The localization-related epilepsies: some problems with subclassification

One of the nosological problems of childhood epilepsies is the evolutionary change of foci with age. Benign childhood epilepsy with centro-temporal spike may evolve to show EEG features of childhood epilepsy with occipital paroxysms and vice versa. West syndrome is generally accepted as generalized epilepsy but is often preceded or followed by partial seizures and may have both partial seizures and tonic spasms in a single attack. Among epilepsies with both generalized and focal seizures, severe myoclonic epilepsy in infancy is more linked to generalized epilepsy whereas epilepsy with continuous spike-waves during slow wave sleep is more linked to localization-related epilepsy. Any type of partial epilepsy may develop nonconvulsive generalized seizures transiently with generalization of paroxysmal discharges during the clinical course. Moreover, nonconvulsive generalized seizures may occur even in localization-related epilepsy with spike-wave index during NREM sleep in less than 85%.     

The Localization-Related Epilepsies: Some Problems with Subclassification

Abstract: One of the nosological problems of childhood epilepsies is the evolutionary change of foci with age. Benign childhood epilepsy with centro-temporal spike may evolve to show EEG features of childhood epilepsy with occipital paroxysms and vice versa. West syndrome is generally accepted as generalized epilepsy but is often preceded or followed by partial seizures and may have both partial seizures and tonic spasms in a single attack. Among epilepsies with both generalized and focal seizures, severe myoclonic epilepsy in infancy is more linked to generalized epilepsy whereas epilepsy with continuous spike-waves during slow wave sleep is more linked to localization-related epilepsy. Any type of partial epilepsy may develop nonconvulsive generalized seizures transiently with generalization of paroxysmal discharges during the clinical course. Moreover, nonconvulsive generalized seizures may occur even in localization-related epilepsy with spike-wave index during NREM sleep in less than 85%.     

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.     

Sleep and the epilepsies

To review the numerous works concerning sleep and epilepsy, this review considers the effects of sleep, firstly on seizures and secondly on paroxysmal interictal EEG activity (PA), in the different types of epilepsy according to the International League against Epilepsy classification. Apart from the exceptions of the definite nocturnal preponderance of seizures in idiopathic rolandic epilepsy and of the mostly nocturnal occurrence of seizures in some types of familial or sporadic frontallobe epilepsy, assessing a seizure according to the time of day it occurs is of no diagnostic or predictive value. In generalised idiopathic epilepsy, as in partial symptomatic or cryptogenic epilepsy, only about 20% of the patients had a sleep increase in PA. This percentage is higher (75%) in idiopathic partial epilepsy. Stereoelectroencephalography demonstrates a relative stability of spiking within the fouus across the states of vigilance and an increase in transmitted discharges during stages 3 and 4. In the Landau and Kleffner syndrome, as in the syndromes of continuous spike-waves during sleep, there is a huge, unexplained increase in PA during sleep. The neuropsychological consequences of this PA have some relationship with their localisation and the patient’s age at the time of occurrence. Sleep PA has also been reported in several groups of non-epileptic subjects. As regards the effect of epilepsy on sleep, sleep may be lighter and abnormally discontinuous in the absence of seizures, particularly in temporallobe epilepsy.

     

Paroxysmal activity and seizures associated with sleep breathing disorder in children: A possible overlap between diurnal and nocturnal symptoms

PurposeSleep breathing disorders (SBD) can trigger paroxysmal events. We recently found a higher percentage of paroxysmal activity (PA) in a sample of Italian children with obstructive sleep apnea syndrome (OSAS) and no history of epilepsy. The signs of nocturnal seizures can overlap with sleep respiratory events. The aim of this study was to confirm the high frequency of PA or interictal epileptiform discharges (IEDs) during sleep in a cohort of Spanish children who underwent polysomonography (PSG) for suspected SBD and to ascertain the eventual presence of seizures by means of a video-PSG with an extended electroencephalogram (EEG).MethodsPSG was performed in a population of children with no previous history of epileptic seizures recruited prospectively for suspected OSAS from January to December 2007. Recordings included at least 13 EEG channels.ResultsIn total, 25 children (mean age, 6.6 ± 3.8 years, 14 males) were diagnosed with SBD, and 4/25 (16%) children met the criteria for OSAS and epilepsy, with IEDs and/or seizures during sleep. We diagnosed benign epilepsy with centro-temporal spikes in 2 cases, partial symptomatic epilepsy in one, and nocturnal frontal lobe epilepsy in another, while we found PA in 2 patients. The body mass index and the apnea–hypopnea index were significantly higher in children without IEDs/PA.ConclusionsOur study demonstrated a close relationship between pediatric SBD, PA during sleep, and epilepsy that may aggravate the prognosis of SBD. Due to the possibility of an overlap of symptoms, a video-PSG with extended EEG montage is necessary.     

一组特殊的良性儿童部分性癫(癎)的临床和脑电图特征

目的 分析一组特殊的良性儿童部分性癫(癎)的临床特征,探讨其病理生理机制.方法 对在我院癫(癎)中心门诊就诊的儿童部分性癫(癎)进行随访观察,纳入符合良性部分性癫(癎)诊断者,排除能够分类的其他类型,分析患者的临床和脑电图特征.结果 入组的44例患者中,38.6%(17/44)的患儿每天均有发作,额叶失神、偏转是最常见的发作症状,觉醒脑电图有局灶、多灶、全面性棘慢波爆发3种表现,且以额部为著;睡眠时双侧同步化.截止随访日,88.6%(39/44)完全无发作,22.7%(10/44)脑电图完全恢复正常.结论 有一组特殊的良性儿童部分性癫(癎),可能是起源于额叶.     

Paroxysmal visual disturbances of epileptic origin and occipital epilepsy in children

A special form of partial occipital epilepsy clinically resembling migraine and possibly related to the benign focal epilepsies of childhood has recently attracted attention (Gastaut 1982) but its existence is still debated. To approach this problem, in a group of 195 children with idiopathic partial or generalized epilepsy we have studied those who had visual complaints as part of their seizures (twelve children) and those who also had migraine (four children). The clinical and electroencephalographic features of these children were analyzed together with those of another group of thirty children diagnosed as migraine accompagnée in which an EEG had been obtained (3/30, i.e. 10% had paroxysmal spike-waves: one centrotemporal focus, two generalized spike-waves). One child with the type of epilepsy described by Gastaut (1982) as partial benign occipital epilepsy (phosphenes, moving lights, headaches and occipital high voltage biphasic spike-waves blocked by eye opening on the EEG) was found in the epileptic group whereas the other children of this group, including those with associated migraine, had other types of epilepsy. This "new" type of epileptic syndrome can be distinguished from symptomatically resembling entities but its place needs to be further defined.     

Reflex occipital lobe epilepsy.

Photosensitivity is a typical feature of photosensitive epilepsy which is usually considered a form of idiopathic generalized epilepsy. Partial seizures featuring visual symptoms are rarely reported in photosensitive epilepsy. In this study, we describe 13 neurologically normal patients in whom daytime seizures were always induced by television and began with elementary visual hallucinations, followed frequently by vomiting, headache and then secondary generalization. Three patients additionally reported nocturnal seizures, which have not been described in previous studies. Two of these latter patients had generalized tonic-clonic seizures, the other always awoke from sleep and could describe typical visual hallucinations at the beginning of the seizure. EEG features included normal background activity and occipital spikes or spike-waves in all but two patients. Eight patients also showed generalized epileptiform activity during intermittent photic stimulation. Seizure frequency was low in all. Apart from two patients, who refused treatment, all patients received antiepileptic drugs. Only one patient continued to have rare seizures after treatment; in the others seizure control was achieved with monotherapy. We conclude that reflex occipital lobe epilepsy is an idiopathic form of the benign partial epilepsies, which may overlap with one another.     

Benign partial epilepsy of childhood: a longitudinal neuropsychological and EEG study of cognitive function

The study combined prospective neuropsychological and EEG results of 22 children presenting with typical benign partial epilepsy with rolandic spikes (n=19) and occipital spikes (n=3). The aims were to assess the types of cognitive problems which may be encountered in this population, to evaluate the course of cognitive and learning capacities during the active phase of epilepsy, and to see if there was a correlation with paroxysmal activity on the EEG. Average age at entry in the study was 8.4 years and each child was seen two to four times over a period of 1 to 3 years. EEGs showed persistent spike foci in most cases that worsened in three cases, but there were no continuous spike-waves during sleep. No child had persistent stagnation, marked fluctuations, or a regression in cognitive abilities. Of 22 children, 21 had average IQ (>80). Eight children had school difficulties requiring special adjustment. No single cognitive profile was identified. Four children had delayed language development and eight children had transient weak scores in one isolated domain (verbal, visuospatial, memory) which improved or normalized during the course of the study with concomitant EEG improvement or normalization. In two of the three children with aggravation of the paroxysmal EEG activity, clinical changes were documented. A proportion of children with typical benign partial epilepsy with rolandic spikes showed mild, varied, and transient cognitive difficulties during the course of their epilepsy, and in most cases this probably had a direct relation with the paroxysmal EEG activity.     

Event-related potential (P300) in two epileptic cases with continuous spike-waves during slow wave sleep

We studied the P300 of two epileptic cases with almost continuous diffuse spike-wave discharges on sleep EEG: one with epilepsy with continuous spike-waves during slow wave sleep, and another with atypical benign partial epilepsy. These cases showed a marked prolongation of P300 latencies during nonconvulsive status epilepticus with continuous spike-waves during slow wave sleep. As they improved clinically and electroencephalographically, the latencies became normal. These findings indicate that P300 is a useful method to elucidate the pathophysiology of nonconvulsive status epilepticus with continuous spike-waves during slow wave sleep.     

Paroxysmal nocturnal activity in partial epilepsy in the adult

Thirty-four adults with partial epilepsy underwent polysomnographic sessions. Three sub-groups of patients were determined by timing their EEG paroxysmal activities (PA) according to the possible increase in PA related to their sleeping or awake state. Twenty-seven had an increase in PA when sleeping, 5 when awake and no significant difference was found in two other patients. Patients who suffered from nocturnal or partial elementary epileptic seizures were those who showed a PA increase when in a sleep state. These patients had a lower PA density during a waking state than the patients with a PA increase when awake. The more synchronized (stages 3 + 4) and desynchronized (waking) cortical states influence the PA densities in such a way that there is a significant difference between both sub-groups. The PA density modulation found with the slow-wave sleep stages adds to that induced by sleep and waking states.     

Partial epilepsy in neurologically normal children: clinical syndromes and prognosis

A clinical and electroencephalographic study of 107 neurologically normal children with partial seizures was undertaken to verify the existence and determine the frequency of epileptic syndromes reported in selected populations. Sixty-three children had simple partial seizures, 39 had complex partial seizures, and 5 children were unclassifiable. The syndrome of benign partial epilepsy of children with rolandic spikes (BPEC, 38 cases) was clearly identified and its uniformly benign final prognosis was confirmed even if some of these children had at times severe or poorly controlled seizures. Among the children with simple partial seizures outside the BPEC (25 cases) and complex partial seizures (39 cases), no homogeneous clinical or electroclinical subgroup could be found. Two children with benign partial epilepsy and myoclonic-astatic seizures ("atypical benign partial epilepsy of childhood") and one child with "benign epilepsy with occipital spike-waves" were identified. 74% of children with epilepsy with complex partial seizures (ECP) had a 1-year seizure-free interval, and many children with epilepsy with simple partial seizures outside the BPEC group (ESP) had no more than two seizures. A benign course is thus not limited to the BPEC but is difficult to predict. Prospective studies are necessary to confirm the existence of well-defined benign syndromes among the idiopathic partial epilepsies of childhood, which appear quite rare outside the BPEC.     

The spectrum of benign infantile seizures

Benign epilepsies during infancy are a wide topic, which needs both clinical and nosological clarifications. Already in 1963 Fukuyama reported patients with seizures during infancy with a benign outcome. In the late 80s and early 90s, Watanabe reported series of infants with complex partial seizures or partial seizures with secondary generalization, with a normal development before onset and a benign outcome. In the same years Vigevano focused on familial cases: he described several families with seizures with onset around the 6-month of age, and autosomal dominant mode of inheritance. To define this condition, he coined the term "benign familial infantile seizures" (BFIS). Afterwards, studying families with this phenotype, loci on chromosomes 19, 16 and 2 responsible for BFIS were detected. Similar loci were found in families affected by BFIS and subsequent choreoathetosis, and BFIS associated with familial hemiplegic migraine. In most recent years a new form of benign epilepsy has been proposed, with an intermediate onset between the neonatal and infantile age, which was defined with the term benign familial neonatal-infantile seizures (BFNIS). This condition could have some clinical and genetic features overlapping with BFIS. Seizures with a benign outcome have been reported also in infants during episode of mild gastroenteritis (BIS with MG) frequently with positive Rotavirus antigen. Lastly, sleep EEG abnormalities have been reported in children with a peculiar form of epilepsy by Capovilla, who defined this condition as benign infantile focal epilepsy with midline spikes and waves during sleep (BIMSE). Some of these entities have been included in the last classification proposed by the ILAE and have been differentiated in familial and non-familial forms. The aim of this review is to describe these entities, discuss their nosological aspects, pointing out the similarities and differences with benign neonatal seizures and benign focal epilepsies appearing later in life such as early-onset benign occipital seizure susceptibility syndrome (EBOSS), or benign epilepsy of childhood with centro-temporal spikes (BECTS).     

Autosomal dominant rolandic epilepsy and speech dyspraxia: A new syndrome with anticipation

We describe a family of 9 affected individuals in three generations with nocturnal oro-facio-brachial partial seizures, secondarily generalized partial seizures, and centro-temporal epileptiform discharges, associated with oral and speech dyspraxia and cognitive impairment. The speech disorder was prominent, but differed from that of Landau-Kleffner syndrome and of epilepsy with continuous spike and wave during slow-wave sleep. The electroclinical features of this new syndrome of autosomal dominant rolandic epilepsy resemble those of benign rolandic epilepsy, a common inherited epilepsy of childhood. This family shows clinical anticipation of the seizure disorder, the oral and speech dyspraxia, and cognitive dysfunction, suggesting that the genetic mechanism could be expansion of an unstable triplet repeat. Molecular studies on this syndrome, where the inheritance pattern is clear, could also be relevant to identifying a gene for benign rolandic epilepsy where anticipation does not occur and the mode of inheritance is uncertain.     

Panayiotopoulos syndrome: a prospective study of 192 patients

OBJECTIVES: To characterize the electroclinical features and evolution of Panayiotopoulos Syndrome (PS). METHODS: Children with electroclinical criteria of PS were prospectively identified and followed-up clinically, and with sleep and awake EEGs between February 1990 and 2006. RESULTS: We identified 192 patients with PS. In the same length of time 398 children with benign childhood epilepsy with centro-temporal spikes (BCECTS) were registered. PS had a peak age at onset of 5 years. Autonomic manifestations were one of the most common ictal event. Ictal deviation of the eyes and progression to generalized convulsions were also quite frequent. Approximately one third had partial status epilepticus. In all patients except five, the seizures occurred during sleep. One-third also had fits while awake. Sixteen children had concomitant symptoms of rolandic epilepsy and eight developed rolandic seizures after remission of PS seizures. Prognosis was excellent. Eighty-four (44.2%) had a single seizure, 79 (41.2%) had 2-5 fits, and 28 (14.6%) had frequent seizures. CONCLUSION: PS is less common than BCECTS, but is well defined and easily recognizable by clinical and EEG features, with autonomic manifestations as one of the most common ictal event.     

Benign familial infantile seizures: further delineation of the syndrome

Benign familial infantile seizures are an autosomal dominant epilepsy disorder that is characterized by convulsions, with onset at age 3 to 12 months and a favorable outcome. Benign familial infantile seizures have been linked to chromosome 19q whereas infantile convulsions and choreoathetosis syndrome, in which benign familial infantile seizure is associated with paroxysmal choreoathetosis, has been linked to chromosome 16p 12-q12. Many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 infantile convulsions and choreoathetosis syndrome region. Moreover, in one large pedigree with paroxysmal kinesiogenic dyskinesias only, the syndrome has also been linked to the same genomic area. Families with pure benign familial infantile seizures may be linked to chromosome 16 as well. In this study, we present a series of 19 families and 24 otherwise healthy infants with benign familial infantile seizures. Two of these families include members affected with benign familial infantile seizures and paroxysmal choreoathetosis. We included patients with normal neurologic examinations, who started having simple partial seizures, complex partial seizures, or apparently generalized seizures without recognized etiology between 2 months and 2 years of age. Neurologic studies were normal, but in all patients, there was a history of similar seizures and age at onset in either the father or the mother. Twenty-four patients (14 girls and 10 boys) were evaluated at our hospital between February 1990 and February 2001. Age at onset, sex, family history of epilepsy and/or paroxysmal dyskinesias, neurologic examination, semiology, distribution, and frequency and duration of seizures were evaluated. Electroencephalographic (EEG) and neuroradiologic studies were also performed. Seizures began between 3 and 22 months of life, with a median age of 5 1/2 months. Nine patients (37.5%) had only apparently generalized seizures, 5 patients (20.8%) had only partial seizures, and 10 patients had both partial and apparently generalized seizures (41.6%). Seizures were invariably brief, occurred during the waking state (100%), and presented mainly in clusters in 12 patients (50%). Interictal EEG was normal in 23 patients (95.8%). Sixteen patients (66.6%) had a confirmed history of convulsions in family members other than parents. Twenty-two patients became seizure free after 30 months of life. Two brothers in the same family had brief paroxysmal episodes of choreoathetosis in the hemibody triggered by stress while awake at 15 and 17 years old, respectively. One of them had paroxysmal choreoathetosis only, and the other was associated with benign familial infantile seizures. One father had brief spontaneous episodes of paroxysmal choreoathetosis when awake at age 18 years. All of them had a good response to antiepilepsy drugs, and neurologic examination and EEG and neuroradiologic studies were normal. Benign familial infantile seizure is a genetic epilepsy syndrome with autosomal dominant inheritance. It may be associated with paroxysmal choreoathetosis (infantile convulsions and choreoathetosis syndrome), which has been linked to the chromosome 16 infantile convulsions and choreoathetosis syndrome region. Patients in families with infantile convulsions and choreoathetosis syndrome could display either benign familial infantile seizures or paroxysmal choreoathetosis or both. It is likely that the disease in families with pure benign familial infantile seizures may be linked to the infantile convulsions and choreoathetosis region as well. We cannot exclude the possibility that the youngest patients may develop choreoathetosis or other dyskinesias later in life.     

Differential aspects of sleep epilepsy

A review of patients with epilepsy showed that 5.9% had seizures exclusively in sleep (ES) and 4.7% had seizures predominantly but not exclusively in sleep (PS). These groups were compared with a group (W) with seizures mainly in wakefulness. The following significant differences were obtained: 1) generalized convulsions predominated in the ES while partial seizures were more common among PS and W patients, 2) seizures occurred less frequently in the ES group, and 3) more W patients had EEGs with generalized epileptiform activity and positive family histories for epilepsy. We suggest the lower frequency of seizures in the ES group and the declining prevalence of sleep epilepsy are due to: 1) the high proportion of generalized as opposed to partial seizures in sleep and 2) more effective control of generalized seizures compared to partial seizures by modern anti-epileptic drug management.     

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.