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Background: The epileptic encephalopathies collectively exact an immense personal, medical, and financial toll on the affected children, their families, and the healthcare system. Objective: This study was aimed to delineate the clinical spectrum of patients with Epileptic encephalopathies (EEs) and classify them under various epileptic syndromes. Methods: This was a cross-sectional study that was carried out in the department of Neurophysiology of the National Institute of Neurosciences and Hospital, Bangladesh from July 2016 to June 2019. Children with recurrent seizures which were difficult to control and associated with developmental arrest or regression in absence of a progressive brain pathology were considered to be suffering from EE. Children under 12 years of age fulfilling the inclusion criteria were enrolled in the study. These patients were evaluated clinically and Electroencephalography (EEG) was done in all children at presentation. Based on the clinical profile and EEG findings the patients were categorized under various epileptic syndromes according to International League Against Epilepsy (ILAE) classification 2010. Results: A total of 1256 children under 12 years of age were referred to the Neurophysiology Department. Among them, 162 (12.90%) fulfilled the inclusion criteria. Most of the patients were male (64.2%) and below 1 year (37.7%) of age. The majority (56.8%) were delivered at the hospital and 40.1% had a history of perinatal asphyxia. Development was age-appropriate before the onset of a seizure in 38.9% of cases. Most (53.7%) of the patients had seizure onset within 3 months of age. Categorization of Epileptic syndromes found that majority had West Syndrome (WS) (37.65%) followed by Lennox-Gastaut syndrome (LGS) (22.22%), Otahara syndrome (11.73%), Continuous spike-and-wave during sleep (CSWS) (5.66%), Myoclonic astatic epilepsy (MAE) (4.94%), Early myoclonic encephalopathy (EME) (3.7%), Dravet syndrome (3.7%) and Landau-Kleffner syndrome (LKS) (1.23%). 9.26% of syndromes were unclassified. Conclusion: EEG was found to be a useful tool in the evaluation of Epileptic encephalopathies. The clinico-electroencephalographic features are age-related. Their recognition and appropriate management are critical.

The purpose of this series is to briefly highlight a range of rare health conditions. Rare health conditions are those that affect no more and usually fewer than 1 person in every 2000 and many HCAs and nurses will encounter some of these conditions, given the high number of these conditions. This 20th article will briefly explore three of these conditions, focussing on rare forms of epilepsy.

The glucose transporter type 1 (Glut1) is the most important energy carrier of the brain across the blood-brain barrier. In the early nineties, the first genetic defect of Glut1 was described and known as the Glut1 deficiency syndrome (Glut1-DS). It is characterized by early infantile seizures, developmental delay, microcephaly, and ataxia. Recently, milder variants have also been described. The clinical picture of Glut1 defects and the understanding of the pathophysiology of this disease have significantly grown. A special form of transient movement disorders, the paroxysmal exertion-induced dyskinesia (PED), absence epilepsies particularly with an early onset absence epilepsy (EOAE) and childhood absence epilepsy (CAE), myoclonic astatic epilepsy (MAE), episodic choreoathetosis and spasticity (CSE), and focal epilepsy can be based on a Glut1 defect. Despite the rarity of these diseases, the Glut1 syndromes are of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms especially if it is started as early as possible. The present article summarizes the clinical features of Glut1 syndromes and discusses the underlying genetic mutations, including the available data on functional tests as well as the genotype-phenotype correlations. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

OBJECTIVE: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE).METHODS: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies.RESULTS: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each.SIGNIFICANCE: MAE is associated with significant neurodevelopmental impairment. MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity.

Purpose To report novel clinical manifestations of KCNA2 mutation related epileptic encephalopathy. Methods Blood samples were sent for whole exome and Sanger sequencing. Seizure types were characterized by clinical criteria and EEG recording. Results KCNA2 mutations have been reported in 10 cases who presented with focal, absence, generalized tonic-clonic or myoclonic astatic seizures. Here we describe 3 patients with previously unreported, more severe manifestations. Patient 1 is a 5 year-old male with a c.1214 C > T (p.Pro405Leu) mutation, previously reported to be disease causing. He presented at 1year of age with focal seizures and subsequently developed electrical status epilepticus of sleep at age 3. The latter finding to our knowledge has never been reported in patients with KCNA2 mutations. Patient 2 is a 7 year-old female with a novel c.1195 G > A (p.Val399Met) mutation not previously described. She presented with intermittent then continuous polymyoclonus and myoclonic-astatic and generalized tonic clonic seizures. Continuous polymyoclonus is another new manifestation in patients with KCNA2 mutations. Patient 3 is a 23 year-old male with a c.889C > T (p.Arg297Trp) mutation not previously described. He presented at 4 years of age with generalized tonic clonic seizures and later developed recurrent refractory status epilepticus episodes at ages 19, 22 and 23 years, the latter being a novel manifestation in patients with KCNA2 mutations. Conclusion We identified 3 patients with KCNA2 mutations with novel characteristics, including electrical status epilepticus of sleep, continuous polymyoclonus and status epilepticus. These results expand KCNA2 mutation epileptic manifestations to include more severe, previously unreported phenotypes.

OBJECTIVE: Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.METHODS: We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.RESULTS: Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).SIGNIFICANCE: Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.

The phenotypic spectrum of glucose transporter type 1 (GLUT1) deficiency syndrome is now known to be a continuum that includes the classic phenotype as well as atypical childhood absence epilepsy, myoclonic astatic epilepsy, and paroxysmal nonepileptic findings such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia. We report the case of a mentally normal child with history of infantile seizures, which remitted but later developed nonepileptic movement disorder, responsive to carbohydrate intake, with a novel frameshift mutation (c.1344_1347delCTAC p.Y449fs) in the last exon of the GLUT1 gene. This case further broadens the phenotypic spectrum of GLUT1 deficiency syndrome. We provide evidence from this case and previous reports that mutations affecting the length and composition of the intracellular C-terminal domain of the GLUT1 protein have a variable and somewhat unpredictable range of pathological effects. These range from null phenotypes associated with C-terminal domain absence, to milder presentations associated with C-terminal domains comprising partially and (in this case study) completely abnormal amino acid sequences.

Glucose transporter 1 deficiency syndrome (GLUT-1 DS) is a unique genetic syndrome representing a severe metabolic encephalopathy, as a result, of insufficient glucose transport into the brain. Infantile onset seizures, acquired microcephaly, spasticity, ataxia, dystonia and mental retardation are the cardinal features of the syndrome. Over the years, the clinical spectrum of GLUT-1 DS has been expanded beyond the original phenotype. Clinical features of seizures present with a wide spectrum, however generalized seizures are reported as the most common seizure types in the patients received diagnosis of GLUT-1 DS. In recent years, there are number of epilepsy syndromes described in association with GLUT-1 DS has been shown to be the underlying cause for 10% of early onset absence epilepsy, 5% of Myoclonic astatic epilepsy (MAE) and 1% of idiopathic generalized epilepsies. Seizures are often remained refractory despite the treatment with a number of antiepileptic medications. Valproate and benzodiazepines are relatively contraindicated for the treatment of seizures in this syndrome. Ethanol and caffeine also inhibits GLUT-1 transport activity and may exacerbate seizures. Ketogenic diet remains the most effective treatment in order to meet the energy demand of developing brain. GLUT-1 DS should be suspected in the individuals with family history of idiopathic generalized epilepsy and/or paroxysmal dyskinesia. Moreover, the families with absence epilepsy with a wide range of age of onset or seizure types should also be screened for GLUT-1 DS.

Antiepileptic drugs may occasionally increase seizure frequency or eliciting de novo seizure occurrence; the underlying mechanism of these effects is not known. The potential adverse effects of valproic acid in myoclonic astatic epilepsy have been noted by experienced clinicians in various different regions of the world, but this important observation has not been sufficiently reported. We present the case of tonic status epilepticus in an 8-year-old boy with Doose syndrome related to valproic acid. Valproic acid, such as others antiepileptic drugs, is liable to produce paradoxical effects such as the atypical seizures we report. We emphasize the importance for the management of acute seizures in an intensive care unit setting and increase awareness of the acute toxic effects of antiepileptic drugs.

An electroclinical epilepsy syndrome diagnosis enables physicians to predict outcomes as well as select appropriate treatment options. We report a child who presented with reflex myoclonus at the age of 9 months and was initially diagnosed with myoclonic epilepsy in infancy. After 9 years of medically resistant myoclonic seizures, extensive investigations, and emerging learning difficulties, she was referred for video-telemetry to characterize her seizures in an attempt to make a syndromic diagnosis. A three-day video-telemetry assessment was performed to document seizures. Neck and deltoid EMG channels were applied from the onset of the recording. Frequent generalized bursts of 3- to 5-Hz spike/polyspike and slow wave discharges, associated with clinical manifestations, mostly myoclonic seizures, were noted. In addition, definite atonic components were noted on the neck EMG as well as the deltoids associated with the slow component of the ictal discharges. The EEG and polygraphy findings are suggestive of a generalized epilepsy characterized by predominantly myoclonic seizures with atonic components. This raises the possibility whether a variant of epilepsy with myoclonic–atonic seizures (Doose syndrome) may be the underlying diagnosis for this girl. A trial of the ketogenic diet would therefore be considered as an option in her future management in view of its beneficial effect in this condition.

SummaryObjective Children with myoclonic astatic epilepsy (MAE; Doose syndrome) whose seizures do not respond immediately to standard antiepileptic drugs (AEDs) are at high risk of developing an epileptic encephalopathy with cognitive decline. A classic ketogenic diet (KD) is a highly effective alternative to AEDs. To date, there are only limited data on the effectiveness of the modified Atkins diet (MAD), which is less restrictive and more compatible with daily life. We report findings from a retrospective study on 30 MAE patients treated with MAD. Methods Four participating centers retrospectively identified all patients with MAE in whom a MAD had been started before June 2015. Seven children were recruited from a cohort included in an open prospective controlled trial. A retrospective review of all available charts was performed in the other patients. Results Thirty patients (24 boys) were included. Mean age at epilepsy onset was 3.1 years (range 1.5–5.6). MAD was started at a mean age of 4.5 years (range 2.2–9.1) after the children had received an average of six different AEDs (range 2–15). Mean MAD observation time was 18.7 months (range 1.5–61.5). Twenty of 30 patients were still on MAD at the end of study (duration range 1.5–61.5, mean 18.5 months). MAD was stopped without relapse in three patients after sustained seizure freedom for >2 years. For the other seven cases, ineffectiveness (three patients), loss of efficacy (two), or noncompliance (two) led to termination. No severe adverse effects were noted. By the end of the observation period, 25 (83%) of 30 patients experienced a seizure reduction by ≥50% and 14 (47%) of 30 were seizure-free. None of the evaluated factors differed significantly between the groups of seizure-free and non–seizure-free children. Significance MAD is an effective treatment for MAE. It should be considered as an alternative to AEDs or the more restrictive classic ketogenic diet.

Structured online surveys were used to explore the experiences of the parents of children with refractory epilepsy using medicinal cannabis in Mexico during September 2016. The surveys, which were completed in full, were reviewed, and 53 cases of children aged between 9 months and 18 years were identified. Of these, 43 cases (82%) were from Mexico and 10 (18%) were from Latin American countries. Of the 43 Mexican cases, the diagnoses were as follows: 20 cases (47%) had Lennox-Gastaut syndrome (LGS); 13 cases (30%) had unspecified refractory epilepsy (URE); 8 cases (19%) had West syndrome (WS); 1 case (2%) had Doose syndrome (DS); and 1 case (2%) had Ohtahara syndrome (OS). In total, 47.1% of cases had previously been treated with 9 or more anticonvulsant therapies. The parents reported a decrease in convulsions when cannabidiol was used in 81.3% of the cases; a moderate to significant decrease occurred in 51% of cases, and 16% of cases were free from seizure. The number of antiepileptic drugs being used was reduced in 9/43 (20.9%) cases. No serious adverse effects were reported, with only some mild adverse effects, such as increased appetite or changes in sleep patterns, reported in 42% of cases. © 2017 Carlos G. Aguirre-Velázquez.

Ketogenic Dietary Therapies (KDT) are an effective treatment option for some people with drug-resistant epilepsy. They are, however, resource-intensive and can cause adverse side effects. Predictors of response would improve the selection process and perhaps further our understanding of the mechanisms behind dietary treatments for epilepsy. We conducted a literature review to identify factors that may influence response to KDT. We found no strong evidence that there are any specific factors that affect response. Gender and intellectual status do not seem to affect response; evidence is inconsistent for all other factors. Experimental studies may point us in the right direction for future work.

The ketogenic diet is not a new treatment for the treatment of epilepsy, but the degree of literature now available seems to have given it a new lease of life. Over the past 12 years, there has been more scientific data on both benefits and effect of the ketogenic diet. Data demonstrate a clear benefit in efficacy. We also have a clearer idea in utilization, type of diet to use, and in whom. Questions however remain and further work is required, not least in recognizing likely candidates and in simplifying administration.

Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of conditions characterized by epileptic seizures that are difficult to treat and developmental delay. In this review, we discuss the ongoing debate regarding the significance of inter-ictal discharges and the impact of the seizures themselves on the cognitive delay or regression that is a common feature of these syndromes. The syndromes also differ in many ways and we provide a summary of the key features of the early-onset epileptic encephalopathies including Ohtahara and West syndromes in addition to later childhood-onset syndromes such as Lennox Gastaut and Doose syndromes. An understanding of the various severe epilepsy syndromes is vital to understanding the rationale for treatment. For example, the resolution of hypsarrhythmia in West syndrome is associated with an improvement in cognitive outcome and drives treatment choice, but the same cannot be applied to frequent inter-ictal discharges in Lennox Gastaut syndrome. We discuss the evidence base for treatment where it is available and describe current practice where it is not. For example, in West syndrome there is some evidence for preference of hormonal treatments over vigabatrin, although the choice and duration of hormonal treatment remains unclear. We describe the use of conventional and newer anti-epileptic medications in the various syndromes and discuss which medications should be avoided. Older possibly forgotten treatments such as sulthiame and potassium bromide also have a role in the severe epilepsies of childhood. We discuss hormonal treatment with particular focus on the treatment of West syndrome, continuous spike wave in slow wave sleep (CSWS)/electrical status epilepticus in slow wave sleep (ESES) and Landau Kleffner syndrome. The role of the ketogenic diet has in recent years come to the fore of the management of these severe epilepsies and we describe successful use in myoclonic astatic epilepsy, Lennox Gastaut syndrome and Dravet syndrome. It is important that resective epilepsy surgery is not ignored in the management of these children, particularly those with hemi-pathology who may present with ESES and respond well to hemispheric disconnection. Adjunctive and symptomatic surgical treatments such as vagal nerve stimulation and corpus callosotomy may improve seizure burden. Finally, it is vital that the identification and treatment of developmental, behavioural and psychiatric co-morbidities are not neglected and that a rational, holistic approach is taken to the management of epileptic encephalopathies.

Background Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. Methods We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. Results The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. Conclusion A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration.

Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first description. However, although the International League Against Epilepsy (ILAE) defined criteria for MAE in 1989, the diagnostic boundaries of the syndrome continue to be debated. Moreover, 40 years since Doose's first description of MAE, although a genetic predisposition is acknowledged and many studies have demonstrated familial aggregation of seizures within MAE families, the actual genetic determinants of MAE still remain unknown. Although initially thought to be within the same spectrum as severe myoclonic epilepsy of infancy, the exclusion of SCN1A mutations in non-generalized epilepsy with febrile seizures plus (GEFS+) MAE cases has confirmed the genetic distinction of MAE. In this critical review, we shall trace the historical evolution of concepts around MAE and its distinction from Lennox-Gastaut syndrome, review the described phenotypic features of MAE from updated studies that will allow its distinction from other overlap epilepsy syndromes, review the evidence of genetic influences and clues for genetic heterogeneity, and discuss strategies that may be helpful in elucidating the etiology of MAE in light of current genetic techniques.

We have used intravenous immunoglobulin to treat pediatric patients with various severe epileptic conditions. This retrospective, multicenter study comprised 64 consecutive patients treated with immunoglobulins for either epileptic encephalopathy or refractory epilepsy. The rate of full or partial improvement according to specific syndrome involved three of four patients with idiopathic West syndrome, six of 12 patients with electrical status epilepticus in sleep, eight of 19 patients with an undefined syndrome, one of three patients with Landau-Kleffner syndrome, and one of two patients with Rasmussen encephalitis. Intravenous immunoglobulins were ineffective in 10 patients with symptomatic West syndrome, nine with febrile infection-related status epilepticus, three with myoclonic astatic epilepsy, and two with Lennox-Gastaut syndrome. Nine patients (14%) demonstrated complete resolution, and 10 (15.6%) exhibited partial improvement. Of these 19 responders (29.7%), eight relapsed. Although intravenous immunoglobulin is not suitable for all cases of epilepsy, it may prove efficacious for specific epileptic syndromes, mainly idiopathic West syndrome and electrical status epilepticus during sleep.

Myoclonic epilepsy in infancy (MEI) is a primary generalized epilepsy. According to the literature, the outcome of MEI is usually benign. Here we report a patient who developed myoclonic astatic epilepsy at age four, having been seizure free without antiepileptic drug treatment for 2 years after his recovery from MEI. At age four, a video-EEG-recording showed frequent head nodding (atonic seizures) and myoclonic astatic seizures associated with diffuse spikes or polyspikes and waves. The interictal EEG revealed frequent bursts of generalized 100–200μV, 2–4Hz spike-and-slow-wave complexes. Despite a general favorable outcome, more severe epilepsy syndromes may develop after MEI, and mental retardation is sometimes observed. Our case and the previous literature suggest that epilepsies following on from MEI often involve myoclonic seizures.

The objective of the study was to explore clinical, electroencephalography (EEG), neuropsychological features and prognosis of myoclonic-astatic epilepsy (MAE). Of 327 children aged between 1 and 9 years with a diagnosis of generalized epilepsy followed between 2000 and 2008, 18 (5.5%) had MAE. Male significantly predominated (88.9%). Age at onset ranged from 2.3 to 4.9 years (mean 3.6 years). Median follow-up period was 6.3 years. In addition to myoclonic-astatic seizures patients had myoclonic seizures (66.7%), drop attacks (72.2%), head drops (77.8%) absences (88.9%), tonic-clonic generalized seizure (77.8%), tonic seizures (38.9%), non-convulsive status epilepticus (16.7%). Seven patients (38.9%) had an epileptic encephalopathy. At onset, interictal epileptiform and slow abnormalities were recorded, respectively, in 100% and 77.8% of patients. EEG abnormalities disappeared in all patients within 4 years since the onset. At long-term follow-up, two patients developed focal abnormalities typical of rolandic epilepsy and two patients photosensitivity. On neuropsychological testing 66.7% of patients had a normal IQ (mean 81.2±17.0, range 47-105, median 84.5) after a mean period of 4.4 years since the last seizure. Sixteen out of 18 patients remitted within 3.5 years since the onset and in two patients tonic seizures persisted. MAE is generalized childhood epilepsy: although cognitive functions might deteriorate, outcome is good regarding seizures.

Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970. In 1989, the International League Against Epilepsy classified it formally as a symptomatic generalized epilepsy, and 20 years later it was renamed 'epilepsy with myoclonic-atonic seizures'. In this review, we discuss the components of this unique disorder including its incidence, clinical features, and electroencephalographic findings. Recent evidence has suggested possible genetic links to the GEFS+ (generalized epilepsy with febrile seizures plus) family, and, additionally, some children with structural brain lesions can mimic the Doose syndrome phenotype. Treatment strategies such as corticosteroids, ethosuximide, and valproate have been described as only partially effective, but newer anticonvulsants, such as levetiracetam and zonisamide, may provide additional seizure control. The most effective treatment reported to date appears to be the ketogenic diet. Prognosis is quite varied in this disorder; however, many children can have a remarkably normal neurodevelopmental outcome.

Seizures in infancy are common. Although there are a number of clearly defined epilepsy syndromes which begin or occur in infancy many infants cannot be readily classified into currently recognised epilepsy syndromes. This review discusses the clinical presentation, EEG findings, natural history and management of several recognisable epilepsy syndromes in infancy. Special syndromes including febrile convulsions and symptomatic seizures are discussed. There is also advice about investigation of seizures and syndromes in this population.

A total of 142 patients (84 per cent aged less than 20 years) with various forms of generalized epilepsy have been treated with sodium valproate alone or in combination with other drugs. The mean duration of symptoms was six years, and half the patients had daily seizures. Nine patients had typical absences, 33 had absences with automatisms, 28 had tonic-clonic seizures with or without photosensitivity, and 72 had various forms of myoclonic epilepsy. Dosage varied from 23 to 54mg/kg and twice-daily administration was usual. Estimation of serum levels did not assist in management. Fits ceased in 63 per cent of all cases and a further 18 per cent showed improvement greater than 50 per cent. Of the 69 with 3c/sec spike-and-wave discharges, 81 per cent became free from all fits, as did 77 percent of those with myoclonic jerks. Fits ceased in eight of the 32 patients with myoclonic astatic epilepsy and there was improvement greater than 50 per cent in a further eight patients. Other anticonvulsants were often withdrawn and always reduced. 21 patients received sodium valproate alone from the start of treatment and all other drugs were withdrawn in another 38. Sodium valproate alone controlled all fits in four children with absences, in 18 with absences with automatisms, 10 with tonic-clonic seizures and 22 with myoclonic epilepsy. Side-effects were rare, mild and often temporary. Potentiation of barbiturates and benzodiazepines occurred, especially clonazepam, which should be avoided. Many patients were more alert. Sodium valproate appears to be the drug of choice for epilepsies associated with generalized spike-and-wave discharges, myoclonic epilepsies or photosensitive epilepsies, and is of especial value in children and mentally retarded patients because it lacks sedating effects and often induces liveliness.

Resume Introduction Le syndrome de Sturge-Weber est un syndrome neurocutane qui associe un angiome plan facial et un angiome pial. Il est responsable d’epilepsie partielle. Dans de tres rares cas, des crises epileptiques generalisees ont ete rapportees. Observation Nous rapportons l’observation d’une fillette, âgee de quatre ans qui presente un syndrome de Sturge-Weber. La premiere crise epileptique partielle survint a l’âge de trois ans avec une evolution vers un etat de mal refractaire. Au decours de cet episode, le traitement comprenait un regime cetogene et une tritherapie antiepileptique. Aucune crise epileptique n’a ete observee pendant quatre mois. Plusieurs types de crise sont ensuite reapparus : des crises myocloniques, des crises cloniques partielles et des chutes. L’anamnese ne permettait pas de preciser le type de crise entrainant les chutes. Un enregistrement video-electroencephalographique prolonge a permis de mettre en evidence des crises myoclonoastatiques. Conclusion Les crises epileptiques dans le syndrome de Sturge-Weber sont le plus souvent des crises partielles. Quatre patients presentant un syndrome de Sturge-Weber avec crises myoclonoastatiques ont ete decrits dans la litterature. A partir de cette observation, nous discuterons les hypotheses pouvant conduire d’une anomalie focale a des crises generalisees de type myoclonoastatique.

Seizure disorders are relatively common in childhood, and the International League Against Epilepsy (ILAE) provides a hierarchical classification system to define seizure types. At the final level of classification, specific epilepsy syndromes are defined that represent a complex of signs and symptoms unique to an epilepsy condition. The present review discusses the issues related to several of these epilepsy syndromes in childhood, including those classified as generalized idiopathic epilepsies (e.g., childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy), focal epilepsies (benign rolandic epilepsy, occipital epilepsy, temporal lobe epilepsy, frontal lobe epilepsy) and the "epileptic encephalopathies," including Dravet's Syndrome, West Syndrome, Lennox-Gastaut Syndrome, Myoclonic Astatic Epilepsy, and Landau-Kleffner Syndrome. For each syndrome, the epidemiology, clinical manifestations, treatments, and neuropsychological findings are discussed.

Summary: Purpose: Myoclonic astatic epilepsy (MAE) is a generalized epilepsy of early childhood. Little is known about the use of newer antiepileptic treatments (AET) in MAE. The purpose of this study was to describe the characteristics, treatment, and outcome of a contemporary MAE cohort exposed to the new generation AET. Methods: Charts of subjects with MAE treated between 1998 and 2005 were reviewed. Results: Twenty-three subjects (19 boys), with a median (range) follow-up of 38 (2‐ 86) months were identified. Thirtynine percent had a family history of epilepsy, and 39% had family history of febrile seizures. Age at seizure onset was a median of 36 (12‐24) months. Initial EEG was normal in 30%. When seizures ceased, EEG background and epileptiform abnormalities persisted in 17 and 58%, respectively. On average, each subject was exposed to five AET. The most frequently used AET was valproate (83%). Seizure freedom occurred spontaneously in three subjects, with ethosuximide and levetiracetam in one each, valproate and lamotrigine in two each, topiramate in three and the ketogenic diet (KD) in five subjects. By 36 months after seizure onset, 67% achieved seizure freedom. At the last visit, 43% were developmentally normal, 52% had mild, and 5% had moderate cognitive disabilities. Time to seizure freedom did not correlate with cognitive outcome. Conclusions: The new generation of AET may offer significant benefit to children with MAE. The KD was the most effective AET in this series, and perhaps should be considered earlier in treatment. Key Words: Myoclonic astatic epilepsy—Idiopathic generalized epilepsy— Antiepileptic drugs—Ketogenic diet. Myoclonic astatic epilepsy (MAE) of Doose is a generalized epilepsy syndrome of young children characterized by multiple seizure types—predominantly myoclonic seizures (MS), astatic seizures (AS), and myoclonic astatic seizures (MAS), as well as with generalized tonic‐clonic (GTC), absence, myoclonic absence, and tonic seizures (Doose, 1992). In general, children are developmentally normal before the onset of epilepsy and organic brain abnormalities are absent. The seizures are often difficult to treat, but may remit spontaneously. EEG tracings may be normal initially, but later develop a characteristic biparietal theta background rhythm, and irregularly generalized spike wave, and polyspike wave discharges. Long-term prognosis varies from cessation of seizures with normal developmental outcome to intractable epilepsy with mental retardation. Favorable outcomes were reported in half to two-thirds of cases (Doose, 1992; Kaminska et al., 1999; Oguni et al., 2002 ). A relationship between poor control of seizures and cognitive

Summary The first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood-brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of epilepsy including early onset absence epilepsy (EOAE), myoclonic astatic epilepsy (MAE), and genetic generalized epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of epilepsy including MAE and absence epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.

Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.

Myoclonic astatic epilepsy (MAE) is a rare childhood generalized epilepsy syndrome of unknown incidence and etiology. Onset may be explosive with a myriad of different seizure types and children may become severely affected with an epileptic encephalopathy. This disorder may be particularly sensitive to the ketogenic diet (KD). This article will briefly review the background, diagnostic criteria's and our current information regarding the use of dietary therapies in MAE.

Purpose : To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria, using multiple correspondence analysis (MCA). Methods : We applied MCA to a series of 72 children with no evidence of brain damage, starting epilepsy between 1 and 10 years, with two or more types of generalised seizures. We excluded patients with infantile spasms or typical absences. MCA was performed on all clinical and EEG parameters, first throughout follow-up, then restricted to the first year of the disease. Results : When including all follow-up variables, there were three groups: (1) Thirty-seven children with male predominance, familial history of epilepsy, simple febrile convulsions, massive myoclonus, tonic–clonic fits. Outcome was favourable, with no seizures and mildly affected cognitive functions. Interictal EEG showed short sequences of irregular 3-Hz spike-waves. (2) In 18 children, clinical characteristics were similar to those of the first group at the early stage, but 95% exhibited myoclonic status and vibratory tonic seizures, with persisting seizures on follow-up. EEG showed long sequences of generalised irregular spike and slow waves. Those two groups meet the characteristics of childhood onset myoclonic-astatic epilepsy (MAE) with respectively, favourable and unfavourable outcome. (3) Eleven children had later onset, atypical absences, tonic and partial seizures, and no myoclonus, or vibratory tonic seizures. All had mental retardation and persisting seizures. EEG showed long sequences of slow spike-wave activity and half the patients had spike and slow wave foci. These patients met the major characteristics of Lennox–Gastaut syndrome. Initial parameters failed to distinguish the first two groups, but Lennox–Gastaut syndrome (the third group) was distinct from both groups of myoclonic astatic epilepsy from the onset. Within MAE groups combined, clinical and EEG risk factors for mental retardation could be identified. Conclusion : It is possible to validate statistically the distinction between discrete epileptic syndromes. Myoclonic astatic epilepsy is therefore distinct from Lennox–Gastaut syndrome, and the distinction appears from the first year of the disorder.

A child with Sturge-Weber syndrome and a left occipital leptomeningeal angioma developed focal seizures at 6 years of age that responded initially to oxcarbazepine. After 7 months of seizure freedom, the patient developed typical myoclonic-astatic seizures associated with generalized electrographic discharges, which worsened as oxcarbazepine was increased. The seizures and electroencephalogram improved dramatically in 3 weeks as the oxcarbazepine was withdrawn and valproic acid was initiated. This case demonstrates the importance of recognizing that children with epilepsy due to focal lesions can develop secondary bilateral synchrony that can be aggravated by medications that are effective for partial seizures. In such cases, treatment with a broad-spectrum antiepileptic may be advantageous.

Glucose transporter-1 deficiency syndrome (GLUT1-DS, OMIM 606777) is a treatable hereditary disorder of brain energy metabolism caused by heterozygous mutation in SLC2A1 gene on chromosome 1p34. Resulting deficient GLUT1 protein is responsible for impaired GLUT-1 mediated glucose transport into the brain clinically leading to a wide range of neurological symptoms. We report on a 15 years old male with genetically confirmed glucose transporter type 1 deficiency syndrome (GLUT1-DS; DYT9/DYT18). Developmental delay was already present before two years of age. Sudden episodes of exercise induced weakness without loss of consciousness were assumed to be myoclonic astatic epilepsy or atypical absences and therefore treated with valproinic acid and later with ethosuximide, both ineffectively. Hypoglycorrhachia and decreased CSF to blood glucose ratio found at the age of 14 years finally led to subsequent direct sequencing of SLC2A1 gene. Standard treatment in GLUT1-DS is ketogenic diet. Modified Atkins Diet (MAD) is an alternative ketogenic diet with the advantages preserving acceptable nutrition and obtaining compliance in adolescent patients. MAD has been described to improve movement disorder, seizures, alertness, cognitive abilities, and electroencephalography findings in GLUT1-DS in children. In our adolescent patient MAD was initiated in January 2015 to ameliorate symptoms such as movement disorder, paroxysmal exercise-induced dyskinesia, hypokinesia, tremor, rigor, spasticity and intellectual disability. In spite of abnormal EEG findings, symptomatic epilepsy has never been the leading symptom in this patient. We assume that even late treatment initiation of MAD in this adolescent patient could ameliorate movement disorder, cognitive function and EEG findings. Presenting this case report we will discuss actual literature concerning ketogenic diet in GLUT1-DS.

Based on small numbers of patients, it is possible to make the following suggestions rather than categorical statements. For myoclonic seizures and epilepsies which are not otherwise specified, valproate seems of proven efficacy. Ethosuximide may be a useful adjunct. The exact place of lamotrigine, which controls some myoclonia and makes them worse in other patients, requires further study. The findings are clearer when specific syndromes are considered. Valproate is the treatment of first choice for benign myoclonic epilepsy in infants, myoclonic astatic epilepsy, epilepsy with myoclonic absences, eyelid myoclonia with absences, juvenile myoclonic epilepsy and progressive myoclonus epilepsy. The addition of ethosuximide to valproate can be helpful to those with myoclonic absences, where this combination appears more beneficial than either valproate or ethosuximide alone and in eyelid myoclonia with absences. Lamotrigine can be effective therapy for juvenile myoclonic epilepsy and eyelid myoclonia with absences when used alone and, in conjunction with other antiepileptic drugs (AED) (usually valproate) for early myoclonic encephalopathy, myoclonic-astatic epilepsy and particularly, epilepsy with myoclonic absences. The myoclonia of infantile neuronal ceroid lipofuscinosis respond to lamotrigine. Severe myoclonic epilepsy of infants usually worsens with lamotrigine, but occasionally, children improve. Zonisamide added to clonazepam and valproate or a barbiturate, can reduce the cascade of myoclonia in progressive myoclonus epilepsies for at least 2 years, but relapse may occur thereafter.

Summary: Purpose: We studied falling manifestations of atonic epileptic drop attacks (AEDA) in 2 patients with cryptogenic epilepsy with myoclonic-astatic seizures. Methods: Using video-polygraphic examinations. For analysis, we recorded 51 seizures in 1 patient and 18 seizures in the other. The extent of AEDA ranged from collapsing and landing on the buttocks to head nodding only without falling. Results: Detailed video analysis of the drop attacks, with the patient in standing position, demonstrated the first manifestations to be flexion at the waist and knees, followed by further knee flexion, leading to falling straight down ~ and landing on the buttocks. Ictal polygraphs demonstrated diffuse interruptions of ongoing EMG dkcharges corresponding to the falls, indicating that these attacks are true atonic seizures. Conclusions: The falling manifestations of AEDA appeared to be characteristic and different from those of tonic drop seizures, which have been described as falling forward with tonic flexion of the hips, upper trunk, and head, as well as abduction or elevation of the arms. Key Words: Atonic epileptic drop attack-Generalized spike-and-wave complex-Myoclonic astatic seizures-Simultaneous video-EEG analysis.

The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy.

Objectives We studied epileptic drop attacks (EDA) in symptomatic epilepsy of early childhood by means of video-polygraphic recordings and compared clinico-electrical differences in EDA among patients with idiopathic myoclonic-astatic epilepsy (MAE). Subjects and methods Subjects consisted of 21 children with symptomatic epilepsy and 20 with idiopathic MAE whose EDA were documented at an age between 7 months and 6 years. The seizure types causing EDA as well as other demographic data were compared between the two epilepsy types. Results A video-polygraphic study captured a total of 188 EDA (median: 8) in patients with symptomatic epilepsy and 182 EDA (median: 7) in those with idiopathic MAE. In the former, EDA were caused by epileptic spasms (ES) corresponding to generalized biphasic slow discharges, sharp-and-slow wave complexes, or the flattening of ongoing background activity in 15 patients, atonic seizures associated with runs of generalized spike-and-wave complexes in four patients, and myoclonic-atonic seizures in the remaining two patients. The mode of occurrence of EDA in ES was periodic clustering in eight of 15 patients. Interictal EEG revealed generalized irregular multiple spikes-and-waves with focal or multifocal accentuations. Sixteen idiopathic MAE patients had myoclonic-atonic seizures while the remaining four had myoclonic-flexor seizures, all corresponding to generalized high amplitude spikes or polyspike-and-wave complexes and occurring singly. Conclusion EDA often seen in young children with symptomatic epilepsy were most frequently caused by flexor type ES and rarely by myoclonic-atonic seizures, a hallmark seizure type of MAE. In a clinical setting, the occurrence of periodic clusters and independent focal or multifocal accentuations of generalized spike-and-wave complexes in interictal EEG may indicate EDA caused by ES.

Background Myoclonic-astatic epilepsy (MAE) is an epileptic syndrome characterized by unique myoclonus, myoclonic-astatic, or astatic seizures in childhood. MAE prognosis vary from spontaneous remission to intractable seizures with profound mental retardation. Aim Identifying early risk factors may optimize the treatment of children with MAE. Our hypothesis is early onset age and focal spike discharges on EEG indicate a poor MAE prognosis. Methods Using the medical records of 9 children with MAE, we analyzed their clinical histories, EEG findings, and seizure symptoms. All patients were given follow-up observations/treatments by our department for at least 2 years after MAE onset. Results Five of the patients were given favorable prognoses because their seizures disappeared within 2 years of onset; the other 4 received poor prognoses because their seizures continued more than 2 years. MAE onset in patient with refractory seizures was earlier than that in those with a favorable prognosis (7-24 months vs. 23-38 months). All the patients with refractory seizures showed moderate or severe mental retardation. Among the 5 patients with good prognosis, EEGs showed two with focal spike discharges and three with only generalized spike discharges. In contrast, all cases with a poor prognosis had focal spike discharges. Conclusions MAE onset in patients with refractory seizures occurs earlier than in those with favorable prognosis. Prognosis was excellent when EEG findings show no focal spike discharges. Both early seizure onset and the focal spike discharges associated with MAE are indicators of poor prognosis.

Background: Myoclonic astatic epilepsy (MAE) is an idiopathic and generalized childhood epileptic syndrome. Although several studies have reported on cognitive function and intellectual outcome in MAE, little is known about the behavioral problems associated with this disease. The aim of this study was to clarify behavior and cognitive function in children with MAE. Methods: Four children who were diagnosed as having MAE using the proposed criteria of the International Classification of Epilepsies were retrospectively analyzed using patient records with regard to clinical and neuropsychological findings such as age of seizure onset, semiology and severity of seizures, treatment course, behavioral problems, EEG findings, and WISC-III and Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS) scores that indicate the tendency of autistic behaviors. Results: Disease onset in our cohort ranged from 9 to 35 months of age. Seizures were controlled within 3-8 months over a follow-up period of 4-12 years. All patients had borderline normal intelligence (mean IQ: 75.8 at 5-7 years of age) and exhibited impaired coordination, clumsiness, hyperactivity or impulsivity, and impaired social interaction after improvement of seizures. Though these autistic social problems manifested gradually, the children were able to adapt to school life with appropriate support. Interestingly, the behaviors of impaired social interaction and hyperactivity or impulsivity had already been observed before the onset of MAE in most patients, whose PARS scores were all higher than reference values (

Among nonsymptomatic epilepsies exhibiting several types of generalized seizures in children two syndromes were progressively identified: epilepsy with myoclonic-astatic seizures (MAE) and nonsymptomatic Lennox-Gastaut syndrome (LGS). Various approaches based on etiology, electroclinical semiology, and mathematical analysis have progressively helped to distinguish these two conditions. Both conditions preferentially affect boys. The course is stereotyped in MAE, characterized by progressive worsening of epilepsy, usual pharmacoresistance at onset and tonic-clonic seizures, myoclonus and frequent episodes of myoclonic status epilepticus. EEG shows 3Hz spike wave bursts characteristic of idiopathic generalized epilepsy together with slowing of the tracing. In LGS, major seizures are mainly atypical absences and tonic seizures with 0.5-2Hz slow spike-waves and eventually focal anomalies. Prognosis in both syndromes ranges from recovery without sequelae to pharmacoresistant epilepsy that has improved over the past 2 decades with the new generation antiepileptic compounds. Iatrogenic factors may contribute to the poor prognosis, mainly in MAE. Pathophysiology remains speculative for both syndromes: although both share factors of brain maturation, MAE is probably mainly related to genetic predisposition whereas LGS results from some unidentified cortical brain malformation. In unfavorable cases, there may therefore be a continuum between both syndromes. They need to be distinguished from other epilepsy syndromes and inborn errors of metabolism that begin in the same age range: atypical idiopathic benign epilepsy, frontal lobe epilepsy with secondary bisynchrony, ring chromosome 20, ceroid lipofuscinosis, and nonsymptomatic late-onset spasms.

Introduction We evaluated the long-term efficacy and tolerability of the orphan drug rufinamide (RUF) in children with pharmacoresistant myoclonic-astatic epilepsy (MAE, Doose syndrome). Methods This was a retrospective European multicenter study on eight patients who had started an intention-to-treat trial of RUF between July 2007 and June 2010. Clinical information was collected via questionnaire. Responder rate was defined as reduction of seizure frequency ≥50% in comparison to four weeks before starting RUF. Maximum follow-up was eighteen months. Results Responder rates were 7/8 patients after 3 months, 6/8 patients after 6 months and 5/8 patients after 12 months. RUF seemed particularly effective in the prevention of myoclonic-astatic seizures (comparable with drop attacks in Lennox-Gastaut-Syndrome, for which RUF is particularly effective). Some loss of efficacy was noticed in the long-term observation. Side-effects occurred in two patients. Seizure aggravation was not observed. Conclusion RUF seems to be a promising therapeutic option in children with MAE. Further studies are warranted to confirm these first observations.

Sturge-Weber syndrome is a neurocutaneous disorder classically characterized by the presence of facial port-wine stain and ipsilateral leptomeningeal angiomatosis. It is often associated with refractory epilepsy which requires surgical treatment. We present a case of a patient who initially presented with partial seizures of temporo-occipital origin, ipsilateral to the pial angiomatosis. During the course of the disease, the patient developed medically refractory epilepsy with partial seizures originating predominantly from the contralateral temporo-occipital area as well as myoclonic and myoclonic-astatic seizures. Resection of the occipital and temporal lobe affected by the pial angioma resulted in favourable outcome. Bilateral dysfunction observed in Sturge-Weber syndrome may result in an increased capability of focal discharges to generate synchronous epileptiform activity leading to an increased incidence of generalised seizures, most probably via a mechanism of secondary bilateral synchrony. [Published with video sequences].

ObjectiveTo determine if a significant proportion of patients with myoclonic-astatic epilepsy (MAE) have glucose transporter 1 (GLUT1) deficiency.DesignGenetic analysis.SettingAmbulatory and hospitalized care.PatientsEighty-four unrelated probands with MAE were phenotyped and SLC2A1 was sequenced and analyzed by multiplex ligation-dependent probe amplification. Any identified mutations were then screened in controls.Main Outcome MeasureAny SLC2A1 mutations.ResultsFour of 84 probands with MAE had a mutation of SLC2A1 on sequencing. Multiplex ligation-dependent probe amplification analysis did not reveal any genomic rearrangements in 75 of the remaining cases; 5 could not be tested. Two patients with MAE with SLC2A1 mutations also developed paroxysmal exertional dyskinesia in childhood.ConclusionsFive percent of our patients with MAE had SLC2A1 mutations, suggesting that patients with MAE should be tested for GLUT1 deficiency. Diagnosis of GLUT1 deficiency is a strong indication for early use of the ketogenic diet, which may substantially improve outcome of this severe disorder.

One of the most challenging areas in nosology is in the field of severe generalized epilepsy of early childhood. This is certainly true in the case of Lennox-Gastaut syndrome (LGS), an age-related epileptogenic encephalopathy which comprises several types of generalized seizures including tonic seizures, atypical absence seizures and frequent status epilepticus. EEG shows generalized slow spike waves, and as the disease progresses, cognitive functions deteriorate. LGS is listed in the 1989 classification of the International League Against Epilepsy alongside epilepsy with myoclonic astatic seizures and West's syndrome. A number of variants or atypical forms have been proposed. As a result, differential diagnosis presents a major challenge and includes specific generalized epilepsies, i.e., metabolic or inflammatory; secondarily generalized epilepsies, i.e., those arising from the frontal lobe; and severe forms of idiopathic generalized epilepsy, i.e., Doose syndrome. Antiepileptic drug (AED) treatment of LGS has been disappointing. Results obtained from anterior callosotomy have been promising, but only a small number of patients have been evaluated. Although the syndrome is rare, the severe nature and intractability of LGS emphasizes the need for the development of specific AEDs which would completely modify the quality of life for these patients.

Initiation of the ketogenic diet in a child with epilepsy and type 1 diabetes mellitus presents a challenge because the distinction between diet-induced ketosis and diabetic ketoacidosis is difficult to discern. We report the successful use of the ketogenic diet in a child with myoclonic astatic epilepsy and type 1 diabetes.