Idiopathic Focal Epilepsies In Childhood Research Articles

Self-limited epilepsy of childhood with affective seizures: A well-defined epileptic syndrome?

ObjectiveHere we present cases of focal epilepsy with affective symptoms analyzing seizure characteristics, EEG pattern, treatment, and outcome. MethodsA multicenter, descriptive, retrospective study was conducted evaluating 18 patients with self-limited epilepsy who presented with seizures with affective symptoms seen between April 2000 and April 2018 at eight Argentinian centers. ResultsEighteen patients had focal seizures with affective symptoms; all of them had affective symptoms characterized by sudden fright or terror and screaming. Seizures started with manifestations of sudden fright or terror manifested by a facial expression of fear; consciousness was mildly impaired in 15/18 patients.Eleven of the patients also had autonomic manifestations, such as pallor, sweating, and abdominal pain. In addition, four of these 11 patients had ictus emeticus and one also presented with unilateral deviation of the eyes and head.Speech arrest, salivation, glottal noises, and chewing or swallowing movements were observed in 2/18 patients at the onset of the affective seizures. Two others also had mild asymmetric dystonic seizures involving both hands and arms. Three patients had tonic deviation of the mouth involving the lips and tongue as well pharyngeal and laryngeal muscles, resulting in anarthria and drooling. Two patients had brief hemifacial focal clonic seizures. ConclusionAffective manifestations associated or not with motor and/or autonomic manifestations and associated with typical EEG features of the idiopathic focal epilepsies of childhood is a particular presentation of self-limited focal epilepsy in childhood.

Idiopathic focal epilepsies: the "lost tribe".

Idiopathic focal epilepsies: the "lost tribe".

Treatment of Classic Syndromes in Idiopathic Focal Epilepsies in Childhood

Of the classic syndromes of idiopathic (benign) focal epilepsies in childhood, more than half of children with Rolandic epilepsy and Panayiotopoulos syndrome do not need antiepileptic drug (AED) treatment. Monotherapy with carbamazepine, levetiracetam, sodium valproate, or clobazam is usually recommended for those with seizures that are unusually frequent (more than three), lengthy, distressing, or otherwise significantly interfering with the child's life. Other factors in favor of treatment include a short interval between the first three seizures, a younger age of onset (less than 4 years), or a presence of recurrent tonic–clonic seizures and diurnal seizures. In contrast to Rolandic epilepsy and Panayiotopoulos syndrome that may not need treatment, idiopathic childhood occipital epilepsy of Gastaut should be treated because seizures are frequent and secondarily generalized convulsions are probably unavoidable without medication. It is likely that all AEDs licensed as monotherapy for focal seizures and mainly carbamazepine and levetiracetam are suitable.The electroencephalogram does not predict prognosis or AED treatment needs, though there are views supporting that interictal spikes have an adverse effect on cognition.Strategies of withdrawing medication in idiopathic focal epilepsies in childhood differ among experts, although all agree that there is no need to continue medication 1 to 3 years after the last seizure, and certainly not after the age of 14 years, when most benign childhood focal seizures remit, or age 16, when they are practically nonexistent.In the acute stage of status epilepticus, control of the seizures is of paramount importance. Convulsive status epilepticus is a life threatening condition and should be terminated as soon as possible. Autonomic status epilepticus needs thorough evaluation for proper diagnosis and management. Benzodiazepines, intravenously, in rectal or buccal preparations are commonly used to terminate long lasting seizures and status epilepticus. Early parental treatment is more effective than late emergency treatment. Buccal midazolam is probably the first choice medication for out-of-hospital termination of status epilepticus.Parental education and psychological support are the cornerstone of the optimal management because despite excellent prognosis, idiopathic focal epilepsies in childhood usually have a dramatic impact to parents.

Treatment of Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

The relationship between continuous spike-and-wave discharges during slow sleep (CSWSS) and neuropsychological impairment (cognitive functions, memory consolidation, and language and behavior disturbances) has been clearly demonstrated. These phenomena occur not only in symptomatic cases of CSWSS or electrical status epilepticus in sleep (ESES) syndrome, but also in the different conditions that constitute the spectrum of atypical evolutions of idiopathic focal epilepsies of childhood (IFEC). In spite of continuous advances in treatment, management is still difficult and challenging. Treatment options of atypical evolutions of IFEC include benzodiazepines, sulthiame, levetiracetam, valproic acid, and ethosuximide. Other drugs such as lacosamide and acetazolamide have been proposed. Usual antiepileptic drugs such as carbamazepine, phenobarbital, phenytoin, oxcarbazepine, lamotrigine, and topiramate were proven to be capable of inducing ESES. Steroids and intravenous immunoglobulins were recommended in refractory cases. Surgery, ketogenic diet, and vagal nerve stimulation were also used in some cases. Our interest regarding a scheme of treatment in atypical evolutions of IFEC is centered on two questions: (1) Is it possible to prevent the evolution of IFEC into atypical focal epilepsies of childhood, status epilepticus of IFEC, Landau–Kleffner's syndrome, or ESES syndrome? (2) Which is the treatment of choice once one of these conditions is installed?

Genetics Studies in Idiopathic Focal Epilepsies in Childhood

Numerous “epilepsy genes” have been identified in the recent years, thanks to the recent progress in massive parallel sequencing and genome analysis. Among the formerly called “idiopathic” childhood focal epilepsies, a first and major gene responsible for focal epilepsies and epileptic encephalopathies with speech and language dysfunction (the epilepsy–aphasia spectrum, EAS), GRIN2A, has been identified. GRIN2A encodes the GluN2A subunit of N-methyl-D-aspartate receptors, which are gated by the excitatory neurotransmitter glutamate. More than 60 mutations of various types and with various functional consequences in vitro have been reported. Several rare genetic variants that may influence EAS have been reported in a few other genes. The identification of GRIN2A as a first cause of EAS represents a first key point that will help in deciphering the underlying pathophysiology and in understanding the clinical heterogeneity and variability seen in the patients and families.

Physiopathology of Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

This article aims to discuss if the underlying etiology is an important determinant of atypical evolution of idiopathic focal epilepsy (IFE) in childhood and if there might be biomarkers that would predict atypical evolution. It appears that the determinants of atypical evolution remain largely unknown but that both genetic and epigenetic factors are likely to be involved. The analysis of scalp electroencephalography remains the best biomarker of atypical evolution. However, functional neuroimaging methods of investigation are helpful to better understand how epileptic activity affects brain functioning at rest and during goal-directed tasks and to delineate the extent of brain networks that are impaired by epileptic activity. Moreover, neuroimaging bring new arguments favoring the idea that typical and atypical IFE should not be viewed as distinct entities but as a unique syndrome with various degrees of severity that should be treated using tailored strategies and robust biomarkers of efficacy.

Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

Clinical and electroencephalographic (EEG) features of the three well-defined idiopathic focal epilepsies in childhood (IFEC)—benign childhood epilepsy with centrotemporal spikes (BCECTS), Panayiotopoulos syndrome, and the Gastaut type of idiopathic occipital epilepsy of childhood (IOEC-G)—have been clearly described and reported. It is also known that a significant percentage of children with IFEC present what were named atypical features in seizures and EEG abnormalities. We are studying here the small number of patients with IFEC who not only present atypical features, but also evolve into the spectrum of epileptic encephalopathies related with continuous spike-and-wave during sleep (CSWSS) or electrical status epilepticus during sleep (ESES), which includes atypical benign focal epilepsy of childhood, status of BCECTS, Landau-Kleffner syndrome, and CSWSS or ESES syndrome. We also emphasize that some patients with these encephalopathic course of IFEC present a mix or a sequence in time of the four mentioned subsyndromes.

Clinical and EEG Features of Idiopathic Focal Epilepsies in Childhood

The International League Against Epilepsy (ILAE) report lists three well-defined syndromes of idiopathic focal epilepsies in childhood: benign childhood epilepsy with centrotemporal spikes (BCECTS), Panayiotopoulos syndrome (PS), and idiopathic childhood occipital epilepsy of Gastaut (ICOE-G). The concept of idiopathic and benign focal epilepsies in childhood is relevant as the term implies absence of structural brain lesions and genetic predisposition in the presence of age-dependent seizures. BCECTS is the most frequent of the benign focal epilepsies in childhood accounting for 15 to 25% of epilepsy syndromes in children below 15 years of age. It is also the most frequent epilepsy syndrome occurring at school age. The prevalence of PS was around 13% in children aged 3 to 6 years with one or more nonfebrile seizures, and 6% in the age group of 1 to 15 years. These figures may be higher if children who are currently considered to have an atypical clinical presentation are included in the syndrome. PS is the most common specific cause of nonfebrile status epilepticus in childhood. ICOE “Gastaut type” is a rare manifestation of a focal idiopathic epilepsy that has an age-related onset and is often age limited. The seizures of ICOE Gastaut type are always of occipital-lobe onset and primarily manifest with visual seizures, which are the most typical and usually the first ictal symptom, but other types of seizures may be associated. ICOE “Gastaut type” is a rare condition with a probable prevalence of 0.2 to 0.9% of all epilepsies, and accounting for 2 to 7% of benign childhood focal seizures.The recognition of these age-dependent epileptic syndromes is crucial for the adequate management of the children and their family.

Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

Impaired sleep-related consolidation of declarative memories in idiopathic focal epilepsies of childhood

ObjectiveDeclarative memory is consolidated during sleep in healthy children. We tested the hypothesis that consolidation processes are impaired in idiopathic focal epilepsies (IFE) of childhood in association with frequent interictal epileptiform discharges (IEDs) during sleep. MethodsA verbal (word-pair association) and a nonverbal (2D object location) declarative memory task were administrated to 15 children with IFEs and 8 control children 6–12years of age. Patients had either centrotemporal (11 patients) or occipital (4 patients) IEDs. All but 3 patients had a history of unprovoked seizures, and 6 of them were treated with valproate (VPA). The learning procedure (location of object pairs presented on a grid; association of word pairs) was executed in the evening. Retrieval was tested immediately after learning and on the next morning after a night of sleep. Participants were tested twice, once in natural home conditions and one month later in the unfamiliar conditions of the sleep unit under EEG monitoring. ResultsOvernight recall performance was lower in children with IFE than in control children on both tasks (ps<0.05). Performance in home conditions was similar to that in hospital conditions. Higher spike–wave index (SWI) during nonrapid eye movement (NREM) sleep was associated with poorer performance in the nonverbal task (p<0.05). Valproate treatment was not associated with overnight recall performance for both tasks (ps>0.05). ConclusionMemory consolidation is impaired in IFE of childhood. The association between higher SWI during NREM sleep and poorer nonverbal declarative memory consolidation supports the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation.

EEG‐fMRI in atypical benign partial epilepsy

Atypical benign partial epilepsy (ABPE) is a subgroup among the idiopathic focal epilepsies of childhood. Aim of this study was to investigate neuronal networks underlying ABPE and compare the results with previous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies of related epilepsy syndromes. Ten patients with ABPE underwent simultaneous EEG-fMRI recording. In all 10 patients several types of interictal epileptiform discharges (IEDs) were recorded. Individual IED-associated blood oxygen level-dependent (BOLD) signal changes were analyzed in a single subject analysis for each IED type (33 studies). A group analysis was also performed to determine common BOLD signal changes across the patients. IED-associated BOLD signal changes were found in 31 studies. Focal BOLD signal changes concordant with the spike field (21 studies) and distant cortical and subcortical BOLD signal changes (31 studies) were detected. The group analysis revealed a thalamic activation. This study demonstrated that ABPE is characterized by patterns similar to studies in rolandic epilepsy (focal BOLD signal changes in the spike field) as well as patterns observed in continuous spikes and waves during slow sleep (CSWS) (distant BOLD signal changes in cortical and subcortical structures), thereby underscoring that idiopathic focal epilepsies of childhood form a spectrum of overlapping syndromes.

Electroencephalographic generalized features in idiopathic childhood focal epilepsies

Purpose Idiopathic focal epilepsies in childhood including benign childhood epilepsy with occipital paroxysms (BEOP) or benign childhood epilepsy with centro-temporal spikes (BCECTS) are characterized by specific focal electrographic patterns as the name indicates. Generalized spike-wave discharges in children with idiopathic focal epilepsy can suggest a neurobiological continuum with the idiopathic generalized epilepsies. We assessed the prevalence of generalized epileptiform discharges and generalized seizures in BEOP/BCECTS patients. Methods Between August 2005 and November 2008, we identified 220 cases with electroclinical features typical of idiopathic focal epilepsies, 172 patients with BCECTS and 48 patients with BEOP, excluding patients whose neurological examinations or brain MRI were abnormal. We analyzed gender, age at onset, manifestation of generalized seizures, and serial EEG records to detect generalized abnormalities. Results Of our population, 42 patients (19.1%, 22 boys), 30 (17.4%) of 172 BCECTS patients and 12 (25.0%) of 48 BEOP patients, showed generalized spike-wave discharges once or more during follow-up. The typical 3-Hz generalized spike wave discharge was noticed in 7 patients and concurrence with clinical generalized seizure was observed in 11. Conclusion A relatively high incidence of generalized spike-wave discharge and concurrence with generalized seizure were observed in patients with BEOP/BCECTS, with the incidence being higher in BEOP patients than in those with BCECTS. It may be inferred that idiopathic focal epilepsy is not a fixed syndrome but is a part of a broad, age-related, benign, seizure susceptibility syndrome.

Levetiracetam as add-on therapy in different subgroups of “benign” idiopathic focal epilepsies in childhood

Several recent studies have shown that levetiracetam (LEV) can be beneficial in the treatment of children with typical rolandic epilepsy (RE). Reports about the effectiveness of LEV in the treatment of children with the less benign variants in the spectrum of “benign” idiopathic focal epilepsies are still rare. Little is known about the effect of LEV on interictal epileptiform discharges in these syndromes. We report on LEV therapy in 32 children (mean age: 10.6 years, range: 4–14) with RE or variants like atypical benign idiopathic partial epilepsy of childhood (ABIPEC), Landau–Kleffner syndrome (LKS), and continuous spikes and waves during sleep (CSWS) and in children with benign idiopathic focal epileptiform discharges of childhood (BIFEDC). Cognitive and behavioral problems, not seizures, may be related to the pathological EEG. Patients with a reduction in seizure frequency >50% and/or reduction in BIFEDC >90% 3 months after having started LEV therapy were defined as responders. The average dose of LEV was 39 mg/kg body wt per day; LEV was given in monotherapy to 31.3% of the patients. Overall, 20 of 32 patients (62.5%) did benefit: 12 of 24 patients had a >50% reduction in seizure frequency; 2 of 24 patients (8.3%) were completely seizure free; 18 of 32 patients (56.3%) had a >90% reduction in BIFEDC (including CSWS); 6 of 32 (18.8%) had an EEG completely free of epileptiform discharges; and 17 of 32 (53.1%) showed improvement in cognition and/or language functions and/or behavior. Surprisingly, LEV tended to be more helpful in atypical rolandic epilepsies and other variants.

Childhood occipital epilepsy of Gastaut: A study of 33 patients

To characterize the electroclinical features and evolution of childhood occipital epilepsy of Gastaut (COE-G). Children with electroclinical criteria of COE-G were retrospectively identified and followed-up clinically, and with sleep and awake EEGs between 1990 and 2007. We identified 33 patients with COE-G. In the same length of time, 201 children with Panayiotopoulos syndrome and 410 children with benign childhood epilepsy with centrotemporal spikes were registered. COE-G had a peak age at onset of 8.5 years. Visual manifestations were the most common ictal event. Ictal deviation of the eyes was frequent. Approximately half of the patients had migraine-like symptoms. In all patients the seizures occurred while awake, and 11 also had seizures during sleep. The majority of the patients had occipital spike-wave discharges when the eyes were closed that disappeared or attenuated when the eyes were opened. Prognosis was excellent in 80% of the cases. This study confirms the existence of COE-G, a rare but well-defined syndrome within the group of idiopathic focal epilepsies in childhood.

Autonomic Symptoms during Childhood Partial Epileptic Seizures

To the Editors: I read with great interest the paper by Fogarasi and colleagues (Fogarasi et al., 2006) about autonomic symptoms and signs (AS/S) during partial epileptic seizures in 100 children with symptomatic focal epilepsies evaluated with video-EEG telemetry. It provides valuable information on an area we know too little about, and bridges the gap between symptomatic focal epilepsies in adults and idiopathic focal epilepsies of childhood, such as Panayiotopoulos syndrome (PS) (Ferrie et al., 2006) and others. Comparison of the relevant data would help understand not only if and how autonomic ictal semiology in symptomatic focal epilepsies may evolve with age, but also the relationship between symptomatic and idiopathic epileptogenesis in children. Data on adults come mainly from series of surgical candidates (Kramer et al., 1988; Devinski et al., 1995; Schauble et al., 2002). Here, ictal AS/S (mainly gastrointestinal, such as vomiting and hypersalivation) are rare, usually indicate involvement of the non-dominant temporal lobe, and tend to occur late in the seizure sequence during the phase of unresponsiveness of the complex partial seizure. On the other end, in idiopathic focal epileptogenesis with prominent autonomic seizures (PS) ictal AS/S occur as a rule early – frequently from onset – and in clear consciousness, and either persist as the sole ictal manifestations (purely autonomic seizures), or give way to more conventional seizure semeiology such as eye deviation, hemiconvulsions or rarely visual symptoms late in seizure sequence. Here seizures are prolonged and autonomic symptoms are usually multiple per seizure, with ictal vomiting occurring in up to 75% of children (Ferrie et al., 2006). Fogarasi and his colleagues report that at least one autonomic symptom was noted in 60 children (most with temporal lobe epilepsy); each child had no to three AS (median one), and only epigastric aura and postictal coughing (postictal symptoms were also included) localised to the temporal lobe; no AS/S lateralised the ictal onset zone. Interestingly, only 5 of the 60 children (8.3%) with AS/S during their seizures had vomiting, no child had both epigastric aura and vomiting, and papillary changes, cyanosis or pallor were either exceptional or were not observed at all. This paper describes information of extreme practical-clinical and theoretical significance. One can appreciate that a picture of ictal AS/S across different ages, syndromes and aetiologies is gradually coming into focus, and rightly one would like to learn more on autonomic semeiology in this – admittedly specific from the nosological aspect (all with medically intractable focal epilepsies) – group of children. The authors might wish to expand as much as this might be possible a posteriori on relevant points that are not easily deductible from the original paper. First, on the relative power and the timing of the AS/S within the ictal semeiology of the individual seizures, it is not clear whether AS/S were the quantitatively most predominant or clinically most important ictal manifestations in any of the children or they merely coexisted with conventional motor or sensory phenomena. It may also be interesting to know if AS/S and in particular ictal vomiting occurred early in the seizure sequence as in children with idiopathic autonomic seizures or late during the phase of unresponsiveness as in adults. Second, on seizure duration it would be interesting to know if focal seizures with autonomic symptoms lasted longer than those without and what was a typical length, and also whether the authors record or obtain historical evidence of partial status epilepticus with predominantly autonomic ymptoms. Third, did they observe or obtain historical evidence of episodes of sudden loss of muscle tone and awareness during the seizures, a phenomenon that has been reported (Ferrie et al., 2006) and recorded (Oguni et al., 1999) in children with PS.

Oxcarbazepine and atypical evolution of benign idiopathic focal epilepsy of childhood

Patients that have benign epilepsy with centrotemporal spikes (BECTS) may occasionally experience an atypical development in their course when treated with drugs such as carbamazepine. Three patients with electroclinical patterns consistent with BECTS showed seizure exacerbation during oxacarbazepine (OXC) therapy. Two manifested atypical absences, neuropsychological disturbances, and generalized spike-and-wave discharges in their electroencephalograms (EEGs) that became continuous during sleep. The third patient showed, during OXC therapy, more frequent partial motor seizures which ended with ictal vomiting and post-ictal obnubilation. EEGs recorded during sleep showed discontinuous paroxysmal activity in the right centrotemporal area. Symptoms were reversed following discontinuation of the OXC therapy. Although electroclinical findings were consistent with a BECTS diagnosis, all patients had some atypical features. Our observations show that BECTS patients, in particular those presenting with atypical findings, might be at risk for developing paradoxical reactions to OXC therapy. We suggest that OXC should be included in the list of drugs that may cause electroclinical deterioration in these patients.

Preface

This supplement contains the abstracts of the 37th Congress of the Japan Epilepsy Society held at Sendai International Center in Sendai on October 30 and 31, 2003. Epileptology is an interdisciplinary field consisting of neuropsychiatry, pediatric neurology, neurosurgery, and basic neurosciences. Recent advances in basic neuroscience and molecular biology have clarified previously mysterious mechanisms of neuronal excitation and inhibition. Various techniques for examining brain function also promote the progress of epileptology. The main theme of this meeting was “To control epilepsy: From the newest knowledge toward total care of epilepsy patients.” The theme implies that epileptologists should strive to apply the progress of scientific results to the control of epilepsy in clinical practice, which is the final goal for patients with epilepsy and their families. The scientific program consisted of two invited special lectures; “PET localization of the epileptic focus” by Professor Harry T. Chugani from Detroit, and “Idiopathic focal epilepsies of childhood: Rolandic, Panayiotopoulos syndrome, and others,” by Professor Koutroumanidis from London. The program presented two symposia: “New techniques of functional neuroimaging and epilepsy” and “Comprehensive treatment and care of epilepsy.” One workshop focused on “Driving licenses for people with epilepsy after the amendment of the Road Traffic Act.” In total, 163 free papers were presented, including five papers categorized as neuroscience studies in epilepsy. This special supplement of Epilepsia contains 59 selected free papers, including five neuroscience studies. My impression of this meeting was that it was quite successful and could contribute to the progress of epileptology and help to establish comprehensive care for patients with epilepsy and their families. I express my great appreciation to members of the Program Committee and Local Organizing Committee, lecturers, speakers, and chairs, all of whom contributed to the success of the meeting.

Early dissociation of verbal and nonverbal gestural ability in an epileptic deaf child

Studies of sign language aphasia in deaf adults have provided the evidence for two separable verbal and nonverbal manual gesture systems. We report a congenitally deaf child with a idiopathic focal epilepsy of childhood who showed specific language impairment in French sign language. The child's amazing performances in miming or sketching pictures she was unable to sign support the notion of an early dissociation of the two gestural systems.

Early dissociation of verbal and nonverbal gestural ability in an epileptic deaf child

Studies of sign language aphasia in deaf adults have provided the evidence for two separable verbal and nonverbal manual gesture systems. We report a congenitally deaf child with a idiopathic focal epilepsy of childhood who showed specific language impairment in French sign language. The child's amazing performances in miming or sketching pictures she was unable to sign support the notion of an early dissociation of the two gestural systems.