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CURE Epilepsy’s Efforts Lead to an Increased Understanding of Epilepsy with Eyelid Myoclonia (EEM)

Key Points

  • Epilepsy with eyelid myoclonia (EEM) is a type of absence epilepsy that was formerly known as Jeavons syndrome; its main characteristic is eyelid myoclonia (a brief jerking of the eyelids that may manifest with or without absence seizures).
  • The symptoms of EEM may be confused with ocular tics and many characteristics overlap with other epilepsy syndromes, so this form of epilepsy is routinely misdiagnosed.
  • To better understand the clinical manifestations and treatment of EEM, CURE Epilepsy convened a panel of EEM expert neurologists and individuals with EEM lived experience to summarize existing knowledge, develop consensus about the diagnostic approach and clinical management of EEM and identify areas where further study is needed.
  • Several areas of consensus were identified, e.g., the use of electroencephalogram (EEG) to diagnose EEM, the recommendation for genetic testing if an individual has a family history of epilepsy, and the use of valproic acid as a first-line therapy (except in women of childbearing age) to manage EEM.

 

Deep Dive  

Epilepsy with eyelid myoclonia (EEM), formerly called Jeavons syndrome, is a generalized epilepsy syndrome (meaning that all areas of the brain are impacted by abnormal electrical activity). Onset of EEM is in childhood and affects girls more than boys. There are three main characteristics of EEM; the first and hallmark symptom of EEM is eyelid myoclonia – a brief but intense and repeated jerking of the eyelids followed by the eyeballs rolling up that may be present with or without absence seizures. The second characteristic is eye closure-induced or bright and/or flickering light-induced seizures or EEG paroxysms which are abnormal EEG patterns, and the third is photosensitivity.[1] While seizures in EEM may be as short as six seconds, they typically occur many times a day. Around one-third of people with EEM have a positive family history of epilepsy, and recently, mutations in specific genes have also been found.[1]

Although EEM was first documented in 1977,[2] the condition still is frequently underrecognized and there are delays in diagnosis.[1] EEM is a rare condition and its prevalence (the proportion of people who have EEM at a given time) in people with epilepsy is unclear but past estimates suggest it accounts for up to 2.7% of people seen at epilepsy centers.[3-5] Currently, EEM is diagnosed using routine EEG, and people with EEM have a unique EEG pattern that is characteristic of this syndrome.[6, 7] The average age of onset of EEM is 6-8 years of age [8, 9]; however, the exact time of seizure onset is difficult to establish, as eyelid jerks are routinely discounted as behavioral mannerisms.8 Indeed, the average length of time to diagnosis of EEM is reported to be delayed by as much as 9.6 years,[10] and more than 70% of patients were diagnosed with another epilepsy syndrome [10] or tics.[11] The potential for intellectual disability associated with EEM has been reported. Furthermore, issues such as irritability, anxiety, and psychosis may be seen, but knowledge about intellectual ability and psychiatric comorbidities in patients with EEM is limited.[12]

Current treatment strategies for EEM are informed by small studies; the first line of treatment consists of broad-spectrum anti-seizure medications (ASMs).[13] However, resistance to ASMs is common.[14] While for many individuals EEM persists into adulthood, it is not known whether the clinical characteristics remain the same, change, or worsen with age.

Recently, the International League Against Epilepsy (ILAE) updated the classification of epilepsy syndromes to include EEM as a generalized epilepsy syndrome of childhood with a genetic cause.[3] This, combined with the recent advances in epilepsy genetics made it an opportune time to revisit the understanding of the syndrome and develop consensus on the approach to clinical diagnosis and treatment of EEM.[13] CURE Epilepsy convened an international steering committee of EEM experts and used a modified Delphi process to survey experts around the world to develop a better understanding of the clinical presentation of EEM and establish best practices for its management.

The committee reviewed current literature and brought together a panel of 25 physicians and five individuals with lived experiences of EEM (patients and caregivers) to participate in the modified Delphi process, which consisted of three rounds of consensus-building surveys. The Delphi method is used in the medical field as a way to gather knowledge in a field, develop consensus or solve a complex problem.[15] This initiative led to three separate publications: a literature review, a summary of the clinical presentation and approach to diagnosis EEM,[13] and consensus on the treatment and management of EEM.[16]

Clinical presentation of EEM:

There was strong consensus among experts that EEM affects predominantly females and that it is a generalized epilepsy syndrome with an onset at three to 12 years of age. There was strong agreement that eyelid myoclonia must be present to make a diagnosis of EEM. The experts reiterated that eyelid myoclonia may go unnoticed for many years before a diagnosis of epilepsy is made. Absence seizures or generalized tonic-clonic seizures are seen with EEM, and EEG is critical for diagnosis. Experts recommend genetic testing when one or more of these factors is present: 1. a family history of epilepsy, 2. intellectual disability, and 3. seizures that do not respond to ASMs (drug-resistant epilepsy).[13]

All patients and caregivers mentioned stress and sleep deprivation as triggers for their seizures; they also reported that the uncontrolled eyelid myoclonia seen in EEM affects them in social and psychological settings (e.g., bullying in school). Given this, there was a strong recommendation that physicians working with people who have EEM should inquire whether their patients are experiencing psychosocial impacts.[13] Since there is not a lot known about psychosocial issues in EEM, it was recommended as an area of further investigation and research.[13]

Medical management of EEM:

In this area, there was strong consensus that valproic acid be used as the first-line treatment and that levetiracetam or lamotrigine be used as alternatives for women of childbearing age. There was strong consensus to avoid sodium channel-blocking medications (except for lamotrigine).[16] It was recognized that seizures usually continue into adulthood and that remission occurs in less than half of patients. The panel also stated that some individuals have a milder course of EEM and that they may not require ASMs at all.[16] Two manifestations of EEM emerged: one group of individuals had seizures at an earlier age, exhibited intellectual disability, and had more frequent generalized tonic-clonic seizures and/or drug-resistant epilepsy. In contrast, individuals with seizures starting at a later age and who did not have intellectual disability were likely to respond to ASM therapy.[16] For issues such as driving there was no consensus among panelists about whether patients with uncontrolled eyelid myoclonia alone should be advised not to drive, but there was a strong consensus that EEG should be used when making determinations about driving candidacy as interictal epileptiform discharges on EEG have been shown to affect driving ability.

In conclusion, the international panel convened by CURE Epilepsy identified areas of consensus regarding the clinical presentation of EEM and ways to optimally manage seizures. Areas of minimal consensus were also revealed; these include the presence of psychosocial issues, matters related to driving, and potential dietary therapies that may be beneficial in EEM. It was also discussed that there may be variability in how EEM is diagnosed worldwide, given that features of EEM are seen in other epilepsy syndromes as well.[8] These topics of further research could inform clinical trials and the development of novel therapies.

Click here to watch the recording or read the transcript for our webinar on EEM/Jeavons syndrome that took place on September 15, 2023.

 

Literature Cited:

  1. Smith KM, Wirrell EC, Andrade DM, Choi H, Trenité DK, Knupp KG, et al. A comprehensive narrative review of epilepsy with eyelid myoclonia Epilepsy Res. 2023 Jul;193:107147.
  2. Jeavons PM. Nosological problems of myoclonic epilepsies in childhood and adolescence Dev Med Child Neurol. 1977 Feb;19:3-8.
  3. Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions Epilepsia. 2022 Jun;63:1398-1442.
  4. Jonsson P, Eeg-Olofsson O. 10-year outcome of childhood epilepsy in well-functioning children and adolescents Eur J Paediatr Neurol. 2011 Jul;15:331-337.
  5. Asadi-Pooya AA, Homayoun M. Idiopathic (genetic) generalized epilepsies with absences: clinical and electrographic characteristics and seizure outcome Neurol Sci. 2020 Dec;41:3677-3682.
  6. Giannakodimos S, Panayiotopoulos CP. Eyelid myoclonia with absences in adults: a clinical and video-EEG study Epilepsia. 1996 Jan;37:36-44.
  7. Joshi CN, Patrick J. Eyelid myoclonia with absences: Routine EEG is sufficient to make a diagnosis Seizure. 2007 2007/04/01/;16:254-260.
  8. Striano S, Capovilla G, Sofia V, Romeo A, Rubboli G, Striano P, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia. 2009 May;50 Suppl 5:15-19.
  9. Reyhani A, Özkara Ç. Pitfalls in the diagnosis of Jeavons syndrome: a study of 32 cases and review of the literature Epileptic Disord. 2020 Jun 1;22:281-290.
  10. Smith KM, Youssef PE, Wirrell EC, Nickels KC, Payne ET, Britton JW, et al. Jeavons Syndrome: Clinical Features and Response to Treatment Pediatr Neurol. 2018 Sep;86:46-51.
  11. Madaan P, Jauhari P, Chakrabarty B, Gulati S. Jeavons Syndrome: An Overlooked Epilepsy Syndrome Pediatric Neurology. 2019 2019/04/01/;93:63.
  12. Nilo A, Crespel A, Genton P, Macorig G, Gigli GL, Gelisse P. Epilepsy with eyelid myoclonias (Jeavons syndrome): An electro-clinical study of 40 patients from childhood to adulthood Seizure. 2021 Apr;87:30-38.
  13. Smith KM, Wirrell EC, Andrade DM, Choi H, Trenité DK, Jones H, et al. Clinical presentation and evaluation of epilepsy with eyelid myoclonia: Results of an international expert consensus panel Epilepsia. 2023 Jun 16.
  14. Zawar I, Toribio MGG, Xu X, Alnakhli RS, Benech D, Valappil AMN, et al. Epilepsy with Eyelid myoclonias ? A diagnosis concealed in other genetic generalized epilepsies with photoparoxysmal response Epilepsy Research. 2022 2022/03/01/;181:106886.
  15. Niederberger M, Spranger J. Delphi Technique in Health Sciences: A Map Front Public Health. 2020;8:457.
  16. Smith KM, Wirrell EC, Andrade DM, Choi H, Trenité DK, Jones H, et al. Management of epilepsy with eyelid myoclonia: Results of an international expert consensus panel Epilepsia. 2023 Jun