.6 months (±3.4).

In total, 20 patients experienced seizures, consisting of 35% (n = 7) focal seizures, 30% (n = 6) epileptic spasms, 5% (n = 1) focal and generalized tonic-clonic seizures, and 30% (n = 6) focal seizures with epileptic spasms.

Of the full 32-participant cohort, 37.5% (n = 12) did not have seizures during the study period with no antiepileptic drug treatment, while 21.8% (n =7) maintained normal EEG without seizures, and 15.6% (n = 5) had activity on only 1 EEG by study’s end. Prior to the onset of seizures, 6 infants were pretreated with vigabatrin, of which a single patient remained seizure-free. Of those 5 who had seizures, 3 had only focal seizures, 1 had focal seizures then epileptic spasms, and 1 had an unclassified seizure type. Two had been seizure‐free for ≥3 months by study completion, and 3 continued to have seizures. Due to this protocol deviation, Wu and co left these participants out of the developmental outcome analysis.

It is interesting to note that for the five infants who had IEDs but never developed seizures, all five had IEDs on a single EEG only, which resolved on subsequent EEG studies. This differed from the 17 infants who had persistent IEDs on serial EEG recordings before their seizure onset. Why this cortical irritability is present only transiently and culminated in seizure onset in some TSC infants but not others is not clear and deserves further attention and investigation.”

Post-seizure onset, 76% of the 20 patients were treated within 2 days, while 90% received treatment within 1 week. By the 24-month study completion date, 45% were reported to be seizure-free (for ≥3 months) while 40% continued to have seizures. A single of 3 patients (15%) who was a false negative—normal EEG with clinical seizures—was seizure-free at 24 months. The other 2 underwent epilepsy surgery after their seizure onset: 1 was reported to be seizure‐free at 24 months and 1 had a reduction in severity but continued to have occasional breakthrough seizures requiring emergency rescue medication.

“Our study demonstrates that early TSC diagnosis and serial EEG monitoring of infants can identify those TSC infants at highest risk for developing seizures months before clinical seizures will begin, but it does not clarify the role of early therapy in long‐term outcomes,” Wu and colleagues detailed. “Our clinically available EEG biomarker, through risk‐stratification, can limit vigabatrin exposure to only those at high risk for the development of epilepsy. It could be used in trials focused on preventative therapy in TSC.”

REFERENCE

Wu JY, Goyal M, Peters JM, et al. Scalp EEG spikes predict impending epilepsy in TSC infants: A longitudinal observational study. Epilepsia. Published online November 5, 2019. doi: 10.1111/epi.16379.