Myoclonic Absences Research Articles

Video/EEG recording of myoclonic absences in GLUT1 deficiency syndrome with a hot-spot R126C mutation in the SLC2A1 gene

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is an inborn error of brain energy metabolism characterized by impaired glucose transport into the brain. A classic phenotype comprising epilepsy, mental retardation, an often paroxysmal disorder, and several subtypes has been described. Although typical absences are frequent in GLUT1DS, myoclonic absence seizures are rarely reported. Here we describe a novel Turkish patient with a hot-spot mutation (R126C) in the SLC2A1 gene who presented with unusual myoclonic absence epilepsy and paroxysmal shivering. The case is discussed in view of eight other cases carrying the R126C mutation.

P14.5 Favourable response of epilepsy with myoclonic absences to rufinamide

P14.5 Favourable response of epilepsy with myoclonic absences to rufinamide

Rufinamide. A new therapeutic option for epilepsy with myoclonic absences

Rufinamide. A new therapeutic option for epilepsy with myoclonic absences

Epilepsy with Myoclonic Absences – Favourable Response to Add-on Rufinamide Treatment in 3 Cases

Epilepsy with myoclonic absences (EMA) is a rare epileptic syndrome with frequently poor response to antiepileptic treatment. Rufinamide (RUF) is a relatively new EMEA- and FDA-approved anticonvulsant licensed as an orphan drug for the adjunctive treatment of patients with Lennox-Gastaut syndrome. A retrospective data analysis in 3 patients was performed. Add-on RUF treatment was initiated in 3 boys with EMA refractory to conventional antiepileptic therapy (primidone + valproic acid, n=1; levetiracetame + ethosuximide, n=2). It resulted in complete cessation of all seizures in 2, and a 50% reduction of the seizure frequency in one child, respectively. RUF add-on therapy should be considered in children with EMA not responding to conventional antiepileptic therapy.

Absence seizures in the first 3 years of life: An electroclinical study of 46 cases

Early onset absence seizures have been considered a rare heterogeneous group with a poor prognosis. Only few patients may be categorized into well-known syndromes. We have evaluated electroclinical features, evolution, and the nosologic boundaries of early onset absence seizures. Forty-six neurologically normal patients with absence seizures associated with bilateral, synchronic, or asynchronic, and symmetric or asymmetric spike-and-wave paroxysms with onset in the first 3 years of life were included. Patients with abnormal neurologic examination and brain imaging were excluded from the study. In our study, 39 patients met the clinical and electroencephalography (EEG) criteria of well-defined epileptic syndromes. Childhood absence epilepsy was found in 11 patients, benign myoclonic epilepsy in infancy in 18 patients, eyelid myoclonic epilepsy in 4, and epilepsy with myoclonic absences in 6. We did not find clinical and EEG criteria of well-recognized epileptic syndromes in seven children. Nine of 11 patients with simple absence seizures became seizure free. All these patients had normal neurologic and neuropsychological evaluations. Of the 35 patients who had absence seizures associated with myoclonic seizures, 20 became seizure free. Fifteen of 35 children continue having seizures. At the last visit, 20 of these 35 patients had normal neurologic and neuropsychological evaluations, 11 presented with mild mental retardation, and 4 with severe mental retardation. Epilepsies with absence seizures of early onset are relatively uncommon. Most of the patients had well-defined epileptic syndromes with a variable evolution. The evolution depended on the epileptic syndromes.

Symptoms and Clinical Course of Epilepsy with Myoclonic Absences

Symptoms and Clinical Course of Epilepsy with Myoclonic Absences

Absence seizures with myoclonic features in a juvenile Chihuahua dog

Long-term video-EEG was recorded for an eight-month-old Chihuahua dog with recurrent episodes of altered behaviour associated with head and nose twitching. Each episode lasted one to two seconds, multiple times per day before treatment. Ictal EEG showed generalised bilaterally synchronous 4 Hz spike-and-wave complexes during the "absence-like" event, along with rhythmically correlated head and nose twitching. We present video documentation of such attacks and discuss their similarities to human epilepsy with myoclonic absences.

Myoclonic status epilepticus in juvenile myoclonic epilepsy

Myoclonic status epilepticus (MSE) is rarely found in juvenile myoclonic epilepsy (JME) and its clinical features are not well described. We aimed to analyze MSE incidence, precipitating factors and clinical course by studying patients with JME from a large outpatient epilepsy clinic. We retrospectively screened all patients with JME treated at the Department of Neurology, Medical University of Innsbruck, Austria between 1970 and 2007 for a history of MSE. We analyzed age, sex, age at seizure onset, seizure types, EEG, MRI/CT findings and response to antiepileptic drugs. Seven patients (five women, two men; median age at time of MSE 31 years; range 17-73) with MSE out of a total of 247 patients with JME were identified. The median follow-up time was seven years (range 0-35), the incidence was 3.2/1,000 patient years. Median duration of epilepsy before MSE was 26 years (range 10-58). We identified three subtypes: 1) MSE with myoclonic seizures only in two patients, 2) MSE with generalized tonic clonic seizures in three, and 3) generalized tonic clonic seizures with myoclonic absence status in two patients. All patients responded promptly to benzodiazepines. One patient had repeated episodes of MSE. Precipitating events were identified in all but one patient. Drug withdrawal was identified in four patients, one of whom had additional sleep deprivation and alcohol intake. Two patients received inappropriate treatment (carbamazepine, phenytoin). MSE is a rare event in JME. Precipitating factors are commonly identified and for such cases the treatment response and outcome are excellent, in contrast to other cases with unknown causes.

Neck Myoclonia With Absence Seizures: Report of 3 Cases

Absence seizures associated with myoclonic phenomena can be seen in typical absences, myoclonic absences, eyelid myoclonia, and perioral myoclonia, all of which have diagnostic electroclinical features. The authors report 3 patients who encountered prominently rhythmic neck myoclonias with and without absences (loss of awareness). The descriptive symptoms of attacks by witnesses were head shaking or turning repeatedly instead of absences. The seizures were induced by hyperventilation in all 3 cases. Two cases had a history of previous febrile seizures. In all patients, video-electroencephalography showed a one-to-one correspondence relationship between the 2.5- to 3.5-Hz generalized spike and wave discharges and the rhythmic myoclonic jerks of the neck, which was further confirmed by sternocleidomastoideus electromyography recording in 1 patient. Seizures had been controlled by 1 or 2 antiepileptic drugs. Neck myoclonia with absences might be classified either as 1 special subtype of typical absence or as an independent seizure type. Paying close attention to the special phenomenon will help to clarify the clinical spectrum of this seizure.

Genes associated with idiopathic epilepsies: a current overview

Objective: This article aimed to review the latest genes associated with idiopathic focal and generalized epilepsies.Methods: PubMed and Entrez Gene searches pertaining to this work was conducted using specific keyword search terms related to genes and various listed subtopics related to idiopathic epilepsy syndromes.Results: Mutations in the cholinergic receptor, neuronal nicotinic, α2, α4 and β2 subunit genes have been found in autosomal dominant nocturnal frontal lobe epilepsy. Mutations of potassium voltage-gated channel, KQT-like subfamily, members 2 and 3 genes were identified to be responsible for benign familial neonatal seizures. The voltage-gated sodium channel genes and γ-aminobutyric acid receptor α subunit genes may be involved in the pathogenesis of generalized epilepsy with febrile seizure plus. Mutations of γ-aminobutyric acid receptor α1, γ-aminobutyric acid receptor δ, calcium channel voltage-dependent β4 subunit and chloride channel 2 gene are associated with juvenile myoclonic epilepsy. In addition, mutations of leucine-rich, glioma-inactivated 1 gene leads to genetic abnormalities of familial lateral temporal lobe epilepsy. EF-hand domain (C-terminal)-containing 1 gene can cause some patterns of juvenile myoclonic and juvenile absence epilepsies.Discussion: Genetic factors play an important role in idiopathic epilepsy syndromes. Ion channel genes and some non-ion channel genes contribute to the pathogenesis of idiopathic epilepsies. Based on these findings, genetic diagnosis and new treatment strategies to part of idiopathic epilepsies become possible in the future.

Familial epilepsy and developmental dysphasia: Description of an Italian pedigree with autosomal dominant inheritance and screening of candidate loci

To describe a familial epileptic condition combining a peculiar electro-clinical pattern with developmental language dysfunction in a large Italian kindred. We studied the clinical and neurophysiological features of a 4-generation family with 10 affected members (3 deceased). We also analysed in 7 affected and 7 healthy members microsatellite markers for 51 candidate loci for epilepsy, including 42 loci containing ion channel genes expressed in the brain, as well as the SPCH1 and SRPX2 loci. Five of the seven living affected members (aged 20-58 years) had the full phenotype (seizures, EEG epileptiform abnormalities and dysphasia). The language dysfunction was the first symptom, becoming evident since the period of language development and mainly consisting of phonemic and syntactic paraphasias, difficulty of expression and reduced verbal fluency. The seizures had their onset between 2 and 23 years and were reported as epileptic falls (4) associated or not with myoclonic features, absences (3), tonic-clonic (1) and complex partial seizures (1). The seizures were easily controlled by antiepileptic treatment in all patients except one. In the five patients with a good response of seizures to treatment, the EEG tracings showed the coexistence of focal and generalized epileptiform abnormalities; in the refractory patient the interictal EEG demonstrated bilateral asynchronous fronto-temporal paroxysms with left predominance and ictal SEEG recording suggested a multifocal origin of the discharges. MRI of the brain was normal in all patients. Linkage analysis provided negative LOD scores for all the investigated loci. We have described a novel familial pattern of epilepsy and developmental dysphasia which is not genetically linked to epilepsy or speech disorder loci, as documented by a candidate-gene linkage approach.

Myoclonic absence epilepsy with photosensitivity and a gain of function mutation in glutamate dehydrogenase

Activating mutations in glutamate dehydrogenase (GDH), de novo or dominantly inherited, are responsible for the hyperinsulinism/hyperammonemia (HI/HA) syndrome. Epilepsy has been frequently reported in association with mutations in GDH, but the epilepsy phenotype has not been clearly determined. Here, we describe a family with a dominantly inherited mutation in GDH. The mother, brother and both sisters had myoclonic absence seizures, but only the mother and one sister had the complete HI/HA pattern. For the two sisters with myoclonic absences, epilepsy started during the second year of life while the brother, it started at 6 years. All 3 children showed the same EEG pattern characterized by photosensitive generalized and irregular spike-wave discharges and runs of multiple spikes. The mother's EEG recordings were normal without photosensitivity. Magnetic resonance imaging (MRI) and spectroscopy (MRS) were normal. A direct effect of the GDH mutation, perhaps in combination with recurrent hypoglycemia and chronic hyperammonemia could provide a pathophysiological explanation for the epilepsy observed in this syndrome and these are discussed.

Myoclonic Status in Nonprogressive Encephalopathies: Study of 29 Cases

Myoclonic status in nonprogressive encephalopaties (MSNE) is characterized by recurrence of long-lasting myoclonic status appearing in infants and young children with nonprogressive encephalopathy. Here, we describe the electroclinical features and evolution of MSNE. Between February 1, 1990 and July 31, 2005, 29 patients who met diagnostic criteria of MSNE were enrolled in the study at our department and have been followed up to the present time. Three main subgroups could be identified. The first subgroup of 18 patients presented myoclonic absences and rhythmic myoclonias. These were followed by a brief silent period related to a subcontinuous delta-theta activity involving the central areas, and rhythmic delta waves with superimposed spikes mainly involving the parietooccipital regions and often activated by eye closure. It was found in all children with a genetic etiology. The second subgroup included five patients showing a pattern characterized by inhibitory phenomena associated with a dystonic component and sudden irregular rapid lightning-like jerks. The EEG showed subcontinuous multifocal slow spike-waves, predominating in frontocentral regions. These patients are affected by a cortical malformation or the etiology is unknown. The third subgroup included six children who initially suffered from myoclonic absences. The status was initially characterized by subcontinuous generalized spike-wave-type paroxysms related to rhythmic myoclonia of face and limbs. After 1-3 weeks, the EEG showed sharp theta waves with very slow pseudorhythmic continuous spikes in the central regions and vertex. The etiology was found to be perinatal anoxic injury. MSNE should be considered as a new epileptic syndrome in the group of epileptic encephalopathy.

Epilepsy with myoclonic absences

Epilepsy with myoclonic absences is a rare seizure disorder with intellectual impairment and resistance to conventional anti-convulsants. It is essential to diagnose epilepsy with myoclonic absences earlier for a better outcome. The authors present a case report to highlight this fact.

Levetiracetam in patients with generalised epilepsy and myoclonic seizures: An open label study

To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.

Juvenile myoclonic epilepsy in an elderly patient

Juvenile myoclonic epilepsy constitutes 5-10% of idiopathic generalised epileptic syndromes. The clinical triad of absence seizures, myoclonic jerks and generalised tonic clonic seizures (GTCS) rarely begin after the second decade of life. We present the case of a 74-year-old lady presenting for the first time with myoclonic jerks and absences. The electro encephalogram revealed generalised polyspike and wave epileptiform activity with photosensitivity. On close questioning, she appeared to have had a single episode of GTCS at the age of 10. She remained asymptomatic for 64 years before the diagnosis was made. Although rare, idiopathic myoclonic epilepsy could remain asymptomatic for decades and can present in the elderly. Proper classification of this epileptic syndrome, even in the elderly, is essential in view of the response to appropriate antiepileptic therapy.

Early-onset absence epilepsy: Clinical and electroencephalographic features in three children

To describe the clinical and electroencephalographic features of three infants diagnosed as having early-onset absence seizures. Two males and one female, aged 21–29 months were seen in our neuropaediatric outpatient clinic because of daily episodes of motor arrest and loss of contact. Neurological examination and mental development was considered normal in all of them. Two out three had first-degree relatives with seizures with onset in the childhood and favourable evolution in the adulthood. A video-electroencephalogram was requested. Ictal EEG revealed a normal background and generalised spike-and-wave complexes at 3–3.5 Hz accompanied by disruption of ongoing activity in keeping with absence seizures. The duration of seizures ranged from 2 to 10 s. One child (patient 2) experienced rhythmic myoclonic jerks in upper limbs and head as those described in myoclonic absences. Clinical and electroencephalographic follow-up ranged from 8 months to 4 years. Two children were on treatment with valproate and in the case of the patient 3, the combination of valproate and ethosuximide was necessary. Control of absence seizures was achieved in all our cases. Absence seizures should be considered as a possible cause of transient impairment of consciousness even among infants minor than 3 years of age. A video-electroencephalogram is the method of choice in the diagnostic evaluation and syndromic classification of these paroxysmal events.

Epilepsy with Myoclonic Absences

Among the epileptic syndromes that are defined mainly on the basis of a characteristic seizure type, epilepsy with myoclonic absences (EMA) stands out as a somewhat controversial entity. This is because the sound and evident clinical characteristics on which it was identified some 30 years ago have evolved, mostly as a consequence of changes in the practical management of epilepsies and to the description of myoclonic components in a variety of other generalised epilepsies with absences. Myoclonic absences (MA) are described as typical absences with sudden onset and offset that are associated with generalised spike and wave (SW) discharges on the ECG, with distinctive traits. Clinically, absences are associated with axial hypertonia (the subject usually bends forward and slightly raises their shoulders and arms), and jerks synchronous with the SW discharges. Neurophysiologically, axial hypertonia and rhythmic jerks may be recorded on polygraphic surface electromyogram leads in association with the typical SW discharges; as such, despite an ECG, the diagnosis may be missed in the absence of video documentation of the seizure and/or adequate polygraphy. MA need to be distinguished from absences with other types of prominent myoclonic accompaniment (perioral, eyelid, limbs).The prognosis of EMA remains variable. Modern therapeutic combinations, such as valproic acid and ethosuximide, or valproic acid and lamotrigine, are usually effective; however, in a proportion of patients, seizures are resistant to drug treatment. These patients may experience cognitive deterioration and, in some cases, evolution towards a more severe form of epilepsy, including the Lennox-Gastaut syndrome. The more benign cases usually present with MA as the only seizure type, while patients who experience other seizures, especially generalised tonic-clonic seizures, in association with MA may have a less favourable outcome.

Idiopathic Generalized Epilepsies Recognized by the International League Against Epilepsy

There are eight syndromes currently recognized by the International League Against Epilepsy (ILAE) that would fit the original operational definition of idiopathic generalized epilepsy (IGE) syndromes, including benign myoclonic epilepsy in infancy; generalized epilepsy with febrile seizures plus, an entity in evolution; epilepsy with myoclonic absences; epilepsy with myoclonic-astatic seizures; childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and epilepsy with generalized tonic-clonic seizures only. All of these syndromes can be easily diagnosed when distinctive features are present. In some cases, such features are not present or only appear later in the course of the disease, making it challenging to distinguish the various syndromes. Electroencephalogram (EEG) is the most helpful laboratory test and often will strongly support the diagnosis of IGE, but may not be very helpful in discriminating between several of the syndromes with overlapping features. The same applies for genetic testing, although it is expected that further research exploring the genotype-phenotype relationships will enhance our abilities to make definitive diagnoses. At the current time, clinical features are still the cornerstone of accurate classification, and accurate classification, in turn, is the best predictor of outcome.

Anoxic-epileptic seizures: observational study of epileptic seizures induced by syncopes

Aims: To describe a large series of children with anoxic-epileptic seizures (AES)—that is, epileptic seizures induced by syncopes. Methods: Retrospective case-note review in a tertiary paediatric neurology unit. For all...