Generalized Fast Discharges Along the Genetic Generalized Epilepsy Spectrum: Clinical and Prognostic Significance

Abstract

ObjectiveTo investigate the electroclinical characteristics and the prognostic impact of generalized fast discharges in a large cohort of genetic generalized epilepsy (GGE) patients studied with 24-h prolonged ambulatory electroencephalography (paEEG).MethodsThis retrospective multicenter cohort study included 202 GGE patients. The occurrence of generalized paroxysmal fast activity (GPFA) and generalized polyspike train (GPT) was reviewed. GGE patients were classified as having idiopathic generalized epilepsy (IGE) or another GGE syndrome (namely perioral myoclonia with absences, eyelid myoclonia with absences, epilepsy with myoclonic absences, generalized epilepsy with febrile seizures plus, or GGE without a specific epilepsy syndrome) according to recent classification proposals.ResultsGPFA/GPT was found in overall 25 (12.4%) patients, though it was significantly less frequent in IGE compared with other GGE syndromes (9.3 vs. 25%, p = 0.007). GPFA/GPT was found independently of seizure type experienced during history, the presence of mild intellectual disability/borderline intellectual functioning, or EEG features. At multivariable analysis, GPFA/GPT was significantly associated with drug resistance (p = 0.04) and with a higher number of antiseizure medications (ASMs) at the time of paEEG (p < 0.001) and at the last medical observation (p < 0.001). Similarly, GPFA/GPT, frequent/abundant generalized spike-wave discharges during sleep, and a higher number of seizure types during history were the only factors independently associated with a lower chance of achieving 2-year seizure remission at the last medical observation. Additionally, a greater number of GPFA/GPT discharges significantly discriminated between patients who achieved 2-year seizure remission at the last medical observation and those who did not (area under the curve = 0.77, 95% confidence interval 0.57–0.97, p = 0.02)ConclusionWe found that generalized fast discharges were more common than expected in GGE patients when considering the entire GGE spectrum. In addition, our study highlighted that GPFA/GPT could be found along the entire GGE continuum, though their occurrence was more common in less benign GGE syndromes. Finally, we confirmed that GPFA/GPT was associated with difficult-to-treat GGE, as evidenced by the multivariable analysis and the higher ASM load during history.

Drug resistance in idiopathic generalized epilepsies: Evidence and concepts

“…Three studies confirmed the prognostic value of generalized polyspike trains (GPTs)—a feature usually associated with LGS, which was first described by Sun et al in a cohort of patients referred for long‐term EEG monitoring, and confirmed by Cerulli Irelli et al and Kamitaki et al 41 , 42 , 43 Conrad et al complemented these studies by showing that GPTs were twice as often found in sleep than in wake EEGs, stressing the need for prolonged EEG recordings (>24 h) to capture GPTs, which is in keeping with findings by Jensen et al, showing that GPTs are rare on routine EEGs. 44 …”

“…Generalized paroxysmal fast activity (GPFA) is traditionally linked to LGS but is seen in 5.6%–18.9% of patients with otherwise typical IGE with absence seizures 46,47 . In several large independent cohorts, GPFA has been linked to persistent seizures and drug resistance in both children and adults 42,47 …”

“… 46 , 47 In several large independent cohorts, GPFA has been linked to persistent seizures and drug resistance in both children and adults. 42 , 47 …”

BIRDs (Brief Potentially Ictal Rhythmic Discharges) watching during EEG monitoring

“…GPFA was historically considered a marker for Lennox-Gastaut syndrome or other epileptic encephalopathies ( 19 – 21 ). More recently, this was recognized in patients with normal cognition and generalized epilepsy ( 22 – 25 ). Most recent studies have described the association between the presence of GPFA and drug resistance and no specific association with a particular type of generalized epilepsy ( 25 , 26 ).…”

“…More recently, this was recognized in patients with normal cognition and generalized epilepsy ( 22 – 25 ). Most recent studies have described the association between the presence of GPFA and drug resistance and no specific association with a particular type of generalized epilepsy ( 25 , 26 ). Focal PFA has also been described in patients with focal epilepsy, and their relationship to seizure onset zone and intractability has been suggested ( 27 – 29 ).…”