Spectrum of epilepsy with eyelid myoclonia: Delineation of disease subtypes from a large multicenter study

Abstract

Background: Eyelid myoclonia with absences (EMA) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission and to a less favorable neuropsychiatric outcome. However, much work is still needed to better define this generalized epilepsy syndrome. Methods:In this multicenter retrospective cohort study, we included 267 EMA patients from 9 countries. The impact of age at epilepsy onset (AEO) on EMA clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia over body regions other than eyelids (body-MYO).Results: Kernel density estimation revealed a trimodal distribution of AEO and Fisher-Jenks optimization disclosed three EMA subgroups: early-onset (EO-EMA), intermediate-onset (IO-EMA) and late-onset subgroup (LO-EMA). EO-EMA was associated with the highest rate of intellectual disability, antiseizure medication refractoriness and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO-EMA was associated with the highest proportion of body-MYO and generalized tonic-clonic seizures (GTCS), whereas IO-EMA had the lowest observed rate of additional findings. A family history of EMA was significantly more frequent in IO-EMA and LO-EMA compared with EO-EMA. In the subset of patients with body-MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in terms of other electroclinical features and seizure outcome. Conclusion:Based on AEO, we identified consistent EMA subtypes characterized by distinct electroclinical and familial features. Our observations highlight EMA as a model genetic generalized epilepsy syndrome, encompassing a spectrum of disease subtypes ranging from idiopathic generalized epilepsy to developmental/epileptic encephalopathy.

Sex‐based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia

“…15 When considering ASM treatment, we documented systematic differences in ASM exposure between females and males, showing a significantly higher use of LEV in the former group and a higher use of VPA in the latter, as observed in other GGE syndromes. 16 In the present study, prognostic factors previously identified in EEM (namely, EM status epilepticus, age at epilepsy onset, and psychiatric comorbidities) 3,4,17 could be confirmed in females only. Conversely, FS, which appeared as a strong predictor of a reduced chance of sustained remission in EEM, 2 were found to be associated with the outcome only in the male sex.…”

“…A total of 267 patients (195 females) were included in the present study. 4 Female and male EEM patients did not differ in terms of age at epilepsy onset, follow-up duration, and age at the last follow-up visit (Table 1). Female patients showed a significantly higher rate of ECS (p = .02) and PS persistence (p < .001) at the last visit, combined with a higher rate of a history of migraine (p = .047), whereas male patients showed a higher rate of ID/borderline intellectual functioning (p = .025; Table 1).…”

“…Patients were enrolled according to the following criteria, previously described elsewhere 4 : (1) EM with or without absences, (2) history of PS and/or ECS, (3) electroencephalographic (EEG) generalized spike–wave discharges (SWDs) and/or polyspike–wave discharges (PWDs), and (4) normal neuroimaging (when available). Patients with sporadic myoclonia in body regions other than the eyelids were included, provided that EM represented the predominant seizure type.…”

“…2,3 A striking female preponderance has been described along the entire EEM continuum, with a female to male ratio ranging from 2:1 to 4:1, and has been considered a disease hallmark in this heterogenous epilepsy syndrome. 4 Despite this prominent female predominance, no study has investigated the sex differences in terms of both electroclinical features and prognostic factors in EEM. Conversely, previous studies in juvenile myoclonic epilepsy (JME) highlighted relevant differences in clinical presentation according to sex, with female patients displaying higher rates of absence seizures, PS, and reflex seizures.…”

“…A striking female preponderance has been described along the entire EEM continuum, with a female to male ratio ranging from 2:1 to 4:1, and has been considered a disease hallmark in this heterogenous epilepsy syndrome 4 . Despite this prominent female predominance, no study has investigated the sex differences in terms of both electroclinical features and prognostic factors in EEM.…”