Eyelid Myoclonia With Absences Research Articles

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature.

Eyelid myoclonia with absences (EMA), also known as Jeavons syndrome (JS) is a childhood onset epileptic syndrome with manifestations involving a clinical triad of absence seizures with eyelid myoclonia (EM), photosensitivity (PS), and seizures or electroencephalogram (EEG) paroxysms induced by eye closure. Although a genetic contribution to this syndrome is likely and some genetic alterations have been defined in several cases, the genes responsible for have not been identified. In this review, patients diagnosed with EMA (or EMA-like phenotype) with a genetic diagnosis are summarized. Based on this, four genes could be associated to this syndrome (SYNGAP1, KIA02022/NEXMIF, RORB, and CHD2). Moreover, although there is not enough evidence yet to consider them as candidate for EMA, three more genes present also different alterations in some patients with clinical diagnosis of the disease (SLC2A1, NAA10, and KCNB1). Therefore, a possible relationship of these genes with the disease is discussed in this review.

SYNGAP1 and Its Related Epileptic Syndromes

AbstractSynaptic Ras GTPase-activating protein 1 (SYNGAP1) is abundantly expressed in the postsynaptic space in brain tissue and has a crucial role in the regulation of the excitatory/inhibitory balance and in brain development. It is estimated that SYNGAP1 loss of function variants have an incidence of 1 to 4/10,000 individuals, mostly occurring de novo, even if few cases of vertical transmission of mosaic mutations have been reported. Loss-of-function mutations within this gene have been related with an epileptic encephalopathy characterized by eyelid myoclonia with absences (EMA) and myoclonic-atonic seizures (MAE) with early onset, commonly resistant to antiepileptic drugs (AED). Epilepsy is often associated with other clinical features, including truncal and/or facial hypotonia and/or ataxia with a wide-based and unsteady gate. Other clinical signs are intellectual disability, developmental delay, and behavioral and speech impairment, in a context of a normal neuroimaging study. In selected cases, dysmorphic features, skeletal abnormalities, and eye involvement are also described. The diagnosis of the disorder is usually established by multigene panel and, in unsolved cases, by exome sequencing. Management of the affected individuals involves different specialists and is mainly symptomatic. No clinical trials about the efficacy of AED in SYNGAP1 encephalopathy have been performed yet and Lamotrigine and valproate are commonly prescribed. In more than half of cases, however, epilepsy is refractory to AED.

Eyelid myoclonia with absences: Electroclinical features and prognostic factors.

Eyelid myoclonia with absences (EMA) is a syndrome characterized by eyelid myoclonia with or without absences, eye closure-induced generalized electroencephalographic (EEG) paroxysms and photosensitivity. Few data are available about the prognostic factors of this syndrome. The main objectives of our study were to describe the clinical and EEG features of a group of patients with EMA and to evaluate the presence of prognostic factors. We retrospectively selected a cohort of patients with diagnosis of EMA evaluated in the epilepsy service of the Neurological Clinic of Catania, in the Neurology and Clinical Neurophysiopathology Unit of Oasi Research Institute, Troina and in the Regional Epilepsy Centre of Bianchi-Melacrino-Morelli Hospital of Reggio Calabria. We considered the features of the patients during the first year of disease, and at the last follow-up visit. We stratified the patients into two groups: "seizure-free", defined as the absence of seizures for at least 2years, and "not seizure-free" and we evaluated the evolution of their characteristics and the presence of factors associated with outcome. We enrolled 51 patients (40 women (78%); mean age: 30.8years±15.5 [range 10-79]). The mean follow-up time was 8.7±5.8years. Eleven patients (21.6%) achieved the condition of seizure-free. Family history of epilepsy was associated with the condition of seizure-free (P=0.05). At the last follow-up visit, EEG photosensitivity and eye closure sensitivity were significantly associated with the condition of "not seizure-free". The results of our study revealed that a positive family history of epilepsy might be associated with a better outcome in EMA. Furthermore, the persistence of photosensitivity and eye closure sensitivity might indicate persistence of seizures, offering an aid in therapeutic management.

Prevalence and characteristics of visual aura in idiopathic generalized epilepsy

Some patients with idiopathic/genetic generalized epilepsy (IGE) experience visual aura, which can confuse the diagnosis. We sought to determine the frequency and characteristics of visual auras in IGE patients. Among the 176 IGE patients, 4 men and 7 women reported visual auras (mean age — 24years). Syndromic diagnoses were juvenile myoclonic epilepsy in four, eyelid myoclonia with absences (EMA) in three, juvenile absence epilepsy in three, and other in one. Visual auras consisted of flashing lights, macropsia, illusional movements, and blindness. Eyelid myoclonia with absences was significantly more common in the group with visual aura (3 of 11 patients vs. 8 of 165 IGE patients; P=0.02). Furthermore, photosensitivity was found significantly more common in IGE patients with visual aura (90% vs 46% of the total IGE patients) (P=0.004). In conclusion, the visual auras do not exclude a diagnosis of IGE. The presence of visual aura in the EMA syndrome is also remarkable.

Eyelid myoclonia with absences occurring during the clinical course of cryptogenic myoclonic epilepsy of early childhood

We describe a 15-year-old boy with learning difficulties and eyelid myoclonia with absences (EMA). Myoclonic jerks of the extremities and trunk occurred 9 years before the onset of EMA, when the patient was 6. At that time, we diagnosed him with cryptogenic myoclonic epilepsy of early childhood, because he manifested mainly myoclonic jerks with generalized 3- to 6-Hz spike/polyspike-and-slow-wave complexes on EEG, normal neurological examination, good response to antiepileptic drugs, and no evidence of previous brain damage. This is an unusual case showing that myoclonic epilepsy of early childhood can evolve to EMA. Although the question of whether EMA is a seizure type or an epilepsy syndrome remains controversial, our case suggests that EMA is a seizure type during the clinical course of a particular kind of myoclonic epilepsy.

Eyelid myoclonia with absences (Jeavons syndrome): A well‐defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions?

Eyelid myoclonia with absences (EMA), or Jeavons syndrome, is a generalized epileptic condition clinically characterized by eyelid myoclonia (EM) with or without absences, eye closure-induced electroencephalography (EEG) paroxysms, and photosensitivity; in addition, rare tonic-clonic seizures may also occur. Although first described in 1977 and widely reported by several authors within the last few years, EMA has not been yet recognized as a definite epileptic syndrome. However, when strict criteria are applied to the diagnosis, EMA appears to be a distinctive condition that could be considered a myoclonic epileptic syndrome, with myoclonia limited to the eyelids, rather than an epileptic syndrome with absences.

EEG‐fMRI study of the ictal and interictal epileptic activity in patients with eyelid myoclonia with absences

To investigate the blood oxygenation level-dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function. Four patients with EMA were investigated through the method of EEG-fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored. Seven sessions of EEG-fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges. The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations ("default" pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.

A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome)

Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure-induced EEG paroxysms, and photosensitivity. We conducted an open-label trial of levetiracetam in EMA. Patients were recruited in different Italian Epilepsy Centres. Levetiracetam was administrated at starting dose of 10 mg/kg/day up to 50-60 mg/kg/day in two doses. Treatment period included a 5-6 week up-titration phase and a 12-week evaluation phase. The number of days with EM (i.e., days with seizures, DwS) and number of generalized tonic-clonic seizures (GTCS) were evaluated. Analysis of intent-to-treat population was performed using Fisher's and Wilcoxon tests. Thirty-five patients (23 F) with a mean age of 19 +/- 6 years were recruited. Twenty-seven had previously undergone one to five adequate trials of antiepileptic drugs. The median number of DwS/month was 12 +/- 8.2. Twenty-one patients experienced GTCS (median number/month: 1 +/- 0.2). Thirty-four subjects completed the trial. Levetiracetam was well tolerated (mean dose: 1985 mg/day). Responders were 28/35 (80%) patients, nine taking levetiracetam as monotherapy. Six patients were seizure-free, 15 had > or =75% and seven >50% seizure reduction. GTCS remitted in 14 out of 21 (66.6%) patients. The number/month of DwS (median: 12 vs 5; p = 0.0001) and of GTCS (median: 1 vs 0; p = 0.0001) decreased compared to baseline period. Disappearance or clear reduction in paroxysmal abnormalities at eye closure occurred in 20 of the responders and photoparoxysmal response in 19. Mean follow-up was 23.9 +/- 18.5 months. Levetiracetam is effective and well tolerated in EMA. Placebo-controlled studies should confirm these findings.

Eyelid myoclonia with absences: Routine EEG is sufficient to make a diagnosis

To identify the prevalence, clinical characteristics and routine EEG features of the syndrome of eyelid myoclonia with absences (EMA) using a retrospective case control study design. EEGs from 1996 to 2005 were searched using the following keywords: eyelid flutter, eyelid blinking, tics, idiopathic generalized epilepsy, clinical absence, atypical absence and photoparoxysmal response. During the same period, patients with a diagnosis of idiopathic generalized epilepsy were identified. Patients with mainly eyelid fluttering/eyelid blinking as their seizure semiology were divided into EMA and non-EMA groups using previously published criteria and compared using parametric (Student's t-test) and non-parametric tests (Chi square) where appropriate. A p-value of <0.05 was considered significant. The keywords identified 997 patients, 288 patients were diagnosed with idiopathic generalized epilepsy; 126 had eyelid fluttering/blinking as their major seizure semiology. After excluding 51 patients due to incomplete data, of 75 remaining patients, 26 (9.03%) had EMA. Patients with EMA were (1) older at time of first EEG (OR=2.86; 95% CI=7.00-10.23; p=0.005) (2) more likely to have an event on routine EEG (OR=3.62; 95% CI=1.28-10.19; p=0.01) (3) had >3 events per day (OR=9.73; 95% CI=2.06-45.96; p=0.0012) (4) had higher prevalence of developmental delay (OR=4.46; 95% CI=1.36-14.67; p=0.01) and (5) had normal EEG background compared to the non-EMA group. EMA is not uncommon; diagnosis can be made with good clinical history and routine EEG. As developmental delay is a common association with EMA in this study, early identification and treatment are important.

Eye closure sensitivity and epileptic syndromes: A retrospective study of 26 adult cases

The transient, mainly generalized, together with brief changes in EEG baseline immediately after eye closure, is called 'eye closure sensitivity' (ECS) which was first reported by Robinson in 1930 and there have been limited number of studies investigating ECS and epilepsy syndromes. Therefore, we aimed to reveal the possible relationship between ECS and the epilepsy syndromes in our adult patients. Adult patients monitored in Hacettepe University Hospitals EEG Laboratory, from January 1995 to December 2005, were screened retrospectively for the presence of ECS. During EEG recording, all patients were asked to open their eyes for at least for 10s and close their eyes at the end of this period in six different montages. Hyperventilation and photic stimulation were performed according to the standard protocol of IPS. Twenty-six patients have had ECS during EEG recording. Nineteen (73%) were women, and mean age of the patients was 24 years. The mean ages were 12.3+/-5.4 years for seizure onset and 18.5+/-4.9 years for initial detection of ECS. Eleven had a history of febrile seizures. There was a family history for epilepsy in five patients. Photosensitivity in their EEG was noticed in 11 patients. ECS was established in five epilepsy syndromes: eyelid myoclonia with absences (EMA); (n: 6), juvenile myoclonic epilepsy (JME); (n: 6), idiopathic generalized epilepsy (IGE with tonic clonic seizure); (n: 4), juvenile absence epilepsy (JAE); (n: 1) and idiopathic occipital lobe epilepsy (IOE) (n: 9). All patients were seizure free with or without anti-epileptic medication during follow up. ECS is more common in females. It may overlap with photosensitivity but be independent from photosensitivity. It may be seen in different epilepsy syndromes including IOE which was not reported previously.

Overlap cases of eyelid myoclonia with absences and juvenile myoclonic epilepsy

Eyelid myoclonia with absences (EMA) and juvenile myoclonic epilepsy (JME) are two separate epileptic syndromes included in the new classification of epilepsies and epileptic syndromes by ILAE in 2001. Both are idiopathic generalized epilepsies with their clinical onset in the first two decades. EMA is characterized by eyelid myoclonia associated with absences and photosensitivity. Self-induced seizures are frequently seen in EMA. It can be associated with mildly mental retardation and resistance to treatment. JME includes three types of generalized seizures: typical absences, myoclonic jerks and generalized tonic-clonic seizures. The myoclonic jerks occur almost exclusively on awakening, involve preferently the upper extremities, may rarely affect the lower extremities or the entire body. More severe attacks may be accompanied by a fall. The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently restricted to the upper extremities. Generalized tonic-clonic seizures, photosensitivity and generalized polyspike-wave discharges provoked by eye closure are features of both epileptic syndromes. In this study, we describe four female patients with eyelid myoclonia associated with absences, myoclonic jerks causing falling down and rare generalized tonic-clonic seizures. All patients had good school performance and total seizure control under sodium valproate treatment. Their EEGs show generalized polyspike-wave discharges with a frequency of 3.5-6Hz always appearing a few seconds after eye closure and photoparoxysmal response. These patients show the characterictics of both epileptic syndromes. It is clinically important to make a syndromic diagnosis for an optimum advise on treatment, lifestyle restrictions and prognosis. In this study, we have gathered evidence that EMA and JME are dynamic syndromes that tend to evolve into one another.

Unusual features in eyelid myoclonia with absences: A patient with mild mental retardation and background slowing on electroencephalography

“Eyelid myoclonia with and without absences” has been incorporated into the new ILAE diagnostic scheme as a type of epileptic seizure with etiologic, therapeutic, and prognostic implications. Eyelid myoclonia with absences (EMA) is characterized by eyelid myoclonia and absences provoked mainly by eye closure and photosensivity. EMA can be a part of idiopathic, symptomatic, or probably symptomatic epileptic syndromes. EMA is the defining seizure symptom that differentiates the idiopathic reflex epileptic syndrome Jeavons syndrome from eyelid myoclonia with absences. Jeavons syndrome is characterized by unique clinical and electroencephalographic features and often genetic clustering. EMA is easily diagnosed by clinical manifestations and properly conducted electroencephalography. However, it is often misdiagnosed as tics or other types of epileptic seizures and syndromes, particularly in patients with mental retardation, behavioral disturbances, and atypical electroencephalographic findings. We describe a 19-year-old woman with EMA who remained undiagnosed for many years. She was mildly mentally retarded and her electroencephalogram showed slow background activity, which are unusual findings in Jeavons syndrome.

Video‐EEG study in an adult and a child with eyelid myoclonia with absences

Two patients with eyelid myoclonia with absences (EMA) are described. Videotape of the eyelid myoclonia in one patient is presented. An interesting feature in one patient was the induction of clinical seizures only with daylight, and in another the presence of rare, focal, epileptiform discharges during drowsiness. Valproic acid only partially controlled eyelid myoclonia in both cases. Lamotrigine, alone or in combination with valproate, can be used as an alternative but was ineffective in our cases. [Published with video sequences].

Eyelid myoclonia with absences: an overlooked epileptic syndrome?

Aim: To identify, among patients referred to our Epilepsy Center, those fulfilling eyelid myoclonia with absences (EMA) criteria and to evaluate their semiological, electroclinical and evolutive features. In addition, to examine some possible causes of underdiagnosis and to stress the role of video-EEG (VEEG) recording. Materials and methods: Retrospective analysis of 2780 epileptic patients. Inclusion criteria: Eyelid myoclonia and brief absences, related to EEG generalized paroxysmal activity and triggered by eye closure and/or by intermittent photic stimulation. Results: 7.46% of our patients with idiopathic generalized epilepsy (IGE) could be classified as EMA. Female/male ratio was 1.7:1. Familial history of epilepsy was present in about half of the patients, with two pairs of identical twins in the sample. Rare generalized tonic–clonic seizures occurred in most cases. Conclusions: EMA is a not infrequent condition among IGEs. It is likely to be underdiagnosed due to the subtle clinical semiology and to masking of EEG changes by the effects of age and anti-epileptic drugs. VEEG analysis is often needed for diagnosis of EMA. Most likely, only genetic research will be able to clarify whether EMA is a distinct epileptic syndrome.

Eye closure related spike and wave discharges: clinical and syndromic associations.

Precipitation of spike and wave (SW) discharges in some epileptic patients by eye closure (EC) has rarely been reported. To disclose the clinical characteristics and classification of syndromes of epileptic patients with SW discharges induced by EC, we investigated 10 patients (1 M, 9 F) showing this peculiar EEG feature. The patients aged between 9-39 years (mean 20.6 +/- 9.058), underwent short-term (1-3.5 hr) video-EEG investigations in order to document the appearance of the SW discharges within 3 seconds of the act of EC, in at least two occasions. Clinical analysis showed that 5 female patients who had the syndrome of juvenile myoclonic epilepsy (JME) had a later onset of epilepsy (13-15 years) than the 3 patients (3 girls) with eyelid myoclonia with absences (EMA) (3-8 years of age at onset). The remaining 2 patients who were diagnosed as childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) according to the international classification, did not show photosensitivity on the video-EEG. All but one of the 5 JME patients had experienced myoclonic seizures in intermittent photic stimulation (IPS) at the time of EC, associated with multiple spike and wave discharges. Two of the 3 EMA patients exhibited typical absences with eyelid myoclonia during the act of EC. The high rate of family history of epilepsy in first degree relatives of our patients was an outstanding feature, which could have future implications in research of the genetic basis of epilepsy patients with ECS.

Eyelid myoclonia with absences: phenomenology in children

The aim of this study is to describe the phenomenology of children with eyelid myoclonia with absences (EMA) in relation to EEG findings and diagnosis, with particular reference to the issue of self-induction. Case notes of all children with a diagnosis of EMA within a regional paediatric neurology clinic were identified. Each child was interviewed by a paediatric neurologist with or without a child psychiatrist and their EEG reviewed by a clinical neurophysiologist. Six patients (five female, one male) were identified. Clinical and EEG features and treatment responses were in keeping with the established literature. Five of the six patients demonstrated various compulsive or tic-like symptoms including premonitory sensations, compulsive, difficult to resist urges and a sense of relief associated with the absence attacks. Separate facial tics not associated with absences were also evident in at least two children. The argument that self-induction does not occur in EMA assumes its deliberate nature, which may not necessarily be the case for a proportion of these children. Compulsive 'self-induction' may be similar to the phenomenology described in Tourette's syndrome (TS) where individuals experience motor and vocal tics and obsessive compulsive symptoms. The relationship between this argument and EEG findings in EMA would presume that the initial eye ball roll/eye closure and eye blinking (tics seen in TS) are tic-like symptoms which cause the absences and discharges of EMA in those who are photosensitive. In this model the self-induction of discharges in an individual may or may not be deliberate, or even go unnoticed by the patient. The beneficial response of some so-called 'self-inducers' to the proconvulsive dopamine antagonists (commonly prescribed for TS) lends further support to this argument.

EYELID MYOCLONIA WITH ABSENCES. 1996. Edited by John S Duncan, CP Panayiotopoulos. Published by John Libbey & Company Limited. 122 pages. $C43.00 approx.

EYELID MYOCLONIA WITH ABSENCES. 1996. Edited by John S Duncan, CP Panayiotopoulos. Published by John Libbey & Company Limited. 122 pages. $C43.00 approx.

Eyelid myoclonia with absences in adults: a clinical and video-EEG study.

We report clinical and video-EEG findings in 11 adults with the syndro me of eyelid myoclonia with absences (EMA). Prevalence was 2.7% among all epilepsies and 12.9% among idiopathic generalized epilepsies (IGE) with typical absences. All patients with EMA were women, with a mean age of 30.9 years and a mean age of 7.8 years at reported onset of eyelid myoclonia. The characteristic seizures, studied with video-EEG in 10 patients, began with and were mainly manifested by eyelid myoclonia, either alone if brief (< or = 2 s) or with associated mild impairment of consciousness if longer. The ictal EEG was characterized by polyspike and slow waves at 3-6 Hz. Ictal clinical and EEG manifestations occurred mainly after eye closure and were inhibited by total darkness. All patients were photosensitive, but photosensitivity decreased with age; nonpatient had self-induced seizures. Infrequent generalized tonic-clonic seizures (GTCS) occurred in all but the youngest patient; they were usually infrequent and were precipitated mainly by flickering lights, sleep deprivation, fatigue, and menstruation. Mild myoclonic jerks of the upper limbs occurred in 6 patients. Eyelid myoclonia was resistant to medication and persisted despite control of other seizures.

Transport and metabolism of glutamic acid studied in the human placenta by an in vitro perfusion method

Eyelid myoclonia with absences (EMA) and juvenile myoclonic epilepsy (JME) are two separate epileptic syndromes included in the new classification of epilepsies and epileptic syndromes by ILAE in 2001. Both are idiopathic generalized epilepsies with their clinical onset in the first two decades. EMA is characterized by eyelid myoclonia associated with absences and photosensitivity. Self-induced seizures are frequently seen in EMA. It can be associated with mildly mental retardation and resistance to treatment. JME includes three types of generalized seizures: typical absences, myoclonic jerks and generalized tonic-clonic seizures. The myoclonic jerks occur almost exclusively on awakening, involve preferently the upper extremities, may rarely affect the lower extremities or the entire body. More severe attacks may be accompanied by a fall. The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently restricted to the upper extremities. Generalized tonic-clonic seizures, photosensitivity and generalized polyspike-wave discharges provoked by eye closure are features of both epileptic syndromes. In this study, we describe four female patients with eyelid myoclonia associated with absences, myoclonic jerks causing falling down and rare generalized tonic-clonic seizures. All patients had good school performance and total seizure control under sodium valproate treatment. Their EEGs show generalized polyspike-wave discharges with a frequency of 3.5–6 Hz always appearing a few seconds after eye closure and photoparoxysmal response. These patients show the characterictics of both epileptic syndromes. It is clinically important to make a syndromic diagnosis for an optimum advise on treatment, lifestyle restrictions and prognosis. In this study, we have gathered evidence that EMA and JME are dynamic syndromes that tend to evolve into one another.

Eyelid Myoclonia with Absences (EMA) in Two Monovular Twins

EMA (eyelid myoclonia with absences) consists of brief seizures triggered by eyelid closure and characterized by absence and palpebral myoclonia. The EEG shows brief discharges with 3 per second spike and wave complexes. The present report describes the cases of 2 monovular twins who started to have this form of epilepsy at the age of 4 1/2 years. Their seizures, after 2 years of follow-up, are greatly reduced with combined therapy of valproic acid and benzodiazepines (Clobazam).