Epilepsy with Eyelid Myoclonia (EEM) / Jeavons Syndrome Initiative

With the Epilepsy with Eyelid Myoclonia (EEM) / Jeavons Syndrome Initiative, CURE Epilepsy is responding to unmet needs in an underserved epilepsy syndrome. Using our expertise, network, and resources, CURE Epilepsy has jumpstarted efforts in hopes of catalyzing further interest and investment from the community. Epilepsy with Eyelid Myoclonia (EEM) / Jeavons Syndrome Initiative phases to date have included:

• Creation of an international steering committee composed of researchers and patient advocates with expertise in EEM
  • Danielle Andrade, MD, MSc, FRCPC
  • Hyunmi Choi, MD
  • Hannah Jones, parent of child with epilepsy
  • Kelly Knupp, MD
  • Jon Mugar, parent of child with epilepsy
  • Doug Nordli, Jr., MD
  • Antonella Riva, MD
  • Kelsey M. Smith, MD
  • John M. Stern, MD
  • Pasquale Striano, MD, PhD
  • Elizabeth Anne Thiele, MD, PhD
  • Dorothée Kasteleijn-Nolst Trenité, MD, PhD, MPH
  • Elaine C. Wirrell, MD
  • Ifrah Zawar, MD
• Review of existing literature
• Use of the modified Delphi consensus process, which included three rounds of surveys to 25 physicians and 5 patients/caregivers, to develop a consensus on diagnosis and treatment
  • Consensus paper #1 (clinical presentation and evaluation)
  • Consensus paper #2 (management)

As a patient advocacy group does not exist for Jeavons syndrome, CURE Epilepsy is now undertaking basic education and awareness efforts to connect patients to research and galvanize the community.

Epilepsy with eyelid myoclonia (EEM), also known as Jeavons syndrome, accounts for approximately 1.2-2.7% of people seen at some epilepsy centers, although more research is needed. It is a generalized epilepsy syndrome with onset usually occurring between 1 to 15 years of age, with peak onset between 6 to 8 years of age. Children typically present with prominent eyelid myoclonia, which is a jerking or flickering up of the eyelids associated with the eyes rolling up, typically occurring many times in a single day. Eyelid myoclonia may be associated with absence seizures in children and eye closure sensitivity. Other seizure types may be present in people with EEM as well. Females are affected more than males at a 2:1 ratio.

A positive family history of epilepsy in many patients as well as cases in twins points to a genetic cause; however, many people with EEM do not have a genetic diagnosis. Recently, underlying genetic variants have been identified in a minority of people with EEM, including mutations in the following genes: RORB, SYNGAP1, KCNB1, NAA10, COL6A3, NEXMIF, and CHD2. Further research is needed to clarify the role of genetics in EEM, as it may influence the evolution and prognosis of the disorder as well as the search for a cure.

How Do You Identify EEM/Jeavons Syndrome and What are Treatments?

A thorough clinical history, neurological exam, and an EEG usually precede a diagnosis. If eyelid myoclonia is witnessed during a neurological exam by the diagnosing provider and other features of the diagnosis are seen on EEG, an EEG capturing eyelid myoclonia or other seizures is not required. An MRI of the brain is also not required for diagnosis, but when done is typically normal or shows changes unrelated to epilepsy.

EEM or Jeavons syndrome is a type of absence epilepsy diagnosed by the presence of the following elements:

1) Eyelid myoclonia

• Defined as a jerking, flickering or fluttering of the eyelids usually associated with upward deviation of the eye and can be associated with a tendency for the head to jerk backward.
• Required but not sufficient for an EEM diagnosis, as other epilepsies may involve eyelid myoclonia as well.
• May occur with or without visible absence seizures (loss of awareness).

2) Eye closure-induced or bright and/or flickering light-induced seizures or EEG paroxysms

• An abnormal EEG is required for diagnosis, but the absence of one does not rule out EEM, as the telltale EEG signature may not be present during all episodes.

3) Sensitivity to light

• Photosensitivity will be present at some point in life, but can go away with aging or medication use. Photosensitivity may happen in daily life and sometimes it can be captured on an EEG.

Other seizure types that may be present include:

• Generalized tonic-clonic seizures are seen in the majority of people with EEM but are usually infrequent. With these seizures, people lose control and have jerking movements of all of their extremities.
• Myoclonic seizures, which are brief jerks of the extremities.

Other reported triggers in addition to sunlight and going from darkness to light include: concentration (e.g., storytelling, recalling information, etc.), eating, lack of sleep, screen time, menstrual cycle, stress, blood sugar instability, excitement, and illness.

There is often a long delay between onset of eyelid myoclonia and recognition of it as a seizure type. Sometimes eyelid myoclonia is mistaken as an eye-blinking tic or behavioral reaction (e.g., an eye roll or “sass”); therefore, children may be taken initially to a psychologist or psychiatrist.

Sunflower syndrome was classified in 2022 as a subgroup of EEM termed “EEM with prominent photic induction” by the International League Against Epilepsy (ILAE). Individuals with Sunflower syndrome show sun-seeking behavior with hand waving in front of the eyes, which may trigger seizures, and often these patients have developmental delay. However, the relationship between EEM and Sunflower syndrome is not well-characterized and more research is needed.

Jeavons syndrome is similar to several other generalized epilepsy syndromes, which may be considered by the diagnosing doctor. Childhood absence epilepsy (CAE) is a generalized epilepsy with average onset around the same age as EEM. People with CAE typically have multiple absence seizures a day, which can be associated with eye fluttering but is not as pronounced as the eyelid myoclonia seen in EEM. CAE resolves in childhood for most people, unlike Jeavons syndrome, though there are rare reports of CAE turning into EEM.

There can also be overlap between EEM and juvenile myoclonic epilepsy (JME). The age of onset for JME is typically older, between 10-24 years. Myoclonic jerks, usually of the arms and legs, are a prominent seizure type in addition to generalized tonic-clonic seizures. Absence seizures may also be present.

Depending on clinical features, other epilepsy syndromes may be considered in the differential diagnosis including photosensitive occipital lobe epilepsy, epilepsy with myoclonic absences, Dravet syndrome, and Lennox-Gastaut syndrome.

Per the expert consensus process recently convened by CURE Epilepsy, there was a strong consensus for valproic acid as the first-line treatment for Jeavons syndrome, with levetiracetam or lamotrigine as preferable alternatives for women of childbearing age. There was a moderate consensus that ethosuximide and clobazam are also efficacious. Modern antiseizure medications like lacosamide, brivaracetam, and perampanel are also options, but more experience and research is needed. There was a strong consensus to avoid sodium channel-blocking medications, except for lamotrigine, as they may worsen seizure control. The response to different antiseizure medications can vary between patients, and trials of multiple medications may be necessary. In addition, all antiseizure medications have possible side effects that may limit their use and should be discussed with your doctor.

There is less agreement about other areas of management, including dietary therapy, blue lens therapy, and implications for driving.

• Dietary therapy: People with EEM may try diets such as the ketogenic diet, Modified Atkins diet, and low glycemic index diet. These diets are high in fat and low in carbohydrates; they require a significant amount of commitment. Individuals typically work closely with their doctor and a nutritionist for dietary therapies. Monitoring may required and side effects can be seen.
• Lens therapy: For people with Jeavons syndrome with significant photosensitivity, sometimes lens therapy can be effective at reducing seizures. Special lenses (like Ziess glasses) have been studied but are not readily available worldwide. In addition, these lenses significantly reduce light intake, and therefore, may not be well tolerated.
• Less is known about more advanced treatments for epilepsy for EEM specifically, such as a vagus nerve stimulator and responsive neurostimulation.

Intellectual ability in people with Jeavons syndrome is typically normal, but eyelid myoclonia may interfere with schoolwork and attention. Anxiety and depression may also be present, as these are common conditions seen in patients with epilepsy. Per CURE Epilepsy’s recent expert consensus process, seizures typically persist for life (with remission occurring in fewer than 50% of patients) and drug-resistant epilepsy is common.

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

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. Read more.

Educational Impacts

While cognition and development are typically normal in people with Jeavons syndrome, school difficulties and attention problems may occur. There are anecdotal reports of elevated ADHD diagnoses. There may be a need for Individualized Educations Plans (IEPs) or other learning support. Teachers may incorrectly misinterpret eyelid myoclonia as “sass” or eye-rolling or think that absence seizures are kids “just daydreaming.” Parents of children with Jeavons syndrome may also want to discuss the impact of screen time and sensitivity to light with teachers as well as healthcare providers.

Community

There is currently no 501c3 nonprofit devoted to advocacy for Jeavons syndrome. Some CURE Epilepsy community members have found a Jeavons syndrome Facebook group to be helpful and to provide a way to share experiences with others, but we cannot speak to the accuracy of information in such online communities; you should always discuss treatments with your healthcare provider.

Like many in the epilepsy community, people with Jeavons syndrome may experience stigma and discrimination. We invite you to check out our “Say the Word Say Epilepsy” campaign, that aims to combat harmful stigma and encourages people to use the word epilepsy to increase awareness and understanding in the general public.

Seizing Life Episode on EEM/Jeavons Syndrome

Other resources of interest may include:

• Rare Epilepsy Network
• NORD EEM / Jeavons syndrome page
• Epilepsy Centers
• CURE Epilepsy Webinar: Epilepsy with Eyelid Myoclonia (EEM), Formerly Known as Jeavons Syndrome: Diagnosis and Treatment of this Rare Photosensitive Epilepsy

Limited research has been conducted on Jeavons syndrome. Previously published papers before CURE Epilepsy’s Epilepsy with Eyelid Myoclonia (EEM) / Jeavons Syndrome Initiative include:

• Cerulli Irelli E, Cocchi E, Ramantani G, Caraballo RH, Giuliano L, Yilmaz T; EMA Study Group. Electroclinical Features and Long-term Seizure Outcome in Patients With Eyelid Myoclonia With Absences. Neurology. 2022 May 3;98(18):e1865-e1876. doi: 10.1212/WNL.0000000000200165. Epub 2022 Mar 15. PMID: 35292555.
• Cerulli Irelli E, Cocchi E, Ramantani G, Riva A, Caraballo RH, Morano A, et al. The spectrum of epilepsy with eyelid myoclonia: delineation of disease subtypes from a large multicenter study Epilepsia. 2022 Oct 28.
• 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 May 3.
• Striano P, Sofia V, Capovilla G, Rubboli G, Di Bonaventura C, Coppola A, et al. A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome) Epilepsia. 2008 Mar;49:425-430.
• 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 Res. 2022 Mar;181:106886.
• Zawar I, Pestana Knight EM. An Overview of the Electroencephalographic (EEG) Features of Epilepsy with Eyelid Myoclonia (Jeavons Syndrome) Neurodiagn J. 2020 Jun;60:113-127.

There are currently no clinical trials for Jeavons syndrome.

Sources

Smith KM, Wirrell EC, Andrade DM, Choi H, Trenite DK, Knupp KG, et al. A comprehensive narrative review of epilepsy with eyelid myoclonia Epilepsy Res. 2023 Apr 26;193:107147.

Smith KM, Wirrell EC, Andrade DM, Choi H, Trenite DK, Jones H, et al. Management of epilepsy with eyelid myoclonia: Results of an international expert consensus panel Epilepsia. 2023 Jun 16.

Cerulli Irelli E, Cocchi E, Ramantani G, Riva A, Caraballo RH, Morano A, et al. The spectrum of epilepsy with eyelid myoclonia: delineation of disease subtypes from a large multicenter study Epilepsia. 2022 Oct 28.

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 May 3.

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 Res. 2022 Mar;181:106886.

Zawar I, Pestana Knight EM. An Overview of the Electroencephalographic (EEG) Features of Epilepsy with Eyelid Myoclonia (Jeavons Syndrome) Neurodiagn J. 2020 Jun;60:113-127.

Striano P, Sofia V, Capovilla G, Rubboli G, Di Bonaventura C, Coppola A, et al. A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome) Epilepsia. 2008 Mar;49:425-430.