PURPOSE:

To retrospectively analyze the electroclinical features, etiology, treatment, and prognosis of 21 patients with encephalopathy with hemi-status epilepticus during sleep (ESES) or hemi-continuous spikes and waves during slow sleep (CSWSS) syndrome.

METHODS:

Charts of 21 patients with hemi-ESES/CSWSS syndrome followed between 1997 and 2012 were analyzed. Inclusion criteria were: (1) Focal seizures or apparently generalized seizures and focal EEG epileptiform discharges; (2) Further occurrence of atypical absences, and myoclonic, atonic, and/or generalized seizures; (3) Cognitive impairment and/or behavioral disturbances; (4) Hemi-continuous spike-and-wave discharges during slow sleep in more than 85% of non-REM sleep at onset and throughout the ESES/CSWSS period.

RESULTS:

Mean follow-up from onset of hemi-ESES/CSWSS was 8 years (range, 2-15 years). Idiopathic cases were not identified. Unilateral polymicrogyria was found in 11, shunted hydrocephalus in four, a porencephalic cyst associated with polymicrogyria in three, and a thalamic lesion in three children. All started with focal seizures with or without secondary generalization. During the hemi-ESES/CSWSS period, all children developed new types of seizure, such as negative and positive myoclonus, absences, motor deterioration, cognitive impairment, and behavioral disturbances. All AED responders returned to baseline cognitive development. Seven patients were refractory to AEDs.

CONCLUSION:

Our study suggests that the hemi-ESES/CSWSS syndrome has electroclinical features compatible with an epileptic encephalopathy. The most commonly used treatments were clobazam, ethosuximide, and sulthiame, alone or in combination. In refractory cases, high-dose corticosteroids were administered. Although the number of patients in this study is too low to draw definite conclusions, we consider that in children with hemi-ESES/CSWSS secondary to a unilateral lesion, surgery should be considered.

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.

Severe myoclonic epilepsy in infancy (SMEI) is a rare disease, characterized by febrile and afebrile, generalized and unilateral, clonic or tonic-clonic seizures that occur in the first year of life in an otherwise apparently normal infant. They are later associated with myoclonus, atypical absences, and partial seizures. Developmental delay becomes apparent within the second year of life and is followed by definite cognitive impairment and personality disorders of variable intensity. In the borderline form, children do not present with myoclonic symptoms but have the same general picture. SMEI is a channelopathy and the genetic studies have shown a mutation in the SCN1A gene in 70 to 80% of the patients, including the borderline forms. At present, there are no well-established correlations between genotype and phenotype. The electroencephalograms, often normal at the onset, display both generalized and focal anomalies, without a specific electroencephalographic pattern. As a rule, neuroimaging is normal. All seizure types are resistant to antiepileptic drugs and status epilepticus is frequent. Some drugs have been shown to aggravate the seizures and must be avoided. Two recent drugs have been proved to partially control the convulsive seizures and the status epilepticus. Therefore, it is crucial to diagnose this epilepsy soon after its onset in order to prescribe the most appropriate treatment.

Angelman syndrome combines severe mental retardation, epilepsy, ataxia, speech impairment, and unique behavior with happy demeanor, laughing, short attention span, hyperactivity, and sleep disturbance. Occurrence has been calculated at 1:20000 to 1:12000 constituting about 6% of all children with severe mental retardation and epilepsy. The physical "prototype" includes microcephaly with flat neck, fair skin and hair, wide-spaced teeth, and open mouth with tongue protrusion. Epilepsy is characterized by atypical absences, erratic myoclonus, and occasional tonic-clonic seizures. EEG demonstrates high-amplitude 2-3Hz delta activity with spike and slow-wave discharges and sleep-activated generalized epileptiform discharges. Sodium valproate, benzodiazepines, and priacetam are frequently used and effective. Development is generally slow, the majority attaining independent walking in the first 2.5-6 years. Vocabulary is limited to a few single words with superior speech and object apprehension. The condition is due to a lack of expression of the UBE3A gene on chromosome 15q. Maternal deletions of 15q11-13 produce the most pronounced phenotype (65-70% of probands), uniparental disomy and imprinting center mutations (10%), and UBE3A point mutations (11%) produce milder phenotypes.

PURPOSE:

To retrospectively analyze the electroclinical features, etiology, treatment and prognosis of 117 patients with encephalopathy with status epilepticus during sleep (ESES) or continuous spike and waves slow sleep (CSWSS) syndrome with a long-term follow-up.

METHODS:

Charts of 117 patients with ESES/CSWSS syndrome followed between 1990 and 2012 were analyzed. Inclusion criteria were: (1) focal seizures or apparently generalized seizures and focal EEG epileptiform discharges; (2) further occurrence of atypical absences, and myoclonic, atonic, and/or generalized seizures; (3) cognitive impairment and/or behavior disturbances; (4) continuous spike-and-wave discharges during slow sleep in more than 85% of non-REM sleep. Patients with spike-and-wave discharges in less than 85% of slow sleep were also analyzed. KEY

FINDINGS:

'Mean follow-up from onset of ESES/CSWSS was 13 years (range, 2-22 years) in the symptomatic/structural and non-idiopathic group consisting of 79 children and 10.5 years (range, 2-21 years) in the idiopathic group consisting of 38 children. The comparison of clinical findings and localization of paroxysmal EEG abnormalities (focal, multifocal, or generalized) at the different stages (before, during, and after ESES/CSWSS) and the percentage of spike-wave index during ESES/CSWSS between the symptomatic/structural and non-idiopathic and the idiopathic group was not statistically significant.

SIGNIFICANCE:

ESES/CSWSS syndrome is an epileptic encephalopathy with similar electroclinical findings in children with a >85% spike-wave index and those with a <85% spike-wave index. In this series of patients, the most commonly used treatments were clobazam, ethosuximide, sulthiame, alone or in combination. In refractory cases, high-dose steroids were administered. Among the AED responders, the idiopathic cases returned to normality and the structural cases returned to baseline cognitive development.

There is currently no resective (potentially curative) surgical option that is useful in patients with Lennox-Gastaut syndrome. Palliative procedures such as callosotomy (Cx), vagus nerve stimulation (VNS) or deep brain stimulation have been offered. We compared the outcomes after Cx or VNS in two consecutive prospective cohorts of patients with generalised epilepsy.Twenty-four patients underwent callosotomy from 2006 to 2007 (Group 1); 20 additional patients were submitted to VNS from 2008 to 2009 (Group 2). They had generalised epilepsy of the Lennox-Gastaut or Lennox-like type. They were submitted to a neurological interview and examination, interictal and ictal video-EEG, high resolution 1.5T MRI, and cognitive and quality of life evaluations. The two-year post-operative follow-up results were evaluated for each patient.The final mean stimuli intensity was 3.0mA in the Group 2 patients. Seizure-free patients accounted for 10% in Group 1 and none in Group 2. Ten and sixteen percent of the Group 1 and 2 patients, respectively, were non-responders. Improvements in attention and quality of life were noted in 85% of both Group 1 and 2 patients. Rupture of the secondary bilateral synchrony was noted in 85% of Group 1 patients; there was no EEG modification after VNS in Group 2. Both procedures were effective regarding the control of atypical absences and generalised tonic-clonic seizures. Both procedures were not effective in controlling tonic seizures. Callosotomy was very effective in reducing the frequency of atonic seizures, but VNS was ineffective. In contrast, callosotomy was not effective in reducing myoclonic seizures, whereas VNS was.Callosotomy might be preferred as the primary treatment in children with Lennox-Gastaut syndrome, and no specific findings on MRI if atonic seizures prevail in the patient's clinical picture; when myoclonic seizures prevail, the same might hold true in favour of VNS. When atypical absence or generalised tonic-clonic seizures are the main concern, although both procedures carry similar effectiveness, VNS might be considered a good option as an initial approach, taking into account the adverse event profile. Patients should be advised that both procedures are not very effective in the treatment of tonic seizures.

Rationale:

Atypical benign partial epilepsy (ABPE) is characterized by centro-temporal electroencephalography (EEG) spikes, continuous spike and waves during sleep (CSWS), and multiple seizure types including epileptic negative myoclonus (ENM), but not tonic seizures. This study evaluated the localization of magnetoencephalography (MEG) spike sources (MEGSSs) to investigate the clinical features and mechanism underlying ABPE.

Methods:

We retrospectively analyzed seizure profiles, scalp video EEG (VEEG) and MEG in ABPE patients.

Results:

Eighteen ABPE patients were identified (nine girls and nine boys). Seizure onset ranged from 1.3 to 8.8years (median, 2.9years). Initial seizures consisted of focal motor seizures (15 patients) and absences/atypical absences (3). Seventeen patients had multiple seizure types including drop attacks (16), focal motor seizures (16), ENM (14), absences/atypical absences (11) and focal myoclonic seizures (10). VEEG showed centro-temporal spikes and CSWS in all patients. Magnetic resonance imaging (MRI) was reported as normal in all patients. MEGSSs were localized over the following regions: both Rolandic and sylvian (8), peri-sylvian (5), peri-Rolandic (4), parieto-occipital (1), bilateral (10) and unilateral (8). All patients were on more than two antiepileptic medications. ENM and absences/atypical absences were controlled in 14 patients treated with adjunctive ethosuximide.

Conclusion:

MEG localized the source of centro-temporal spikes and CSWS in the Rolandic-sylvian regions. Centro-temporal spikes, Rolandic-sylvian spike sources and focal motor seizures are evidence that ABPE presents with Rolandic-sylvian onset seizures. ABPE is therefore a unique, age-related and localization-related epilepsy with a Rolandic-sylvian epileptic focus plus possible thalamo-cortical epileptic networks in the developing brain of children.

The study included 1261 patients with different forms of epilepsy. Ages at onset of disease varied from the first days of life to 18 years old. Absence seizures were identified in 231 (18.3%) patients, atypical absences (AA) in 129 (10.2%) of patients, with the frequency of absence seizures 55.8% in the total group. Patients with AA had different forms of epilepsy with the prevalence of cryptogenic/symptomatic forms with the phenomenon of secondary bilateral synchronization in the EEG. If epilepsy manifested itself at the age above 12 years old, AA were not noted. The study demonstrated the relevance of using video-EEG monitoring for diagnosis of epilepsy with AA. The antiepileptic treatment was effective in 53.5% of patients.

Dravet syndrome is a severe, genetic epileptic encephalopathy with seizures starting during the first year of life. We present a review of the genetic and clinical picture along with treatment aspects.This review is based on a non-systematic literature search in PubMed until April 2011 and the personal experiences of the authors.Dravet syndrome should be suspected in children with febrile hemiconvulsions or tonic-clonic seizures in the first year of life. Non-febrile seizures also occur, and other seizure types gradually appear, e.g. myoclonic jerks, atypical absences or focal seizures. In adulthood the clinical picture is less characteristic. The clinical diagnosis is supported by genetic testing; 70-80% of the patients have mutations in the sodium channel subunit gene SCN1A. Seizure control is difficult to achieve, but valproate, benzodiazepines and stiripentol may cause improvement, whereas sodium channel blockers, such as lamotrigine and carbamazepine may aggravate the tendency towards seizures.Dravet syndrome appears to be an under-recognised condition among both children and adults with severe epilepsy and learning disability. Clinical information from the first years of life is essential in making the diagnosis. A correct diagnosis at an early age is essential for appropriate treatment and genetic counselling.

To summarize the electroclinical characteristics of myoclonic atonic epilepsy (MAE) in children.The clinical data, video electroencephalogram (EEG) and simultaneous electromyography (EMG) of MAE patients were analyzed. The treatment and its effects were followed up.In 47 MAE patients, 25 had a history of febrile seizures (FS), 20 had a family history of FS or epilepsy. All patients had a normal development before the illness. The age of afebrile seizure onset was between 1.4 years to 5.8 years. The first seizure was generalized tonic-clonic seizure (GTCS) in 41 patients (87.2%). All patients had multiple seizure types, including 47 GTCS (97.9%), 34 myoclonic atonic seizures (72.3%), 47 myoclonic seizures (100%), 32 atonic seizures (68.1%), 36 atypical absences (76.6%) and 3 tonic seizures (6.4%). EEG backgrounds were slow or parietal θ rhythm, interictal EEG showed 1-4 Hz (predominant 2-3 Hz) generalized spike and wave or poly spike and wave discharges in all cases. Seizures were controlled by antiepileptic drugs (AEDs) in 41 patients (87.2%). Valproate was used in 37. Lamotrigine was used in 26. Mild mental retardation was observed in 10 children after the onset of the illness.The clinical features of MAE included the following: the development was normal before the onset of the illness; the onset of seizure type was often GTCS. All patients had multiple generalized seizure types. Myoclonic atonic seizure was its characteristic seizure type. EEG showed generalized discharges. Early diagnosis and rational choice of AEDs are important for getting a better prognosis.