Is sleep-related consolidation impaired in focal idiopathic epilepsies of childhood? A pilot study

We investigated sleep-related declarative memory consolidation in four children with focal idiopathic epilepsy. In a population of healthy control children, recall of learned pairs of words was increased after a night of sleep, but not after a daytime wakefulness period. In children with epilepsy (1 case of benign epilepsy with centro-temporal spikes, 1 case of benign childhood epilepsy with occipital paroxysms, and 2 cases of epileptic encephalopathy (EE) with continuous spike and waves during slow-wave sleep, CSWS), recall performance significantly decreased overnight, suggesting impairment in sleep-related declarative memory consolidation. Hydrocortisone treatment in one patient with EE with CSWS resulted in normalization of the sleep EEG together with normalization of overnight memory performance, which was not the case in the other EE/CSWS patient whose sleep EEG was only partially improved. These preliminary results suggest that interictal epileptiform discharges in idiopathic focal epilepsies may disrupt the brain processes underlying sleep-related memory consolidation.     

High‐frequency oscillations in idiopathic partial epilepsy of childhood

Purpose: We explored high‐frequency oscillations (HFOs) in scalp sleep electroencephalography (EEG) studies of patients with idiopathic partial epilepsy (IPE) of childhood in order to obtain a better understanding of the pathologic mechanisms underlying IPE. Methods: The subjects were 45 patients, including 32 with benign childhood epilepsy with centrotemporal spikes (BCECTS) and 13 with Panayiotopoulos syndrome (PS). A total of 136 EEG records were investigated through temporal expansion and filtering of traces and time‐frequency spectral analysis. Key Findings: HFOs with frequency of 93.8–152.3 Hz (mean 126.2 ± 13.6 Hz) in the band of ripples were detected in association with spikes in 97 records (71.3%). Time from last seizure to the EEG recording was significantly shorter in those with spike‐related HFOs than in the EEG recordings with spikes without HFOs (p = 0.006). Although time from last seizure reflects age, age at the time of recording was not significantly different between EEG studies with and without HFOs. Peak‐power values of the high‐frequency spots in time‐frequency spectra were significantly negatively correlated with time from last seizure (R² = 0.122, p < 0.001) but not with age at the time of recording. Peak frequencies of the high‐frequency spectral spots were not significantly correlated with age at the time of recording or with time from last seizure. Significance: The close relationship between the generation of spike‐related HFOs and the period of active seizure occurrence indicated that HFOs may tell us more about epileptogenicity in IPE than the spikes themselves. Because there is a spectrum of pediatric epileptic disorders extending from the benign end of BCECTS to the encephalopathic end of epilepsy with continuous spike‐waves during slow‐wave sleep (CSWS), and HFOs that have already been detected in association with CSWS were more prominent than HFOs in IPE, intense spike‐related HFOs may indicate poor prognosis.     

Encephalopathy related to status epilepticus during slow sleep (ESES) as atypical evolution of Panayiotopoulos syndrome: an EEG and neuropsychological study

Aim: We report two patients with Panayiotopoulos syndrome (PS) who developed encephalopathy related to status epilepticus during slow sleep (ESES) at the peak of their clinical course. Methods: Clinical charts and EEG data were reviewed. Results: The patients exhibited nocturnal autonomic seizures and occipital EEG foci, the latter of which later evolved into multifocal EEG foci with synchronous frontopolar and occipital spikes (Fp‐O EEG foci), and finally into continuous spikes‐waves during sleep (CSWS; spike‐wave index >85% based on whole‐night sleep recording) at eight years and seven years of age, respectively. The occipital spikes always preceded frontopolar spikes by 30～50 mseconds based on the analysis of CSWS. Neuropsychological ability, including IQ, deteriorated during the CSWS period in both patients. The autonomic seizures and focal to bilateral tonic‐clonic seizures were initially resistant to antiepileptic drugs (AEDs), and occurred more than 10 times in both patients. However, the seizures and EEG findings gradually resolved, and AEDs were successfully terminated in both patients. Conclusion: PS can progress to ESES if the clinical course exhibits atypical evolution. The initial autonomic symptom of the seizures and interictal Fp‐O EEG foci should be carefully monitored in patients with CSWS or ESES.     

Scalp‐recorded high‐frequency oscillations in childhood sleep‐induced electrical status epilepticus

Because high‐frequency oscillations (HFOs) may affect normal brain functions, we examined them using electroencephalography (EEG) in epilepsy with continuous spike‐waves during slow‐wave sleep (CSWS), a condition that can cause neuropsychological regression. In 10 children between 6 and 9 years of age with epilepsy with CSWS or related disorders, we investigated HFOs in scalp EEG spikes during slow‐wave sleep through temporal expansion of the EEG traces with a low‐cut frequency filter at 70 Hz as well as through time‐frequency power spectral analysis. HFOs (ripples) concurrent with spikes were detected in the temporally expanded traces, and the frequency of the high‐frequency peak with the greatest power in each patient’s spectra ranged from 97.7 to 140.6 Hz. This is the first report on the detection of HFOs from scalp EEG recordings in epileptic patients. We speculate that epileptic HFOs may interfere with higher brain functions in epilepsy with CSWS.     

Sulthiame add-on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES)

Purpose: In children with symptomatic or idiopathic focal epilepsies, their disease may evolve into an epileptic encephalopathy related to continuous spike and wave during slow sleep (CSWS) or electrical status epilepticus during slow sleep (ESES). ESES syndrome implies serious risks of neuropsychologic impairment, and its treatment has frequently been disappointing. The aim of this study is to present our experience using sulthiame as add‐on treatment in 53 patients with ESES syndrome that was refractory to other antiepileptic drugs (AEDs). Methods: Neurologic examinations, cerebral magnetic resonance imaging (MRI), and repeated prolonged sleep electroencephalography (EEG) studies were performed in all cases. Data about school achievements and or neuropsychological evaluations were obtained repeatedly during the follow‐up of 1.5–16 years. Sulthiame was added in doses ranging between 5 and 30 mg/kg/day. Key Findings: Since add‐on of sulthiame, 10 of 28 patients in the symptomatic group became seizure free: 4 patients with normal EEG studies and 6 with residual spikes. Nine of 28 patients showed a significant reduction in number of seizures and presented spikes but no ESES on EEG. The other nine cases showed neither clinical nor EEG improvement. A striking result was that 3 of 11 children with unilateral polymicrogyria and ESES syndrome became seizure free, and in another six a significant improvement in frequency of seizures and in EEG abnormalities seemed to be related to the add‐on of sulthiame. Twenty‐one of the 25 patients in the idiopathic group became seizure free and without ESES in <3 months after add on of sulthiame. In two of the patients the changes were seen in a few days. Significance: We understand that sulthiame may be effective as add‐on treatment in children with ESES syndrome.     

Detection of epileptic spikes by magnetoencephalography and electroencephalography after sleep deprivation

IntroductionIn diagnosis of epilepsies electrophysiological findings play a key role. While spontaneous electroencephalography (EEG) and EEG with sleep deprivation (EEGsd) are widely evaluated and used, application of magnetoencephalography (MEG) in this field is primarily limited to presurgical assessment of focal epilepsies.MethodsIn this study we retrospectively compared MEG (M/EEG) and EEGsd in 63 (55) patients with focal and generalized epilepsy with regard to occurrence of epileptic spikes.ResultsMEG could record epileptic spikes in 38 patients (60%), while EEGsd recorded spikes in only 32 patients (51%). In a group of 55 patients simultaneous MEG/EEG (M/EEG) was able to record spikes in 38 patients (71%) compared to epileptic spikes in 28 patients (51%) recorded by EEGsd. In a subgroup of 17 MR-negative patients simultaneous M/EEG could record epileptic spikes in all patients, while EEGsd was successful in only 11 (64%) of them.ConclusionIn this study, MEG showed a tendency to record epileptic spikes in more patients than EEGsd. Furthermore, simultaneous M/EEG has been shown to be especially successful in detection of epileptic spikes in patients with MR-negative epilepsy. This might at least in parts be explained by neocortical predominance of MR-negative epilepsy. Thus, this study motivates prospective studies to evaluate the substitutability of EEGsd by MEG more extensively.     

Magnetoencephalography localizing spike sources of atypical benign partial epilepsy

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 8.8 years (median, 2.9 years). 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.     

Idiopathic focal epilepsies: the “lost tribe”

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010 ), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many “treats” for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age‐related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow‐wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro‐temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau‐Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro‐clinical features warranting inclusion. In addition, a number of less well‐defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The term “benign” is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research. A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence‐free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice. Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the “unknown cause” classification and strongly suggest a genetic aetiology. The IFE are strongly age‐related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age‐related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state‐of‐the‐art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of “Luke's Idiopathic Focal Epilepsy Project” to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high‐frequency oscillations, and parental resources (see www.childhood-epilepsy.org ). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.     

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.     

Correlation between scalp high-frequency oscillations and prognosis in patients with benign epilepsy of childhood with centrotemporal spikes

Aims

The study aimed to explore whether high-frequency oscillations (HFOs) can predict seizure risk and atypical manifestations of benign epilepsy of childhood with centrotemporal spikes (BECTS).

Methods

We recruited 60 patients and divided them into three groups: (1) seizure-free BECTS, (2) active typical BECTS, and (3) active atypical forms of BECTS. Electroencephalogram was used to record the number, location, average amplitude, and duration of spikes, and spike ripples were analyzed using time-frequency technology. Multivariable logistic regression analysis was used to investigate independent predictive factors for prognosis.

Results

The number of sleep spike ripples, rather than spikes, was an independent risk factor for the active period of the disease (odds ratio [OR] = 4.714, p = 0.003) and atypical forms of BECTS (OR = 1.455, p = 0.049); the optimal thresholds for the spike ripple rate were >0 (area under the curve [AUC] = 0.885, sensitivity = 96.15%, specificity = 73.33%) and >0.6/min (AUC = 0.936, sensitivity = 84.21%, specificity = 96.15%), respectively. Furthermore, in typical BECTS, the spike ripple rate showed significant negative correlations with time since the last seizure (ρ = −0.409, p = 0.009) and age (ρ = −0.379, p = 0.016), while the spike rate did not.

Conclusion

Spike ripple was a marker for distinguishing typical and atypical forms of BECTS and reflected the risk of seizure recurrence better than the spike alone. The present findings might assist clinicians in BECTS treatment.     

Spatial and temporal dynamics of epileptic activity at sleep onset in the Encephalopathy with Status Epilepticus during slow sleep (ESES) after unilateral thalamic lesions

ObjectiveEncephalopathy with Status Epilepticus during slow Sleep (ESES) is a syndrome where neurocognitive impairment correlates with multifocal Electroencephalography (EEG) spikes increasing abruptly at sleep onset. Demonstration of a focal onset could provide important clues to unravel the mechanisms underlying the condition, but until know it has not been established.MethodsWe studied epileptic dynamics at sleep onset to assess its focal or diffuse features in five patients with perinatal thalamic hemorrhages lateralized to one hemisphere, using high resolution EEG.ResultsDynamical functional connectivity revealed the information flow in the epileptic network and identified primary sources of outflow, equated with cortical spike sources. We found that spikes with important activation originate in restricted cortical areas of the hemisphere with the lesion, spreading widely and quickly at onset of N2 sleep stage.ConclusionsPerinatal thalamic lesions have the potential to induce, years later, a regional onset of epileptic activity with features of ESES in a cortex without apparent structural lesion. Most widespread spike activity in the scalp results from secondary propagation.SignificancePerinatal thalamic lesions produce ESES with focal onset in a restricted cortical area of the hemisphere with the lesion, and prominent secondary propagation.     

Characteristics of dipoles in clustered individual spikes and averaged spikes

The aim of this study is to analyze the characteristics of dipoles in clustered individual spikes and averaged spikes, we compared electroencephalography (EEG) dipole localizations from patients with intractable extratemporal lobe epilepsy (IETLE) and from patients with benign epilepsy with centrotemporal spikes (BECTS).We studied 10 patients; five with IETLE who underwent epilepsy surgery after subdural EEG and five with BECTS. We recorded 19-channel digital scalp EEGs and used clustering analysis for individual spikes to characterize interictal spikes. We selected and averaged one representative spike group at the maximum negative peak electrode. We used a single dipole method with three-shell spherical head model. We compared dipole localizations of both averaged and individual spikes.IETLE data had more identifiable spike clusters and fewer spikes in each cluster than BECTS (P<0.05). Dipole sources with goodness-of-fit >or=95% in averaged spikes were less frequent in IETLE than in BECTS (P<0.05). For IETLE, averaged spikes showed no dipoles (two patients), while individual spikes gave dipole sources reliably in the epileptic region. For BECTS, individual and averaged spike sources were clustered. More than 80% of dipoles in averaged spikes were stable, in close proximity, for prolonged periods in BECTS.More spike groups after clustering and fewer acceptable dipoles from averaged spikes in IETLE reflect variable spike activity over extensive epileptic regions. Fewer spike groups producing more acceptable dipoles in BECTS correlate with stable spike sources within the isolated epileptic central region. Characteristics of clustered interictal spikes need careful examination before the use of dipole analysis of averaged spikes for epilepsy evaluation.     

Scalp-recorded high-frequency oscillations in childhood epileptic encephalopathy with continuous spike-and-wave during sleep with different etiologies

Objective

To investigate high-frequency oscillations (HFOs) in epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) with different etiologies.

Measuring spike strength in patients with continuous spikes and waves during sleep: Comparison of methods for prospective use as a clinical index

ObjectiveTo compare methods of estimating spike strength as a potential index in the assessment of continuous spikes and waves during sleep (CSWS).MethodsSpikes were searched and averaged automatically from pre- and postoperative EEGs of ten patients with CSWS who underwent corpus callosotomy (eight) or resective epilepsy surgery (two). From the most prominent spike, we measured peak amplitude and root mean square (RMS) over ±150 ms window around the peak. In order to compensate for spatiotemporal instability of spikes, the cumulative amplitude and RMS were computed from the highest quartile of electrodes (Ampl-Q and RMS-Q, respectively). The stability of parameters was studied by comparing two ten minute epochs during the first hour of NREM sleep, as well as by analyzing overnight variation of indices in further ten patients with CSWS. The Ampl-Q and RMS-Q were compared between pre- and postoperative recordings.ResultsAll four measures, amplitude, RMS, Ampl-Q and RMS-Q, were correlated with each other and highly dependent on NREM/REM-sleep stage and arousals. Expectedly, Ampl-Q and RMS-Q had the greatest intra-individual stability. The amplitude had up to 71% intra-individual variation making it unhelpful for clinical use. Ampl-Q and RMS-Q were comparable in assessing change following surgical treatment.ConclusionsComputing an integrated RMS over multiple electrodes during steady NREM sleep offers a stable and reliable parameter for evaluating the strength of spikes in CSWS.SignificanceAnalyzing spike strength with RMS-Q may offer a clinically useful, supplementary index for EEG monitoring of CSWS where spike index has been of limited value.     

Panayiotopoulos syndrome: diagnosis and management

Abstract Panayiotopoulos syndrome is a relatively frequent and benign epileptic syndrome, characterised by predominantly autonomic symptoms and/or simple motor focal seizures followed or not by impairment of consciousness. Interictal EEG shows occipital spikes although multifocal spikes with high amplitude sharp-slow wave complexes at various locations can be present. This syndrome can imitate gastroenteritis, encephalitis, syncope, migraine, sleep disorders or metabolic diseases. The peculiar aspects should be known not only by epileptologists but also by general doctors because a correct diagnosis would avoid aggressive interventions and concerns on account of its benign outcome. This review focuses on the main clinical and EEG features of this epilepsy underlining its typical and atypical symptoms and its management.     

Panayiotopoulos syndrome and diffuse paroxysms as the first EEG manifestation at clinical onset: a study of nine patients

Aim. To present a retrospective study of nine children with Panayiotopoulos syndrome associated with diffuse spikes and waves as the sole EEG manifestation at onset. Methods. Charts of children with typical clinical criteria of Panayiotopoulos syndrome, electroclinically followed between February 2000 and February 2012, were reviewed. Results. Among 150 patients who met the electroclinical criteria of Panayiotopoulos syndrome, we identified nine children who presented with the typical clinical manifestations but who, on EEG, only had diffuse paroxysms at onset that continued along the course of the syndrome. In three, in addition to the diffuse paroxysms, focal spikes appeared later. From a clinical point of view, other features were otherwise unremarkable. Diffuse spike‐and‐wave discharges were observed in all patients when awake and during sleep (100%). Later, three children also had focal spikes during sleep, which were occipital in one, frontal in one, and temporo‐occipital in the remaining patient. Spikes were activated by sleep in all three cases. During disease evolution, no particular electroclinical pattern was observed. Two patients who received clobazam and carbamazepine, respectively, did not respond well to the drugs and valproic acid was added with excellent seizure control. Outcome was good. Conclusions. We present evidence that patients with Panayiotopoulos syndrome may have diffuse discharges at onset as the sole EEG manifestation, which last throughout the course of the syndrome. In some, focal paroxysms developed later. The course was benign. In our group of patients, clinical features and evolution were similar to those of typical cases of Panayiotopoulos syndrome.     

Abstracts of the 38th Congress of the Japan Epilepsy Society, Shizuoka, Japan, September 30-October 1, 2004

Diagnosis and Treatment of Idiopathic Focal Epilepsies (Benign Partial Epilepsies) in Infancy and Childhood. ¹ Tamiko Negoro ( ¹ Department of Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan ). Introduction: According to the revised classification of epilepsies and epileptic syndromes proposed by the Commission on Classification and Terminology of the International League Against Epilepsy (1989), benign childhood epilepsy with centrotemporal spikes (BCECT), childhood epilepsy with occipital paroxysms (Gastaut‐type late‐onset CEOP), and primary reading epilepsy were included in the idiopathic localization‐related epilepsies (ILRE). Since then, new epileptic syndromes such as Panayiotopoulos‐type early‐onset benign childhood occipital epilepsy (also known as benign childhood epilepsy with occipital paroxysms or BCEOP) and benign partial epilepsies in infancy (BPEI) have been additionally included as ILRE. The diagnostic criteria for benign partial epilepsies include (1) normal neurological examination; (2) normal intelligence; (3) normal neuroimaging; (4) a family history of benign‐type seizures; (5) brief stereotyped seizures; (6) frequent nocturnal occurrence; (7) easy control with antiepileptic drugs (AEDs), except ethosuximide; and (8) remission before adolescence. The EEG features include (1) normal background activity; (2) spikes with a characteristic morphology and location; (3) sleep activation; and (4) occasional generalized paroxysms. In our 114 cases of childhood onset localization‐related epilepsies (LRE) diagnosed between 1997 and 2000, 48 cases (42%) were diagnosed as ILRE and 66 were cryptogenic or symptomatic LRE. Among the 48 ILRE cases, 28 (58%) were classified as BCECT, six (13%) as BPEI, five (10%) as BCEOP, two (4%) as atypical benign partial epilepsy, and seven (15%) as unclassified. Carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) were equally effective in controlling the seizures in our ILRE patients. This review describes briefly the diagnosis and treatment of BCECT, BCEOP, and BPEI. Benign Childhood Epilepsy with Centrotemporal Spikes: BCECT is the most common ILRE (also known as idiopathic focal epilepsies) in infancy and childhood. Sylvian seizures (simple partial seizures or focal motor or sensory seizures beginning unilaterally at the lower part of the face) and EEG findings (central‐midtemporal high‐amplitude, repetitive sharp waves) are quite stereotyped, and diagnosis of typical cases is relatively easy. Frontal lobe seizures with bilateral perioral twitches or unilateral eyelid twitches may sometimes be misdiagnosed as Sylvian seizures. Since status epilepticus is very rare and many patients only have occasional seizures, many physicians choose not to treat the disorder. If treatment is necessary, the seizures are usually easily controlled with carbamazepine, valproic acid, or clonazepam. Continuation of AEDs is not necessary after the EEG has normalized around puberty. The prognosis is excellent. However, a small percentage of patients may show atypical evolutions such as atypical benign partial epilepsy, epilepsy with continuous spike‐and‐waves in slow wave sleep, or epilepsy with centrotemporal spikes and oromotor deficit. Seizure and EEG exacerbations by AEDs, especially carbamazepine, have to be considered. Early recognition and proper treatment are necessary for these conditions. Benign Childhood Epilepsy with Occipital Paroxysms: BCEOP is also known as Panayiotopoulos‐type early‐onset benign childhood occipital epilepsy. The mean age at first seizure is around 5 years. Seizures comprise an unusual constellation of autonomic, mainly emetic, syndromes with unilateral deviation of the eyes and impairment of consciousness. Visual symptoms, which are the main symptoms in Gastaut‐type, late‐onset CEOP, are exceptions in BCEOP. According to our 41 cases examined between 1984 and 1993, two‐thirds of the patients show hemi‐ or generalized convulsions and one‐fourth experience prolonged seizures for longer than 30 minutes. EEG findings (bilateral occipital paroxysms) consist of some extraoccipital abnormalities especially in the frontal area (48% of our cases) or generalized paroxysmal discharges (32% of ours cases), together with various migrations of spike foci. EEG findings seem to normalize around the age of 10 years. Many patients only have occasional seizures and these seizures are usually easy to control with carbamazepine or valproic acid. The prognosis is excellent. Prevention of status epilepticus is the major problem in this disorder. Recently, new concepts including early‐onset benign occipital seizure susceptibility syndrome (EBOSS) and Panayiotopoulos syndrome (idiopathic susceptibility to early‐onset benign childhood seizures with mainly autonomic symptoms), have been introduced for BCEOP. Benign Partial Epilepsies in Infancy: BPEI comprise two forms. One is partial epilepsy with complex partial seizures (CPS) and the other is partial epilepsy with secondarily generalized seizures (SGS). Onset is mostly during the first year of life. Seizures often occur in clusters and are characterized by motion arrest, decreased responsiveness, staring or blank eyes often with automatisms, and mild convulsive movements in the CPS form; and motion arrest or opening of eyes with staring or blank eyes followed by generalized tonic–clonic seizures in the SGS form. Interictal EEGs mostly show no abnormal findings. According to the ictal EEGs, the most frequent site of seizure origin is in the frontal or temporal area in the CPS form; and central, parietal, or occipital area in the SGS form. Treatment with carbamazepine, phenobarbital, zonisamide or valproic acid immediately stops the cluster of seizures. The prognosis is excellent. Recently, sleep‐related and low‐voltage Rolandic and vertex spikes have been reported as an EEG marker of benignity in this disorder. Most of benign infantile convulsions may belong to partial epilepsy with SGS, although confirmation with ictal EEG recording is necessary for accurate diagnosis.     

Comparison of epileptic and nonepileptic cases with centrotemporal spikes in view of clinical findings and electroencephalographic characteristics

The morphological features of centrotemporal spike discharges (CTSD) and relationship of them with clinical diagnosis in cases with benign epilepsy of childhood with centrotemporal spikes (BECTS) and the other epileptic syndromes of childhood as well as some nonconvulsive neurological disorders were detected in the routine patient population who referred to the authors' EEG laboratory. Thirty-six cases (21 males, 15 females; 8 months-14 years old), in which awake and/or sleep EEGs revealed CTSD were included in this study. The cases were divided into two groups as epileptic and nonepileptic. The cases with seizure were divided into BECTS and the other epilepsies. Of the epileptic cases, 14 (38.8%) patients had typical rolandic seizures. In five cases, there were partial or secondary generalized seizures. Two cases had myoclonic seizures. In the nonepileptic group, there was mental retardation/behavioral disturbances in five cases; there were periodic syndromes of childhood such as migraine and equivalents of migraine in three cases; febrile convulsion in three cases, breath-holding spells in two cases, and primary enuresis nocturna in two cases. In the nonepileptic group, the discharges were significantly fewer than the other groups (p = .014). More frequent discharges occuring for shorter periods were more significantly observed in BECTS group (64%). Typically isolated spike and slow-waves in T3/T4 and C3/C4 location were significantly more common (86%) in rolandic epilepsy group (p = .01). The EEGs of cases with BECTS had more frequency in the cluster of discharges than the other groups (p = .018). Multifocal discharges were observed in 28.5% of cases with BECTS, in 20% of nonepileptic group, and in 71.4% of other epileptics in the trial. Although these epileptic and nonepileptic conditions have some differences in view of frequency and morphology and location, CTSDs could be manifested in the group without seizure. It was concluded that the similar focal abnormalities which could be seen in rolandic epilepsy may be observed in the other epileptic or nonepileptic disorders of childhood and this condition may be originated from the involvement of similar central structures.     

A skew-based method for identifying intracranial EEG channels with epileptic activity without detecting spikes,ripples, or fast ripples

ObjectiveTo develop a method for identifying intracranial EEG (iEEG) channels with epileptic activity without the need to detect spikes, ripples, or fast ripples.MethodsWe compared the skew of the distribution of power values from five minutes non-rapid eye movement stage N3 sleep for the 5–80 Hz, 80–250 Hz (ripple), and 250–500 Hz (fast ripple) bands of epileptic (located in seizure-onset or irritative zone) and non-epileptic iEEG channels recorded in patients with drug-resistant focal epilepsy. We optimized settings in 120 bipolar channels from 10 patients, compared the results to 120 channels from another 10 patients, and applied the method to channels of 12 individual patients.ResultsThe distribution of power values was more skewed in epileptic than in non-epileptic channels in all three frequency bands. The differences in skew were correlated with the presence of spikes, ripples, and fast ripples. When classifying epileptic and non-epileptic channels, the mean accuracy over 12 patients was 0.82 (sensitivity: 0.76, specificity: 0.91).ConclusionsThe ‘skew method’ can distinguish epileptic from non-epileptic channels with good accuracy and, in particular, high specificity.SignificanceThis is an easy-to-apply method that circumvents the need to visually mark or automatically detect interictal epileptic events.     

Sleep and epilepsy

This review considers the effect of sleep on seizures and interictal electroencephalogram (EEG) paroxysmal activities (PAs), as classified by the International League Against Epilepsy criteria. No type of seizure is, per se, specifically linked with non-rapid eye movement (NREM) or rapid eye movement (REM) sleep. However, in some syndromes, seizures are more frequent in slow wave sleep (SWS) [partial motor or generalized seizure in benign epilepsy with centro-temporal spikes (BECTS), frontal seizures in idiopathic familial or not familial frontal lobe epilepsy and generalized tonic seizure in secondary generalized epilepsy are increased by SWS]. Conversely myoclonia and grand mal seizures are associated with awakening in some forms of generalized idiopathic epilepsy. There is a mean increase in PAs during SWS in generalized and in partial epilepsies on the whole. However, precise analysis shows that in partial cryptogenic or symptomatic epilepsy and, most likely, in the majority of generalized idiopathic epileptic syndromes about 20% of patients have an increase in PA density during SWS, 20% experience an increase in waking, 50% have very few PAs and in 10% there is no significant difference between sleep and waking. BECTS, however, exhibits a definite increase in sleep PA increase and in juvenile myoclonic epilepsy an increase in PAs during the intra-night awakening is reported. There are at least three syndromes, which cause a huge increase in PAs during sleep: the Landau-Kleffner syndrome and the syndromes of continuous focal or generalized spike-waves during SWS. Their physiopathology and neuropsychological consequences are discussed. Neurophysiological animal data are also reported highlighting the relationships between slow sleep oscillations and the generation of spike waves. A biochemical review is also presented.