Epilepsy & Seizures

Updated 03.23.2022
Released 10.18.1993
Expires For CME 03.23.2025

Self-limited epilepsy with centrotemporal spikes

Authors: K P Vinayan MD DM, Arushi Gahlot Saini MD DM MNAMS

Editor: Solomon L Moshé MD

Introduction

Overview

Self-limited epilepsy with centrotemporal spikes (SLECTS) is the new name for the previous epilepsy syndrome of benign epilepsy with centrotemporal spikes (BECTS). It was first reported in the 1950s and is now recognized as the most frequent epilepsy syndrome in children between the ages of 4 and 13 years. The term “benign” was applied to this syndrome to differentiate it from other sinister causes for focal epilepsies. However, it was subsequently noted that dysfunctions in cognitive and language domains as well as atypical evolutions with a not-so-benign course are seen in this syndrome. As per the current epilepsy classification, the new term “self-limited” has replaced the term “benign.” The common idiopathic focal epilepsies of childhood are increasingly being termed “self-limited focal epilepsies of childhood” (SFEC) and at times, the word “benign” is completely omitted to name the syndrome as “childhood epilepsy with centrotemporal spikes” (CECTS). For the purposes of this review, we are using the term self-limited epilepsy with centrotemporal spikes (SLECTS) for the typical cases to maintain uniformity. Atypical evolutions after a seemingly classical onset as well as clinical variants are discussed separately. Emerging data on cognitive impairment in children with SLECTS have also been described.

Key points

	• The defining feature of SLECTS is the presence of classical centrotemporal spikes on interictal EEG. However, these are not specific to this syndrome. Centrotemporal spikes may be seen in children without seizures, with other epilepsy syndromes, and with structural lesions in the rolandic area. Moreover, the typical seizures in SLECTS may be seen without the classical spikes on the interictal record.
	• An increasing frequency of specific cognitive, language, memory, and attention-related disorders are being reported in children with SLECTS.
	• Atypical clinical and EEG features are usually seen with transitory cognitive and language impairments.
	• Very rarely, SLECTS may evolve into Landau-Kleffner syndrome and continuous spike-and-waves during slow sleep syndrome with potential for persistent neuropsychological impairments.

Historical note and terminology

Rolandic (centrotemporal) region is named after Luigi Rolando (1773-1831), an Italian anatomist known for his pioneer research in localization of function in the human brain. A particular EEG pattern with migratory spikes originating over the rolandic region was first reported in the 1950s (63; 68). In 1958, the first clinical description associated with EEG features was published (125). The same EEG pattern was later correlated with a common form of focal childhood epilepsy, then called "midtemporal epilepsy," characterized by hemifacial and oropharyngeal ictal symptoms and a favorable prognosis (67). Because of the localization of the ictal events, Lombroso proposed the term "sylvian seizures" (114). In the same year, Loiseau and colleagues presented an electroclinical series of 122 children with what they called “a particular form of epilepsy in childhood,” stressing its benign character. Several long-term follow-up studies at that time confirmed the good prognosis (10; 98; 113). This form of epilepsy was called “benign childhood epilepsy with centrotemporal spikes” and was placed in the group of idiopathic localization-related (focal, local, partial) epilepsies in the International Classification of Epilepsies and Epileptic Syndromes (28; 47). As new syndromes were recognized within the spectrum of benign childhood focal epilepsies (136), the term “benign” was considered initially acceptable for this syndrome but was considered inappropriate for some of the other idiopathic focal epilepsies (71).

However, the new ILAE Classification of the Epilepsies proposed the term “self-limited” for the “benign” course of epilepsies to reflect a “likely spontaneous resolution of a syndrome” (151). Hence, a new term “self-limited epilepsy with centrotemporal spike” (SLECTS) has been proposed for BCECTS (151). The common idiopathic focal epilepsies of childhood are increasingly being termed “self-limited focal epilepsies of childhood” (SFEC) and at times, the word “benign” is completely omitted to name the syndrome as “childhood epilepsy with centrotemporal spikes” (CECTS) (167).

Clinical manifestations

Presentation and course

Clinical features

Age. SLECTS begins between 2 and 13 years of age. In 80% of patients, seizures appear between 5 and 10 years of age. Patients usually recover before 16 years of age (10). The age at seizure onset has been proposed as the most important predictor of early remission, irrespective of the initial EEG findings, antiseizure medication treatment, or seizure frequency (96).

Ictal phenomenon. Most of the seizures reflect discharges in the precentral and postcentral gyri in the suprasylvian region with motor, sensory, and autonomic manifestations in the face, mouth, and throat (Loiseau and 10). This is associated independently with bilateral, repetitive, broad, centrotemporal interictal EEG spikes displaying a characteristic tangential bipolar pattern (70). The ictal manifestations are not indicative of temporal lobe involvement and the term “centro-temporal” refers only to the spike topography.

Seizures. Seizures are typically brief, lasting for 1 to 3 minutes. More than half of the patients retain consciousness and may recollect the sensations. Although focal seizures are characteristic of this disorder, generalized seizures may also be observed infrequently, particularly in younger children. The initial event is often a nocturnal hemifacial convulsion, which may spread to the arm and the leg, or may become secondarily generalized. The ictal patterns may vary from child to child and from seizure to seizure. Each individual patient usually has a single type of seizure, but 20% to 25% of children experience more than one type.

Oropharyngeal and facial manifestations. are the classical and initial manifestations of the seizures in most children. These include drooling from hypersalivation, swallowing disturbance, guttural sounds, involuntary movements or tonic contractions of the tongue or jaw, unilateral numbness or paresthesia of the tongue, lips, gums, and cheek, speech arrest (a form of anarthria), and myoclonic contraction of one side of the face.

Sensorimotor phenomena. may involve a leg or one half of the body. Miscellaneous symptoms such as abdominal pain may also occur rarely (Loiseau and 10). Among 230 children with SLECTS, six presented with sensory motor seizures in the leg as the main ictal manifestation (59).

Relation to sleep. More than one half of patients with SLECTS have seizures only during sleep, whether during the day or the night. Seizures during waking hours are more likely to occur shortly after awakening. Seizure frequency is usually low and around 10% of cases present only one seizure. However, in about 20% of children, seizures are frequent and may even occur several times per day (34). Onset before 3 years of age has been stated as the single most important predictor for multiple seizures (93; 192). Neither clinical features, seizure characteristics, nor routine EEG findings were found to be useful in predicting the likelihood of a second seizure in SLECTS (182). However, in a longer follow-up study of 52 children, the presence of a frontal focus and bilateral asynchrony were found to be correlated with the recurrence of seizures (163).

Behavioral problems. Behavioral disorders may be present in approximately one third of patients with SLECTS, including ADHD and oppositional defiant disorder (132). Early onset of seizures and the presence of bilateral interictal epileptiform discharges may suggest an increased risk for behavioral disorders in these children.

Sleep disturbances. Parents of children with SLECTS report a significantly shorter sleep duration, more frequent parasomnias, and increased daytime sleepiness (164).

Cognitive problems. Cognitive problems and low academic achievement might be seen in children with SLECTS. In a study of 40 children with centrotemporal spikes with and without seizures compared with 40 healthy controls, patients were significantly impaired in intelligent quotient (IQ), visual perception, short-term memory, and psychiatric status. The deficits in IQ correlated more with the frequency of spikes in the EEG than with the frequency of seizures (183).

A study of 50 children identified educational problems in 54%, developmental learning disability in 38%, expressive language impairment in 18%, and attention disorders in 18% of the cases. The educational problems correlated significantly with the absence of a frontocentral dipole in the EEG (p < 0.001) whereas the abnormal language functions correlated significantly with atypical seizure semiology (p = 0.02) (178). The impact of SLECTS on school performance was demonstrated in another study of 40 cases and controls (123). The patients showed lower scores in academic performance, digits and similarities subtests of WISC, and auditory processing subtests, probably due to executive dysfunction. Impaired social behavior (especially on “theory of mind tasks”) was found in 15 children (65).

Children and adolescents with SLECTS had worse performance on social cognition compared to healthy children as evaluated by Faux-Pas Child Task, which evaluates the recognition and comprehension of other people’s mental state (106).

Language skills. A meta-analysis of 22 studies on literacy and language skills in children with SLECT showed the presence of reading and phonological processing deficits highlighting the need for early literacy and language assessment (157). Atypical evolution of the seizures and a longer duration of epilepsy may influence the language skills of these patients. Thirty-one patients with clinical and electroencephalographic diagnosis of SLECTS and 31 paired normal children underwent a language and neuropsychological assessment performed with several standardized protocols. Findings showed significant dyslexia in patients with SLECTS (129). Risk factors for reading and phonological disorders were evaluated in an observational study of 108 probands with this epileptic syndrome and their 159 siblings: reading disorder was reported in 42% of probands and 22% of siblings (176). Seizure or treatment variables did not appear to be important risk factors for the reading disorder. The association between higher spike-wave index during NREM sleep and poorer nonverbal declarative memory consolidation supported the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation (60).

A systematic review of studies published between 2005 and 2016 on language skills in children with SLECTS concluded that children had language skill disorders in the receptive and productive domains of semantics, morphosyntax, imitations in the intrasyllabic, syllabic, and phonemic levels, and deficits in verbal fluency (semantic and phonemic) and in verbal memory (165). Another systematic review of 43 studies (1179 patients and 1086 healthy controls) on executive functioning in children with SLECTS concluded that children with SLECTS show weaker performances in inhibitory control, cognitive flexibility, and verbal fluency when compared with a control group (142). However, because the quality of evidence was classified as very low, caution is needed when interpreting the strength of the results.

Other problems. Spectral resolution is the ability needed for complex listening tasks, such as understanding speech in the presence of background noise, and has a significant role in children, particularly in classroom learning. A study on the auditory spectral resolution abilities of children with SLECTS using the spectral temporally modulated Ripple test showed that the auditory spectral resolution threshold measured was significantly lower when compared to controls (159).

A study of 74 children with SLECTS showed significant oral dyspraxia in these children as compared to children without epilepsy, particularly in simple and sequenced movements (11). This was attributable to the genetically determined immaturity of cortical structures related to motor planning in children with SLECTS.

A neuropsychological comparative study in 33 recently diagnosed patients with SLECTS and 33 patients with SLECTS after complete remission showed that the newly diagnosed patients with SLECTS exhibited emotion discrimination dysfunction, mainly related to sadness, fear, and disgust, using the Eye Basic Emotion Discrimination Task and the Eye Complex Emotion Discrimination Task (188). This dysfunction was more severe in children with an earlier onset of seizures. However, after epilepsy remission, the ability to discriminate emotions returned to normal.

A study comparing the functional integrity of verbal working memory neural networks in SLECTS with healthy controls using functional magnetic resonance imaging (fMRI) showed that the behavioral performances during working memory tasks, in particular accuracy and response time, were poorer in children with SLECTS than in controls (25).

Central auditory processing disorder was noted in 46% of patients with SLECTS and without intellectual disability, dyslexia, and attention-deficit hyperactivity disorders (117).

Atypical features. The data regarding the prevalence of atypical SLECTS are variable. The atypical clinical features include earlier age of onset of seizures, daytime-only seizures, postictal Todd paresis, prolonged seizures or status epilepticus, focal or opercular status epilepticus, and poor neuropsychological outcomes. Reported atypical EEG findings are unusual spike morphology and distribution, absence-like spike-and-wave discharges, and abnormal background. Atypical features have been noted in up to 50% of the patients with SLECTS (185; 37). In a prospective study of 44 children, 16 children with atypical features were seen in the early EEGs such as slow spike-wave focus, synchronous foci, or generalized 3 Hz spike-wave discharges. This atypical group had significantly lower full-scale IQ and verbal IQ and impairments in certain tasks of the performance scale (118). In a retrospective, multicenter study of 46 patients with atypical features in SLECTS, the predominant manifestations were seizures with affective symptoms (28.2%); seizures with unilateral facial sensorimotor symptoms; oropharyngolaryngeal manifestations; speech arrest with sialorrhea only when awake (24.8%); opercular epileptic status with unilateral or bilateral clonic seizures of the mouth, with speech arrest and sialorrhea when awake and during sleep (15.3%); postictal Todd paralysis after unilateral clonic seizures (15.3%); negative myoclonus (13%); focal sensorimotor seizures characterized by unilateral numbness in the cheeks and one upper limb, additional to unilateral facial clonic seizures, speech arrest, and sialorrhea (2.1%); and sporadic focal tonic-dystonic seizures in the left upper limb only during sleep (2.1%) (61).

Atypical evolution. It is important to discriminate between “atypical features” in children with SLECTS and “atypical evolutions” of SFEC (51; 52). An atypical evolution refers to children with SFEC, including those with centrotemporal spikes, who present with disorders related to continuous spikes and waves during sleep or Landau-Kleffner syndrome. These are associated with severe language and cognitive or behavioral impairments that may be persistent.

The following have been proposed to identify or quantify atypical evolutions:

(1) Early onset of SLECTS, appearance of new seizures such as atypical absences or negative myoclonus, increased frequency of frontocentrotemporal EEG focus in both sleep and wakefulness, and presence of more than five ripples on the centrotemporal spikes are predictive of atypical development (174; 137).

(2) Atypical SLECTS showed more widespread and severe hypometabolism than typical SLECTS, mainly located in the fronto-temporo-parietal cortex (102).

(3) Notable risk factors proposed to predict atypical evolutions are frontotemporal and temporo-parietal localization of epileptic foci, semiology of seizures involving dysarthria, and somatosensory auras in the early presentation of the disease (140).

However, the patients with atypical evolutions account for only around 5% of patients with SLECTS in most of the tertiary epilepsy centers for children.

Prognosis and complications

In general, SLECTS is associated with an excellent prognosis.

Seizures. The majority of the children will have only very infrequent seizures, which are well controlled with the initial antiseizure medication. The prognosis is favorable even for those whose seizures are difficult to control, and seizures almost always remit spontaneously in late adolescence.

Cognitive functions. Most of the children will have normal cognitive functions during the period of active epilepsy and after remission (77). Microstructural changes in cortex and white matter were described in some previous studies, the clinical significance of which is not clear (87; 62).

Moderate to severe language impairment. Moderate to severe language impairment has been reported in some children. The most affected domains were expressive grammar and literacy skills. Persistent deficits in children after the seizure remission suggested possible long-term consequences (124). A comprehensive study of neuropsychological and language profiles of 42 children showed that the patients have normal intelligence and language ability although a specific pattern of difficulties in memory and phonologic awareness was found. No correlation between EEG features and the mentioned impairments was demonstrated (127).

When monitored for at least 2 years, 33 children with a diagnosis of SLECTS showed a higher risk for residual verbal difficulties. Abnormal neuropsychological development was significantly correlated with a greater frequency of NREM sleep discharges, school-aged epilepsy onset, and a higher number of antiepileptic drugs (56).

Attention deficit hyperactivity disorder (ADHD). The prevalence of ADHD may be up to 65%, and patients perform poorer on executive and attentional tasks (105; 36). SLECTS patients with ADHD were found to have significantly thinner superior-inferior frontal cortex, superior temporal cortex, left pericalcarine, and lingual and fusiform cortex compared to healthy controls and a thinner left fusiform cortex compared to SLECTS without ADHD (85). A study of 42 patients with newly diagnosed SLECT evaluated the long-term prognosis of attention deficit in children (over a period of 7 years) and showed that the newly diagnosed patients with SLECTS had an impaired attention network, mainly in the alerting and orienting domains (187). Age of onset, number of seizures, and time of antiepileptic treatment may affect the attention networks. The dysfunction in the attention network was reversed with the remission of SLECTS.

EEG patterns. The presence of atypical interictal epileptiform EEG patterns does not appear to alter prognosis (13). A meta-analysis of 794 patients in 13 cohorts, concluded that the early prediction of seizure outcome in the new patient cannot be made with certainty in SLECTS (16).

Atypical evolutions. Most of the children with atypical evolutions will also have a good long-term prognosis (Aicardi and Chevrie 1982; 55; 53). However, acquired epileptic aphasia and the syndrome of continuous spikes-and-waves during slow sleep have also rarely been associated with SLECTS, along with the risk for permanent language dysfunction or neuropsychologic involvement (49; 53; 54).

EEG activity in this atypical evolution seems to be a kind of secondary bilateral synchrony. In some cases, certain antiepileptic drugs do seem to be associated with this evolution (155; 21; 141).

A Dutch study of epilepsy in childhood included a long-term follow up (12 to 17 years) in 29 children with SLECTS. The authors concluded that both typical and atypical cases had very good prognosis and high remission rates (18).

Antiseizure medication therapy. Antiseizure medication therapy does not necessarily improve and may actually decrease health-related quality-of-life in SLECTS children with low seizure frequency (02).

Transition. SLECTS almost always enters terminal remission before the general age of a planned transition of adolescents (19).

Biological basis

Etiology and pathogenesis

Over the years, our understanding of the genetic basis of SLECTS has significantly evolved. The characteristic centrotemporal pattern in SLECTS was initially considered an autosomal dominant trait with variable penetrance based on monozygotic twin studies (76; 46; 08). Later, a multifactorial pathogenesis of epilepsies with focal epileptiform sharp waves was considered (42). In a multicenter twin collaboration study analysis of the etiology of SLECTS, no concordant twin pairs with the classic form of this syndrome were found in the 18 pairs identified, suggesting that noninherited factors are of major importance in the etiology (172). The atypical evolution of SLECTS may have a more complex inheritance than a simple monogenic pattern (170).

SLECTS has subsequently been linked to chromosome 15q14, terminal deletions of the long arm of chromosome 1q, chromosome 11.p13, polymorphisms in elongator protein complex 4 (ELP4) and brain-derived neurotrophic factor (BDNF), deletions in 16p13, and mutations in GRIN2A, PRRT2, KCNQ2/3, DEPDC5, NR4A2, CHRNA4, ZMYND11RBFOX1/3, and GABRG2) (97; 40; 69; 145; 44; 143; 126; 45; 78; 128).

GRIN2A has been identified as the major gene in epileptic encephalopathies. The role of GRIN2A mutations in SLECTS, especially in severe phenotypes, has been highlighted in recent studies. With the advent of advanced genetic techniques, genome-wide studies are highlighting rare associations of SLECTS with deletions in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, and 20 that overlap with the known autism- and epilepsy-associated candidate genes (82). Similar associations have been seen with multiple single nucleotide polymorphisms in regions on chromosomes 3, 15, and 10 located in or nearby the genes KALRN, CHRNB4, and PTCHD3/RAB18, respectively (154). Environmental risk factors, such as maternal smoking around birth, have also been implicated in the pathogenesis of SLECTS (154). A trios-based whole-exome sequencing study in 28 Chinese patients with typical and atypical SLECTS showed an association with the genes ADGRV1, GRIN2B, and RyR2 (111). As these genes are all calcium homeostasis–associated genes, they suggest a potential effect of calcium homeostasis in the epilepsy.

Pathophysiology. The typical focal, ictal clinical behavior and EEG discharge indicate a disturbance in the sylvian and rolandic areas. SLECTS, Landau-Kleffner syndrome, and continuous spike-and-waves during slow sleep syndrome are often considered as a spectrum of disorders with a common transient, age-dependent, nonlesional, genetically based epileptogenic abnormality, implying the role of a perisylvian epileptic network where the cognitive impairment is caused by epileptic discharges interfering with cognitive development (75).

Electrophysiologic studies, however, fail to demonstrate a discrete generator, and a large, shifting area of dysfunction may be present. In some SLECTS patients, the occurrence of generalized spike-wave EEG discharges, as well as focal spikes in other areas, suggests a relationship between this disorder and the idiopathic generalized epilepsies, as well as with other idiopathic focal epilepsies (99). Around 20% of patients with centrotemporal spikes may also have sharp slow wave complexes in other cortical locations (135). A delayed cortical maturation at the centrotemporal brain regions has been proposed based on the comparison of resting-state brain activities by quantitative electroencephalography in 16 SLECTS patients with clinical seizure remission stage in comparison with healthy controls (156). The study revealed a significantly higher absolute power of the theta and alpha waves in SLECTS patients with clinical seizure remission mainly over the centrotemporal electrodes as opposed to the expected age-related decrease with brain maturation.

Because SLECTS presents during a specific age group when significant diffuse white matter maturation in the brain is going on and has a dramatic activation with non-REM sleep, a role of aberrant thalamo-cortical circuits has been postulated (95). Children with SLECTS have been shown to have delayed brain development, with increased gray matter volume and decreased white matter volume in the rolandic regions, and a 0.45-year delay in brain age in contrast to children with typical development. Delayed brain age has been associated with neuroanatomic changes in the rolandic regions as well as cognitive dysfunction of attention (193). It has been demonstrated that the epileptiform spikes can be triggered and promoted by either a reduced NMDA current or h-type current, and changes in inhibitory transmission in the thalamic reticular nucleus mediate an antagonistic dynamic between epileptiform spikes and spindles in patients with SLECTS (101). A neurodevelopmental origin of SLECTS has been proposed based on a systematic review of MR imaging studies, suggesting that the development of regions of the cortex in children with this epilepsy is abnormal, more widespread, and due to neurodevelopmental delay rather than apparent "damage" from the epilepsy (158).

Patients with atypical evolution of SLECTS show a symmetric hypoperfusion at the level of thalamus in interictal SPECT without structural abnormalities on MRI and increased risk of cognitive deficits (04). A study compared the EEG sleep findings in 30 children with SLECTS with 20 age-matched healthy controls and found significantly lower mean values of the amplitude, duration, and density of the spindle activity in patients with SLECTS (148). Additionally, the risk of epilepsy was found to increase by 1.9% by the decrease of the mean amplitude of the spindles by 1 mV when compared to control group. Overall, these findings suggested an underlying pathophysiologic mechanism for thalamocortical oscillations in SLECTS.

A comparative brain tractography study of 23 children with SLECTS aged 8 to 15 years and age-matched controls showed that children with SLECTS had aberrant development of thalamocortical connectivity to the rolandic cortex, absence of an expected increase in connectivity with age, and persistence of abnormalities over time when observed longitudinally (167).

A study based on cortical morphometry with surface-based morphometry in 25 patients with SLECTS showed that there is aberrant cortical thickness, cortical gyrification, and sulcal depth in areas related to cognitive functions, including language, attention, and memory (104). There was negative correlation between age of onset and cortical thickness and cortical gyrification, as well as between verbal IQ and cortical gyrification in these areas. This correlation between some brain regions and verbal IQ and age of onset provides a potential marker of early neurodevelopmental disturbance and cognitive dysfunction in SLECTS.

A protocol has been proposed for an ongoing multicentric study on the connectome-based predictive modeling for predicting brain age in patients with SLECTS (179). This is a machine-learning approach that uses whole-brain connectivity measured with neuroimaging data ("neural fingerprints") to predict brain-behavior relationships.

Differential diagnosis

Confusing conditions

The presence of the characteristic centrotemporal spikes alone is not diagnostic of epilepsy. Within the susceptible age range, more children will exhibit the characteristic EEG spike pattern without seizures than with seizures. Furthermore, centrotemporal spikes with other morphologic features can be seen in nonepileptic children with diffuse brain disturbances such as cerebral palsy (139) and Rett syndrome (146). SLECTS is the most common epilepsy syndrome, seen in patients with fragile X syndrome, and centrotemporal spikes may be present as an asymptomatic finding (86).

Distinction between SLECTS and structural focal epilepsies, such as mesial temporal lobe epilepsy, can usually be made easily on the basis of history and the unique dipole pattern of the centrotemporal spike. The EEG alone is sufficient to make the diagnosis of SLECTS when nocturnal convulsions are the presenting complaint, and a generalized epileptic syndrome is initially suspected.

Associated or underlying disorders

Because of their prevalence, fortuitous associations may be found between SLECTS and static brain lesions with epilepsy (149). Isolated cases of children with this epileptic syndrome and unilateral opercular neuronal migration disorders have been published (01; 49; 152). Cerebral tumors were reported in five patients (153). Five children with neuronal migration disorders and gliosis were reported as presenting similar to clinical and EEG features of SLECTS. The authors emphasized the role of magnetoencephalography in the differential diagnosis (131). Characteristic spikes of SLECTS were found in 2 of 17 preadolescent children who eventually underwent anteromesial temporal resection for refractory temporal lobe epilepsy due to hippocampal sclerosis and the authors suggested that it might not have been an incidental finding (133).

The pathophysiologic relationships that may exist between SLECTS and other self-limited focal nonrolandic epilepsies can make differential diagnosis difficult. The coexistence of two types of self-limited focal epilepsies in children has been reported, either presenting in sequence one after the other or at the same time (134; 21; 29; 22; 24). The coexistence of childhood absence epilepsy and SLECTS was detected in 11 patients through a systematic record review from eight epilepsy centers (177). A comparison of 17 patients with absence epilepsy and centrotemporal spikes with age-matched 90 children with absence epilepsy showed significantly more global developmental (5 [29%] vs. 5 [6%], P < .009) and expressive language (4 [24%] vs. 5 [6%], P < .034) delay, and more difficulties with school performance (11 [65%] vs. 32 [36%], P < .025), especially with language-related tasks (6 [35%] vs. 5 [6%], P < .001) in children with absence epilepsy and centrotemporal spikes (38). The latter may be a marker of additional cognitive challenges for the physicians.

Finally, another interesting association to consider is with migraine in patients with SLECTS (14). In a comparative cohort of children with SLECTS, with cryptogenic/symptomatic partial epilepsy and with no history of seizures (n = 53 each), a higher rate of migraine was identified in focal epilepsy, regardless of the etiology (186). Another study of 72 children with SLECTS and their siblings showed that prevalence of migraine was 15% in epilepsy probands versus 7% in nonepileptic controls (26). Prevalence of migraine was 14% in siblings of SLECTS and 4% in siblings of controls.

Diagnostic workup

EEG. The defining feature of the syndrome of SLECTS is the presence of centrotemporal spikes on interictal EEG. EEG background will be normal for the age.

Characteristics of EEG spikes in SLECTS
	• Broad, diphasic, high-voltage (100 to 300 microvolts) spikes, with a transverse dipole, and they are often followed by a slow wave.
	• The spikes may occur isolated or in clusters, with a rhythm of about 1.5 to 3 Hz.
	• Focal rhythmic slow activity is occasionally observed in the region where the spikes are seen (122).
	• Generalized 3 Hz spike-and-waves and focal spikes in other brain areas may also be seen in a minority of children (13).
	• The centrotemporal spikes are not enhanced by eye opening or closure, by hyperventilation, or by photic stimulation. Hyperventilation may even reduce the frequency of rolandic spikes (181).
	• The spike rate is increased in drowsiness and in all stages of sleep, and in about one third of children, the spikes appear only in sleep (114).
	• The sleep EEG organization is preserved (33). In spite of their increasing frequency during sleep, the centrotemporal spikes show the same morphology as during wakefulness.
	• A change in morphology, particularly the appearance of focal fast spikes or polyspikes, or a marked increase in the slow component, or a brief depression of voltage may suggest the possibility of a focal lesion (35).
	• There is no correlation between the burden of spike discharges in the EEG and frequency, length, or duration of clinical seizures (98). In fact, extreme discrepancies between the rarity of seizures and the activity of the EEG foci are not uncommon, and clinical experience indicates that the EEG is often relatively unchanged, even with effective treatment (06).
Dipolar pattern in SLECTS
	• Several authors emphasized the characteristic dipolar pattern in the EEG (70; 108; 171).
	• According to EEG findings, two groups of patients have been noted (maximal negativity was registered in high- and low-central regions, but never in midtemporal regions): a high-central region group with more frequent hand involvement and the low-central group with common orofacial symptoms.
	• Electroencephalographic spike source dipoles of centrotemporal spikes were analyzed in 37 patients (88). Differences in spike source dipole were found in patients showing atypical outcomes.
Newer techniques for EEG analysis
	• An algorithm for automatic classification of centrotemporal spikes in the interictal EEG according to the epilepsy type has been proposed that may distinguish benign from symptomatic causes (120).
	• Spike ripples have been identified as a promising new biomarker of epilepsy in noninvasive EEG studies (57). Ripples on centrotemporal spikes are considered to indicate epilepsy severity. The absence of ripples predicts a relatively benign clinical entity (174). A study proposed that spike ripples (ripples cooccurring with epileptiform discharges) have a comparable sensitivity and negative predictive value but greater specificity and positive predictive value as compared to spikes alone in predicting seizure risk in children with SLECTS (91). In a comparative study between seven patients with atypical SLECTS and 18 patients with typical SLECTS in the secondary bilateral synchrony and nonsecondary bilateral synchrony periods, it was found that ripples were enhanced when interictal epileptiform discharges were bilaterally synchronized in patients with atypical SLECTS (80). The study highlighted the distinction between atypical from typical SLECTS with ripple distribution in the nonsecondary bilateral synchrony period.
	• Intrahemispheric cortico-cortical EEG functional connectivity (EEGfC) was explored in 17 non-medicated children with SLECTS and 19 controls, and the areas of increased EEGfC corresponded to cortical areas related to speech and attention deficits (27).
	• A nonlinear analysis, including measures such as multiscale entropy and recurrence quantitative analysis, of visually normal EEGs has been used to differentiate between patients with and without SLECTS (150).
	• A novel machine-learning model that efficiently distinguished rolandic seizures from normal EEG signals has been proposed, with an accuracy exceeding 97.6% (116). This proposed machine-learning model processes the identification procedure in the following order: (1) creating preliminary EEG features using signal empirical mode decomposition, (2) applying weighted overlook graph, and (3) classifying the results through a 2-dimensional convolutional neural network.
	• A novel SLECTS spike detection algorithm based on time domain EEG sequence features and the long short-term memory neural network has been proposed to aid in the automated detection of rolandic spikes, with a sensitivity of 92.04% and precision of 85.75% (191).

Spike clearance velocity. Spike clearance velocity (defined as a decrease in the spike-wave rate over time in 4-year sequential follow-up EEGs) has also been suggested as an EEG marker to guide antiseizure medications in children with SLECTS (166). The study assessed the spike characteristics and temporal spike evolution on serial EEGs of children with SLECTS treated with antiseizure medications. The study cohort consisted of 127 children with SLECTS divided into three groups based on antiseizure medication responsiveness: group I was seizure-free with monotherapy (n: 61, 48%); group II was seizure-controlled with monotherapy (n: 52, 41%); and group III was seizure-controlled with dual therapy (n: 14, 11%). The clinical profiles and sequential 4-year follow-up visual EEG recordings of the children were evaluated. Each EEG was reanalyzed with three spike characteristics on the epochs: (1) spike-wave rate, (2) spike topography, and (3) spike localization. The spike clearance velocity, defined as a decrease in the spike-wave rate over time in 4-year sequential follow-up EEGs, was calculated. The authors found no statistical significance across the study groups with respect to initial EEG spike characteristics (spike-wave rate, spike localization, and spike topography). However, the spike clearance velocity was significantly slower in group III than in group I in 4-year sequential follow-up EEGs. Further, the spike clearance velocity was not different across the antiseizure medication groups (oxcarbazepine, valproic acid, and levetiracetam).

Magnetoencephalographic analysis. Magnetoencephalography of generator and propagation of centrotemporal spikes in SLECTS with neuromagnetic 3-dimensional dipole localization suggested that these discharges are generated through a mechanism similar to that of somatosensory evoked responses (119). An MEG-based study of 33 children with SLECTS and 18 healthy children to explore the pathophysiological mechanism of cognitive function changes in early untreated children showed magnetic source inactivation of the medial frontal cortex and posterior cingulate cortex regions during the interictal time, possibly accounting for the cognitive decline in early untreated children with SLECTS (103). The magnetic source localization in the 4 to 8 Hz frequency band may be a new imaging marker for the diagnosis of new SLECTS.

MRI brain. A few cases have been noted to have focal cortical dysplasia and even tumors after presenting with the clinical and EEG phenotype of SLECTS (01; 49; 153; 152). In 171 consecutive patients with this syndrome studied with CT or MRI, 10 children were noted to have neuroimaging abnormalities (64). Frontal and prefrontal volumes revealed growth disturbances in the patients with cognitive impairments (180).

Positron emission tomography. Positron emission tomography is not routinely performed in these children. PET might be helpful to distinguish SLECTS from symptomatic cases of focal epilepsy in children (173). Focal cortical hypermetabolism in the central cortex was noted in three children with atypical SLECTS during the seizure-free period (30), suggesting a localized, increased cortical activity, likely due to either subclinical seizure activity or “active” inhibitory (GABAergic) processes.

Functional MRI (fMRI). Several fMRI studies have been reported in SLECTS. Volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus were studied in a group of 13 children with recent-onset SLECTS and 54 healthy controls (107). Aberrant functional connectivity between motor and language networks were found in 23 children with rolandic epilepsy studied with fMRI (12). A “granger causality density” method has been proposed as an effective and reliable neuroimaging biomarker to localize the interictal focus of SLECTS and make an early diagnosis (32). Resting state fMRI studies in a smaller number of patients with SLECT (n=12) show normal cortical-subcortical functional connectivity with compensatory hyperconnectivity between cortical networks caused by widespread cortical abnormal discharges and might account for the self-limited clinical outcome in SLECTS (58). Another fMRI study of 26 children with SLECTS to measure intrinsic brain activity showed aberrant dynamic regional coherence in sensorimotor, linguistic, and lateral temporal regions, suggesting that there is an intrinsic dynamic mechanism or interplay that underlies cognitive performance in these children (83).

Transcranial magnetic stimulation. A pilot study proposed the use of transcranial magnetic stimulation paired with EMG and EEG to measure the trajectory of cortical excitability in children with SLECTS and to assess whether motor cortex plasticity correlates with learning ability (09). Resting state functional MRI analysis has shown an association between centrotemporal spikes and earlier hemodynamic activations in epileptogenic regions in SLECTS that were counteracted by levetiracetam treatment (190).

Other investigational techniques. Seizure occurs when the balance between excitatory and inhibitory inputs to neurons is perturbed, resulting in abnormal electrical activity. Based on this, a study showed that an existing excitatory and inhibitory imbalance in neural networks is a useful diagnostic biomarker for SLECTS using a resting-state dynamic causal modeling-based support vector machine (rs-DCM-SVM) algorithm, with an accuracy of 81% to 88% (31). This multicenter study enrolled a discovery cohort (76 children with rolandic epilepsy and 76 normal controls) and a replication cohort (59 children with rolandic epilepsy and 60 normal controls). Spatial independent component analysis was used in seven canonical neural networks, and a total of 25 regions of interest were selected from these networks. The rs-DCM-SVM classifier was used for individual classification, consensus feature selection, and feature ranking.

Management

	• SLECTS is an age-related syndrome that almost always disappears by adulthood, regardless of age at onset; therefore, excessive restriction of activities and overprotection of affected children are not advised.
	• Drug therapy is necessary only if there are very frequent seizures.
	• Monotherapy should be used whenever possible.
	• Focal motor seizures, a short interval between the first and second attack, and an early onset usually indicate the necessity of treatment.
	• Carbamazepine and valproic acid were traditionally the drugs of choice for this syndrome. Levetiracetam monotherapy has gained attention as a probable alternative. A systematic review of seizure-freedom rates in patients with SLECTS receiving antiepileptic drugs suggested the use of sulthiame, levetiracetam, or clobazam as first-line agents for the treatment of SLECTS in children (66).
	• Current data are insufficient to make firm recommendations as most of the studies include a very small number of patients, with limited head-to-head comparisons.

Antiseizure medication treatment

In a comparative trial on 56 patients with SLECTS, 33 children received levetiracetam and 23 received valproic acid as initial monotherapy (189). The seizure-freedom rates were not significantly different between the two groups. A greater number of the children taking valproic acid achieved EEG normalization compared to those taking levetiracetam (95% vs. 72% at 18 months). The authors concluded that low-dosage valproic acid and levetiracetam monotherapy are equally effective in controlling seizures but valproic acid exhibited better efficacy than levetiracetam in improving the electrophysiological abnormalities.

In another study, 89 patients were treated with carbamazepine, 73 patients with valproic acid, and 35 patients with levetiracetam (84). Responders comprised 11.2% of the patients treated with carbamazepine, 56.2% of the patients with valproic acid, and 71.4% of the patients with levetiracetam.

A meta-analysis of 49 studies from 2000 to 2018 suggested that levetiracetam, as an initial antiepileptic drug, was superior to carbamazepine for cognitive protection (07). Levetiracetam inhibited centrotemporal spikes-associated activation intensity and altered its temporal pattern. It also affected the brain deactivation related to higher cognition networks (194). Another study compared the changes in the cognitive profile of 20 children with SLECTS on levetiracetam monotherapy (dose range 500-1750 mg/d) and 10 children with specific learning disabilities (130). Children administered levetiracetam showed a mild but statistically significant improvement in overall cognitive abilities. Verbal skills, visual-perceptual reasoning, working memory, and processing speed showed slight but significant improvement as compared to the control group at 2-year follow-up.

Oxcarbazepine monotherapy was found to be more effective and associated with higher improvements in intelligence and cognitive function than levetiracetam monotherapy in children with SLECTS (161). A multicentric study of 1817 Chinese children demonstrated that oxcarbazepine, levetiracetam, and valproic acid could be used as first-line drugs, and the efficacy of oxcarbazepine and levetiracetam was higher than that of valproic acid (110). In a retrospective study of 430 patients with centrotemporal spikes, the comparative efficacy of levetiracetam, oxcarbazepine, and valproic acid was evaluated over a 2-year follow-up (72). There was no significant difference in EEG results, number of status epilepticus events, atypical features, or recurrence rates.

Benzodiazepine treatment for several weeks was also recommended (39). In comparison with valproate and carbamazepine, clonazepam showed to be more efficient in making rolandic discharges disappear after 4 weeks of treatment (121). The use of clobazam at night may be considered in those children who only have seizures during sleep (50). A prospective controlled study of clobazam versus carbamazepine in patients with frequent seizure episodes showed that clobazam in monotherapy was as effective as carbamazepine and better tolerated (03).

Sulthiame was recommended in several reports (41; 100). In a double-blind, placebo-controlled study of 66 children, sulthiame was found to be remarkably effective in preventing seizures and was well tolerated (144). It has been considered as the drug of choice in patients presenting with atypical evolutions associated to secondary bilateral synchronies in the EEG (53; 50). A noninferiority study comparing levetiracetam to sulthiame performed in 43 patients with SLECTS showed that the rates of seizure-free patients were relatively high in both groups, although the results indicated that termination of drug treatment due to seizure recurrence or adverse events occurred more frequently in the levetiracetam group compared to sulthiame group (15). Another randomized controlled trial to compare the effects of levetiracetam and sulthiame on EEG in 43 children with SLECTS showed similar reductions in the spike-wave-index with both the drugs. Persistent EEG abnormalities in both the groups were associated with treatment failures (162).

In a monotherapy trial of topiramate (109), the drug was orally administrated once a night (2 mg/kg/day) and twice a day (4 mg/kg/day) in 85 patients with SLECTS. There was no significant difference in overall efficacy rate or changes in EEG activity between the two groups but the rate of adverse reactions for night dose was significantly lower than daytime dosing group, suggesting the former as a feasible strategy for the treatment of SLECTS.

In a retrospective study of 120 patients who were randomly treated with lamotrigine, oxcarbazepine, or topiramate monotherapy and underwent EEG and standardized language tests, it was noted that the seizure recurrence rates were 19.4% with lamotrigine, 21.7% with topiramate, and 11.4% with oxcarbazepine. Overall, the improvements in language and problem-solving performance in children with SLECTS were greater for lamotrigine and oxcarbazepine than for topiramate (74).

As the seizures will almost invariably disappear in adolescence, therapy beyond that period is of little value. Relapse of seizures, however, may occur after premature antiepileptic drug withdrawal. Studies suggest that the antiepileptic drugs can control the seizures but they neither improve the interictal EEG significantly nor shorten the years of spike persistence (89). Young age of seizure onset correlated with longer duration of EEG abnormalities (96). Pattern of spike disappearance did not significantly differ between the medication naïve group and antiepileptic drug-treated group (73).

In a retrospective analysis of initial antiepileptic drug treatment in 84 children with this epilepsy syndrome, it was shown that 14% of the children continued to have seizures after initial antiseizure medication treatment (81). Multivariate analysis suggested that younger age of seizure onset was the independent risk factor, predicting a poor response to initial antiseizure medication treatment. In a retrospective study to identify risk factors associated with poor response to initial antiseizure medication therapy in 57 with SLECTS, 28% experienced poor responses, and predicting factors included onset of seizures prior to the age of 5 years and history of febrile seizures (138).

Nonpharmacological treatment

Auditory stimulation during non-REM sleep suppresses spike activity and has been proposed as a nonpharmacological treatment of SLECTS (90). Further studies are needed before this technique can be implemented in clinical practice.

Outcomes

Overall, the long-term seizure outcome seems to be excellent, with less than 2% of cases developing absence seizures or generalized tonic-clonic seizures in adult life. Adults who had recovered from SLECTS were also not found to have negative outcomes in the fields of development, education, employment, and social adaptation (20).

However, children with SLECTS display variable diffuse cognitive deficits consistent with widespread cortical dysfunction.

A systematic review and meta-analysis of 42 studies published prior to 2016 on cognitive functioning in children with SLECTS concluded that children with SLECTS demonstrated significantly lower scores on neuropsychological tests across all cognitive factors compared to healthy controls (184). However, the possibility of a publication bias cannot be ruled out. The adverse cognitive outcome may not be affected by the number of interictal epileptiform discharges in patients with SLECTS (169). An observational cross-sectional study showed that the mean cognitive and neuropsychological performances were adequate overall 5 years after seizure remission, except for the dictation (175).

A natural history study of children with SLECTS from a large, prospective, longitudinal cohort reported a high incidence of ADHD symptoms (18.3%) or learning difficulties (21.7%) before the diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after the diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls (147). A systematic review of nine case-control and cohort studies on ADHD and ADHD-related neural networks in SLECTS showed that the reported prevalence of ADHD in patients with SLECTS was around 60% (05). Early age of seizure onset, long course of disease, and low intelligence scores were found in a cohort of SLECTS with comorbid ADHD (79). Comorbid ADHD has been associated with a higher degree of impairment in some domains of intellect (48).

A small Swedish study indicated residual deficits in dichotic listening (verbal perception) and oromotor performance in young adults with SLECTS when followed up for 10 years (168).

Sudden unexpected death in epilepsy is a very rare outcome in SLECTS and has been reported in three children with this syndrome among 189 decedents enrolled in the North American Sudden Unexpected Death in Epilepsy Registry (43). This seems to be an intriguing observation that needs further validation.

References

01: Ambrosetto G. Unilateral opercular macrogyria and benign childhood epilepsy with centrotemporal (rolandic) spikes. Epilepsia 1992;33:499-503. PMID 1592027
02: An O, Nagae LM, Aringazina A, Winesett SP. Comparative assessment of health-related quality of life with and without anticonvulsant therapy in patients with childhood epilepsy with centrotemporal spikes. J Int Med Res 2021;49(8):3000605211039805. PMID 34459274
03: Andrade R, García-Espinosa A, Machado-Rojas A, García-González ME, Trápaga-Quincoses O, Morales-Chacón LM. [A prospective, open, controlled and randomised study of clobazam versus carbamazepine in patients with frequent episodes of Rolandic epilepsy.] Rev Neurol 2009;49(11):581-6. PMID 19921623
04: Andrade-Machado R. Benign epilepsy with centro temporal spikes: Is there a thalamocortical network dysfunction present? Adding supporting evidence from SPECT imaging. Seizure 2020;80:143-4. PMID 32570171
05: Arico M, Arigliani E, Giannotti F, Romani M. ADHD and ADHD-related neural networks in benign epilepsy with centrotemporal spikes: a systematic review. Epilepsy Behav 2020;112:107448. PMID 32916583
06: Arzimanoglou A, Guerrini R, Aicardi J. Epilepsies characterized by partial seizures. In: Arzimanoglou A, Guerrini R, Aicardi J, editors. Aicardi´s epilepsy in children. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2004;114-75.
07: Asadi-Pooya AA, Forouzesh M, Eidi H, Mirzaghafour SE. Levetiracetam versus carbamazepine in treatment of rolandic epilepsy. Epilepsy Behav 2019;94:1-8. PMID 30884401
08: Bali B, Kull LL, Strug LJ, et al. Autosomal dominant inheritance of centrotemporal sharp waves in rolandic epilepsy families. Epilepsia 2007;48(12):2266-72. PMID 17662063
09: Baumer FM, Pfeifer K, Fogarty A, et al. Cortical excitability, synaptic plasticity, and cognition in benign epilepsy with centrotemporal spikes: a pilot TMS-EMG-EEG study. J Clin Neurophysiol 2020;37(2):170-80. PMID 32142025
10: Beaussart M. Benign epilepsy of children with rolandic (centrotemporal) paroxysmal foci. Epilepsia 1972;13:795-811. PMID 4509173
11: Bernardo HNSA, Miziara C, de Manreza MLG, Mansur LL. Oral dyspraxia in self-limited epilepsy with centrotemporal spikes: a comparative study with a control group. Arq Neuropsiquiatr 2021;79(12):1076-83. PMID 34816971
12: Besseling RM, Overvliet GM, Jansen JF, et al. Aberrant functional connectivity between motor and language networks in rolandic epilepsy. Epilepsy Res 2013;107(3):253-62. PMID 24210960
13: Beydoun A, Garofalo EA, Drury I. Generalized spike-waves, multiple loci, and clinical course in children with EEG features of benign epilepsy of childhood with centrotemporal spikes. Epilepsia 1992;33:1091-6. PMID 1464269
14: Bladin PF. The association of benign rolandic epilepsy with migraine. In: Andermann F, Lugaresi E, editors. Migraine and Epilepsy. Boston: Butterworths, 1987:145-52.
15: Borggraefe I, Bonfert M, Bast T, et al. Levetiracetam vs. sulthiame in benign epilepsy with centrotemporal spikes in childhood: a double-blinded, randomized, controlled trial (German HEAD Study). Eur J Paediatr Neurol 2013;17(5):507-14. PMID 23642492
16: Bouma PA, Bovenkerk AC, Westendorp RG, Brouwer OF. The course of benign partial epilepsy of childhood with centrotemporal spikes: a meta-analysis. Neurology 1997;48(2):430-7. PMID 9040734
17: Bray PF, Wiser WC. Evidence for a genetic etiology of temporal central abnormalities in focal epilepsy. N Engl J Med 1964;271:926-33. PMID 14197414
18: Callenbach PM, Bouma PA, Geerts AT, et al. Long term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch Study of Epilepsy in Childhood. Seizure 2010;19(8):501-6. PMID 20688544
19: Camfield CS, Berg A, Stephani U, Wirrell EC. Transition issues for benign epilepsy with centrotemporal spikes, nonlesional focal epilepsy in otherwise normal children, childhood absence epilepsy, and juvenile myoclonic epilepsy. Epilepsia 2014;55 Suppl 3:16-20. PMID 25209080
20: Camfield CS, Camfield PR. Rolandic epilepsy has little effect on adult life 30 years later: a population-based study. Neurology 2014;82(13):1162-6. PMID 24562059
21: Caraballo R, Cersosimo R, Fejerman N. Idiopathic partial epilepsies with rolandic and occipital spikes appearing in the same children. J Epilepsy 1998;11:261-64.
22: Caraballo RH, Aldao Mdel R, Cachia P. Benign childhood seizure susceptibility syndrome: three case reports. Epileptic Disord 2011;13(2):133-9. PMID 21628136
23: Cavazzuti GB. Epidemiology of different types of epilepsy in school age children of Modena, Italy. Epilepsia 1980;21:57-62. PMID 6766394
24: Cerminara C, Coniglio A, El-Malhany N, Casarelli L, Curatolo P. Two epileptic syndromes, one brain: Childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. Seizure 2012;21(1):70-4. PMID 22000044
25: Ciumas C, Montavont A, Ilski F, et al. Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes. Neuroimage Clin 2020;8:102392. PMID 32927234
26: Clarke T, Baskurt Z, Strug LJ, Pal DK. Evidence of shared genetic risk factors for migraine and rolandic epilepsy. Epilepsia 2009;50(11):2428-33. PMID 19674062
27: Clemens B, Puskás S, Spisák T, et al. Increased resting-state EEG functional connectivity in benign childhood epilepsy with centro-temporal spikes. Seizure 2016;35:50-5. PMID 26794010
28: Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30(4):389-99. PMID 2502382
29: Covanis A, Lada C, Skiadas K. Children with Rolandic spikes and ictal vomiting: Rolandic epilepsy or Panayiotopoulos syndrome. Epileptic Disorders 2003;5(3):139-43. PMID 14684348
30: Curnow SR, Vogrin SJ, Barton S, Bailey CA, Harvey AS. Focal cortical hypermetabolism in atypical benign rolandic epilepsy. Epilepsy Res 2020;161:106288. PMID 32086099
31: Dai XJ, Liu H, Yang Y, Wang Y, Wan F. Brain network excitatory/inhibitory imbalance is a biomarker for drug-naive Rolandic epilepsy: a radiomics strategy. Epilepsia 2021a;62(10):2426-38. PMID 34346086
32: Dai XJ, Yang Y, Wang N, Tao W, Fan J, Wang Y. Reliability and availability of granger causality density in localization of Rolandic focus in BECTS. Brain Imaging Behav 2021b;15(3):1542-52. PMID 32737823
33: Dalla Bernardina B, Beghini G. Rolandic spikes in children with and without epilepsy. Epilepsia 1976;17:161-7. PMID 947746
34: Dalla Bernardina B, Sgro V, Fejerman N. Epilepsy with centrotemporal spikes and related syndromes. In: Roger J, Bureau M, Dravet Ch, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence, 3rd ed. Eastleigh UK: John Libbey & Co Ltd, 2002:181-202.
35: Dalla Bernardina B, Sgro V, Fejerman N. Epilepsy with centrotemporal spikes and related syndromes. In: Roger J, Bureau M, Dravet Ch, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence, 4th ed. Montrouge UK: John Libbey & Co Ltd, 2005:203-25.
36: Danhofer P, Pejčochová J, Dušek L, Rektor I, Ošlejšková H. The influence of EEG-detected nocturnal centrotemporal discharges on the expression of core symptoms of ADHD in children with benign childhood epilepsy with centrotemporal spikes (BCECTS): a prospective study in a tertiary referral center. Epilepsy Behav 2018;79:75-81. PMID 29253678
37: Datta A, Sinclair DB. Benign epilepsy of childhood with rolandic spikes: typical and atypical variants. Pediatr Neurol 2007;36(3):141-5. PMID 17352945
38: Datta AN, Wallbank L, Mak JCH, Wong PKH. Clinical significance of incidental rolandic spikes in children with absence epilepsy. J Child Neurol 2019;34(11):631-8. PMID 31113278
39: De Negri M, Baglietto MG, Gaggero R. Benzodiazepine (BDZ) treatment of benign childhood epilepsy with centrotemporal spikes. Brain Dev 1997;19(7):506. PMID 9408602
40: Dimassi S, Labalme A, Lesca G, et al. A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2. Epilepsia 2014;55(2):370-8. PMID 24372385
41: Doose H, Baier WK, Ernst JP, Tuxhorn I, Volzke E. Benign partial epilepsy: treatment with sulthiame. Dev Med Child Neurol 1988;30:683-4. PMID 2906619
42: Doose H, Brigger-Heuer B, Neubauer B. Children with focal sharp waves: clinical and genetic aspects. Epilepsia 1997;38(7):788-96. PMID 9579906
43: Doumlele K, Friedman D, Buchhalter J, Donner EJ, Louik J, Devinsky O. Sudden unexpected death in epilepsy among patients with benign childhood epilepsy with centrotemporal spikes. JAMA Neurol 2017;74(6):645-9. PMID 28384699
44: Dryzalowski P, Jozwiak S, Franckiewicz M, Strzelecka J. Benign epilepsy with centrotemporal spikes - current concepts of diagnosis and treatment. Neurol Neurochir Pol 2018;52(6):677-89. PMID 30219586
45: Duan Y, Leng X, Liu C, et al. The correlation of ELP4-PAX6 with rolandic spike sources in idiopathic rolandic epilepsy syndromes. Front Neurol 2021;12:643964. PMID 33897599
46: Eeg-Olofsson O. Further genetic aspects in benign localized epilepsies in early childhood. In: Degen R, Dreifuss FE, editors. Benign localized and generalized epilepsies of early childhood. Epilepsy Research. Suppl 6. Amsterdam: Elsevier, 1992:117-9.
47: Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42(6):796-803. PMID 11422340
48: Fang HB, Wang R, Chu LN, Feng YF, Bai RR, Guo FT. Cognitive impairment in children with benign childhood epilepsy with centrotemporal spikes and attention deficit hyperactivity disorder: a prospective study. Zhongguo Dang Dai Er Ke Za Zhi 2021; 23(8):791-6. PMID 34511167
49: Fejerman N. Atypical evolutions of benign partial epilepsies in children. Int Pediatr 1996;11(6):351-6.
50: Fejerman N. Benign focal epilepsies in infancy, childhood and adolescence. Rev Neurol 2002;34(1):7-18. PMID 11988887
51: Fejerman N. Benign childhood epilepsy with centrotemporal spikes. In: Engel J, Pedley TA, editors. Epilepsy: A Comprehensive Textbook. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2008:2369-78.
52: Fejerman N. Atypical rolandic epilepsy. Epilepsia 2009;50 Suppl 7:9-12. PMID 19682042
53: Fejerman N, Caraballo R, Tenembaum SN. Atypical evolutions of benign localization-related epilepsies in children: are they predictable. Epilepsia 2000;41(4):380-90. PMID 10756401
54: Fejerman N, Caraballo RH, Dalla Bernardina B. Benign childhood epilepsy with centrotemporal spikes. In: Fejerman N, Caraballo RH, editors. Benign focal epilepsies in infancy, childhood and adolescence. Montrouge: John Libbey, 2007:77-113.
55: Fejerman N, Di Blasi AM. Status epilepticus of benign partial epilepsies in children: report of two cases. Epilepsia 1987;28:351-5. PMID 3113924
56: Filippini M, Boni A, Giannotta M, Gobbi G. Neuropsychological development in children belonging to BECTS spectrum: long-term effect of epileptiform activity. Epilepsy Behav 2013;28(3):504-11. PMID 23896351
57: Frauscher B, Bartolomei F, Kobayashi K, et al. High-frequency oscillations: the state of clinical research. Epilepsia 2017;58(8):1316-29. PMID 28666056
58: Fu C, Aisikaer A, Chen Z, Yu Q, Yin J, Yang W. Different functional network connectivity patterns in epilepsy: a rest-state fMRI study on mesial temporal lobe epilepsy and benign epilepsy with centrotemporal spike. Front Neurol 2021;12:668856. PMID 34122313
59: Fusco L, Trivisano M, Specchio N, Vigevano F. Rolandic epilepsy: an uncommon presentation with leg motor seizures. Epilepsia 2010;51(12):2488-91. PMID 21204813
60: Galer S, Urbain C, De Tiège X, et al. Impaired sleep-related consolidation of declarative memories in idiopathic focal epilepsies of childhood. Epilepsy Behav 2015;43:16-23. PMID 25546732
61: Galicchio S, Espeche A, Cersosimo R, et al. Self-limited epilepsy with centro-temporal spikes: a study of 46 patients with unusual clinical manifestations. Epilepsy Res 2021;169:106507. PMID 33296810
62: Garcia-Ramos C, Jackson DC, Lin JJ, et al. Cognition and brain development in children with benign epilepsy with centrotemporal spikes. Epilepsia 2015;56(10):1615-22. PMID 26337046
63: Gastaut Y. Un element deroutant de la semeiologie electroencephalographique: les pointes prerolandiques sans signification focale. Rev Neurol (Paris) 1952;87:488-90.
64: Gelisse P, Corda D, Raybaud C, Dravet C, Bureau M, Genton P. Abnormal neuroimaging in patients with benign epilepsy with centrotemporal spikes. Epilepsia 2003;44(3):372-8. PMID 12614393
65: Genizi J, Shamay-Tsoory SG, Shahar E, Yaniv S, Aharon-Perez J. Impaired social behavior in children with benign childhood epilepsy with centrotemporal spikes. J Child Neurol 2012;27(2):156-61. PMID 21868370
66: Gerstl L, Willimsky E, Remi C, Noachtar S, Borggrafe I, Tacke M. A systematic review of seizure-freedom rates in patients with benign epilepsy of childhood with centrotemporal spikes receiving antiepileptic drugs. Clin Neuropharmacol 2021;44(2):39-46. PMID 33605607
67: Gibbs EL, Gibbs FA. Good prognosis of mid-temporal epilepsy. Epilepsia 1960;1:448-53. PMID 13827913
68: Gibbs EL, Gillen HW, Gibbs FA. Disappearance and migration of epileptic foci in childhood. Am J Dis Child 1954;88:596-603. PMID 13206379
69: Gkampeta A, Fidani L, Clarimón J, et al. Association of brain-derived neurotrophic factor (BDNF) and elongator protein complex 4 (ELP4) polymorphisms with benign epilepsy with centrotemporal spikes in a Greek population. Epilepsy Res 2014;108(10):1734-9. PMID 25301525
70: Gregory DL, Wong PK. Topographical analysis of the centrotemporal discharges in benign Rolandic epilepsy of childhood. Epilepsia 1984;25:705-11. PMID 6510378
71: Guerrini R, Pellacani S. Benign childhood focal epilepsies. Epilepsia 2012;53 Suppl 4:9-18. PMID 22946717
72: Gu W, Chen J, Tian W, et al. Outcome analysis of children with rolandic discharges on EEG: a real-world study. Seizure 2020;82:105-8.** PMID 33059311
73: Han JY, Choi SA, Chung YG, et al. Change of centrotemporal spikes from onset to remission in self-limited epilepsy with centrotemporal spikes (SLECTS). Brain Dev 2020;42(3):270-6. PMID 31813543
74: Han MJ, Kim SJ. Effects of antiepileptic drugs on language abilities in benign epilepsy of childhood with centrotemporal spikes. J Clin Neurol 2018;14(4):523-9. PMID 30198231
75: Halasz P, Kelemen A, Clemens B, et al. The perisylvian epileptic network. A unifying concept. Ideggyogy Sz 2005;58(3-4):104. PMID 15884395
76: Heijbel J, Blom S, Rasmuson M. Benign epilepsy of childhood with centrotemporal EEG foci: a genetic study. Epilepsia 1975;16:285-93. PMID 807473
77: Hommet C, Billard C, Motte J, et al. Cognitive function in adolescents and young adults in complete remission from benign childhood epilepsy with centro-temporal spikes. Epileptic Disord 2001;3(4):207-16. PMID 11844716
78: Hu X, Tang J, Hua Y, Wang Y, Huang J. Evaluation of candidate genes in a Chinese cohort of atypical Rolandic epilepsy. Epileptic Disord 2021;23(4): 623-32. PMID 34279234
79: Huang C, Hu W, Tan G, Xu Y, Liu L. Clinical and electroencephalographic features of benign childhood epilepsy with centrotemporal spikes comorbidity with attention-deficit hyperactivity disorder in Southwest China. Epilepsy Behav 2021;111:107240. PMID 32603807
80: Ikemoto S, Hamano SI, Yokota S, Koichihara R, Hirata Y, Matsuura R. Enhancement and bilateral synchronization of ripples in atypical benign epilepsy of childhood with centrotemporal spikes. Clin Neurophysiol 2018;129(9):1920-5. PMID 30005220
81: Incecik F, Altunbasak S, Herguner OM, Mert G, Sahan D. Prognostic significance of failure of the initial antiepileptic drug in children with benign childhood epilepsy with centrotemporal spikes. Brain Dev 2015;37(1):66-70. PMID 24657010
82: Jabbari K, Bobbili DR, Lal D, et al. Rare gene deletions in genetic generalized and Rolandic epilepsies. PLoS One 2018;13(8):e0202022. PMID 30148849
83: Jiang L, Ma X, Liu H, et al. Aberrant dynamics of regional coherence measured by resting-state fMRI in children with benign epilepsy with centrotemporal spikes (BECTS). Front Neurol 2021;12:712071. PMID 34975706
84: Kanemura H, Sano F, Ohyama T, Aihara M. Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy. Seizure 2018;62:79-83. PMID 30308427
85: Karalok ZS, Ozturk Z, Gunes A. Cortical thinning in benign epilepsy with centrotemporal spikes (BECTS) with or without attention-deficit/hyperactivity (ADHD). J Clin Neurosci 2019;68:123-7. PMID 31326285
86: Kidd SA, Lachiewicz A, Barbouth D, et al. Fragile X syndrome: a review of associated medical problems. Pediatrics 2014;134(5):995-1005. PMID 25287458
87: Kim SE, Lee JH, Chung HK, Lim SM, Lee HW. Alterations in white matter microstructures and cognitive dysfunctions in benign childhood epilepsy with centrotemporal spikes. Eur J Neurol 2014;21(5):708-17. PMID 24330132
88: Kim H, Yoo IH, Lim BC, et al. Averaged EEG spike dipole analysis may predict atypical outcome in benign childhood epilepsy with centrotemporal spikes (BCECTS). Brain Dev 2016;38(10):903-8. PMID 27329010
89: Kim H, Kim SY, Lim BC, et al. Spike persistence and normalization in benign epilepsy with centrotemporal spikes - implications for management. Brain Dev 2018;40(8):693-8. PMID 29754875
90: Klinzing JG, Tashiro L, Ruf S, Wolff M, Born J, Ngo HV. Auditory stimulation during sleep suppresses spike activity in benign epilepsy with centrotemporal spikes. Cell Rep Med 2021;2(11):100432. PMID 34841286
91: Kramer MA, Ostrowski LM, Song DY, et al. Scalp recorded spike ripples predict seizure risk in childhood epilepsy better than spikes. Brain 2019;142(5):1296-309. PMID 30907404
92: Kramer U, Nevo Y, Neufeld MY, Fatal A, Leitner Y, Harel S. Epidemiology of epilepsy in childhood: a cohort of 440 consecutive patients. Pediatr Neurol 1998;18(1):46-50. PMID 9492091
93: Kramer U, Zelnik N, Lerman-Sagie T, Shahar E. Benign childhood epilepsy with centrotemporal spikes: clinical characteristics and identification of patients at risk of multiple seizures. J Child Neurol 2002;17(1):17-9. PMID 11913563
94: Larsson K, Eeg-Olofsson O. A population based study of epilepsy in children from a Swedish county. Eur J Paediatr Neurol 2006;10(3):107-13. PMID 16638642
95: Leal A, Calado E, Vieira JP, et al. Anatomical and physiological basis of continuous spike-wave of sleep syndrome after early thalamic lesions. Epilepsy Behav 2018;78:243-55. PMID 29133062
96: Lee EH, You SJ. Factors associated with electroencephalographic and clinical remission of benign childhood epilepsy with centrotemporal spikes. Brain Dev 2019;41(2):158-62. PMID 30205923
97: Lemke JR, Lal D, Reinthaler EM, et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet 2013;45(9):1067-72. PMID 23933819
98: Lerman P, Kivity S. Benign focal epilepsy of childhood. A follow-up study of 100 recovered patients. Arch Neurol 1975;32:261-4. PMID 804895
99: Lerman P, Kivity S. The benign partial nonrolandic epilepsies. J Clin Neurophysiol 1991;8:275-87. PMID 1918333
100: Lerman P, Lerman-Sagie T. Sulthiame revisited. J Child Neurol 1995;10:241-2. PMID 7642898
101: Li Q, Westover MB, Zhang R, Chu CJ. Computational evidence for a competitive thalamocortical model of spikes and spindle activity in rolandic epilepsy. Front Comput Neurosci 2021a;15:680549. PMID 34220477
102: Li Y, Feng J, Zhang T, et al. Brain metabolic characteristics distinguishing typical and atypical benign epilepsy with centro-temporal spikes. Eur Radiol 2021b;31(12):9335-45. PMID 34050803
103: Li Y, Sun Y, Niu K, et al. The relationship between neuromagnetic activity and cognitive function in benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2020a;112:107363. PMID 32858366
104: Li Z, Zhang J, Wang F, et al. Surface-based morphometry study of the brain in benign childhood epilepsy with centrotemporal spikes. Ann Transl Med 2020b;8(18):1150. PMID 33240999
105: Lima EM, Rzezak P, Guimaraes CA, et al. The executive profile of children with benign epilepsy of childhood with centrotemporal spikes and temporal lobe epilepsy. Epilepsy Behav 2017;72:173-7. PMID 28622557
106: Lima EM, Rzezak P, Montenegro MA, Guerreiro MM, Valente KDR. Social cognition in childhood epilepsy with centrotemporal spikes. Seizure 2020;78:102-8. PMID 32335335
107: Lin JJ, Riley JD, Hsu DA, et al. Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes. Epilepsia 2012;53(4):677-85. PMID 22360313
108: Lischka A, Graf M. Benign rolandic epilepsy of childhood: topographic EEG analysis. Epilepsy Res Suppl 1992;6:53-8. PMID 1418492
109: Liu C, Song M, Wang J. Nightly oral administration of topiramate for benign childhood epilepsy with centrotemporal spikes. Childs Nerv Syst 2016;32(5):839-43. PMID 26984807
110: Liu MJ, Su XJ, Shi XY, et al. Clinical features of benign epilepsy of childhood with centrotemporal spikes in Chinese children. Medicine (Baltimore) 2017;96(4):e5623. PMID 28121917
111: Liu Z, Ye X, Zhang J, Wu B, Dong S, Gao P. Biallelic ADGRV1 variants are associated with Rolandic epilepsy. Neurol Sci 2022;43(2):1365-74. PMID 34160719
112: Loiseau P, Beaussart M. The seizures of benign childhood epilepsy with rolandic paroxysmal discharges. Epilepsia 1972;14:381-9. PMID 4521094
113: Loiseau P, Duche B, Cordova S, Dartigues JF, Cohadon S. Prognosis of benign childhood epilepsy with centrotemporal spikes. A follow-up study of 168 patients. Epilepsia 1988;29:229-35. PMID 3371279
114: Lombroso CT. Sylvian seizures and midtemporal spike foci in children. Arch Neurol 1967;17:52-9. PMID 6026172
115: Lu L, Xiong W, Zhang Y, Xiao Y, Zhou D. Propofol-induced refractory status epilepticus at remission age in benign epilepsy with centrotemporal spikes: a case report and literature review. Medicine (Baltimore) 2019;98(27):e16257. PMID 31277145
116: Luo T, Wang J, Zhou Y, et al. EMD-WOG-2DCNN based EEG signal processing for Rolandic seizure classification. Comput Methods Biomech Biomed Engin 2022;1-11. PMID 35044293
117: Matos M, Bara T, Clark S, Zeigelboim BS, Marques JM, Liberalesso PBN. Benign rolandic epilepsy of childhood and central auditory processing disorder: a noncasual neurophysiological association. Epilepsy Behav 2018;89:55-8. PMID 30384100
118: Metz-Lutz MN, Filippini M. Neuropsychological findings in Rolandic epilepsy and Landau-Kleffner syndrome. Epilepsia 2006;47(Suppl 2):71-5. PMID 17105467
119: Minami T, Gondo K, Yamamoto T, Yanai S, Tasaki K, Ueda K. Magnetoencephalographic analysis of rolandic discharges in benign childhood epilepsy. Ann Neurol 1996;39(3):326-34. PMID 8602751
120: Misiunas AVM, Meskauskas T, Samaitiene R. Algorithm for automatic EEG classification according to the epilepsy type: Benign focal childhood epilepsy and structural focal epilepsy. Biomed Sig Proc Control 2019;48:118-27.
121: Mitsudome A, Ohfu M, Yasumoto S, et al. The effectiveness of clonazepam on the rolandic discharges. Brain Dev 1997a;19(4):274-8. PMID 9187478
122: Mitsudome A, Ohu M, Yasumoto S, Ogawa A. Rhythmic slow activity in benign childhood epilepsy with centrotemporal spikes. Clin Electroencephalogr 1997b;28(1):44-8. PMID 9013050
123: Miziara CS, de Manreza ML, Mansur L, et al. Impact of benign childhood epilepsy with centrotemporal spikes (BECTS) on school performance. Seizure 2012;21(2):87-91. PMID 22221922
124: Monjauze C, Tuller L, Hommet C, Barthez MA, Khomsi A. Language in benign childhood epilepsy with centro-temporal spikes abbreviated form: Rolandic epilepsy and language. Brain Lang 2005;92(3):300-8. PMID 15721962
125: Nayrac P, Beaussart M. Les pointes-ondes prerolandiques: expression EEG tres particuliere. Etude electroclinique de 21 cas. Rev Neurol (Paris) 1958;99:201-6. PMID 13624406
126: Neng X, Xiao M, Yuanlu C, Qinyan L, Li S, Zhanyi S. Novel variant in CHRNA4 with benign childhood epilepsy with centrotemporal spikes and contribution to precise medicine. Mol Genet Genomic Med 2020;8(7):e1264. PMID 32342646
127: Northcott E, Connolly AM, Berroya A, et al. The neuropsychological and language profile of children with benign rolandic epilepsy. Epilepsia 2005;46(6):924-30. PMID 15946332
128: Oates S, Absoud M, Goyal S, et al. ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder. Clin Genet 2021;100(4):412-29. PMID 34216016
129: Oliveira EP, Neri ML, Capelatto LL, Guimarães CA, Guerreiro MM. Rolandic epilepsy and dyslexia. Arq Neuropsiquiatr 2014;72(11):826-31. PMID 25410447
130: Operto FF, Pastorino GMG, Mazza R, et al. Cognitive profile in BECTS treated with levetiracetam: a 2-year follow-up. Epilepsy Behav 2019;97:187-91. PMID 31252277
131: Otsubo H, Chitoku S, Ochi A, et al. Malignant rolandic-sylvian epilepsy in children: diagnosis, treatment, and outcomes. Neurology 2001;57(4):590-6. PMID 11524465
132: Ozgen Y, Gungor M, Kutlu M, Kara B. Clinical and electrophysiological predictors of behavioral disorders in patients with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2021;121(Pt A):108037. PMID 34058495
133: Pan A, Gupta A, Wyllie, E, Luders H, Bingaman W. Benign focal epileptiform discharges of childhood and hippocampal sclerosis. Epilepsia 2004;45(3):284-8. PMID 15009232
134: Panayiotopoulos CP. Benign childhood partial epilepsies: benign childhood seizure susceptibility syndrome. J Neurol Neurosurg Psychiatry 1993;56:2-5. PMID 8429319
135: Panayiotopoulos CP. Benign Childhood Partial Seizures and Related Epileptic Syndromes. London: John Libbey & Co Ltd, 1999.
136: Panayiotopoulos CP, Michael M, Sanders S, Valeta T, Koutroumanidis M. Benign childhood focal epilepsies: assessment of established and newly recognized syndromes. Brain 2008;131(Pt 9):2264-86. PMID 18718967
137: Parisi P, Paolino MC, Raucci U, Ferretti A, Villa MP, Trenite DK. “Atypical forms" of benign epilepsy with centrotemporal spikes (BECTS): how to diagnose and guide these children. A practical/scientific approach. Epilepsy Behav 2017;75:165-9.** PMID 28866336
138: Park YK, Eun SH, Eun BL, Byeon JH. Factors predicting poor response to initial therapy in benign childhood epilepsy with centrotemporal spikes (BCECTS). J Epilepsy Res 2015;5(2):70-4. PMID 26819938
139: Perlstein MA, Gibbs EL, Gibbs FA. The electroencephalogram in infantile cerebral palsy. In: Lennox WG, Merritt HH, Bamford TE, editors. Epilepsy (proceedings of the association for research in nervous and mental disease, research publications, vol 26). Baltimore: Williams & Wilkins, 1947:377-84.
140: Porat Rein A, Kramer U, Hausman Kedem M, Fattal-Valevski A, Mitelpunkt A. Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes. Brain Dev 2020;S0387-7604(20)30242-4.** PMID 32912653
141: Prats JM, Garaizar C, Garcia-Nieto ML, Madoz P. Antiepileptic drugs and atypical evolution of idiopathic partial epilepsy. Pediatr Neurol 1998;18(5):402-6. PMID 9650679
142: Ramos IDSS. Coelho CVG, Ribeiro F, Lopes AF. Executive functioning in children with self-limited epilepsy with centrotemporal spikes: a systematic review and meta-analysis. Child Neuropsychol 2022; 28(1):30-60. PMID 34251988
143: Ramos LLP, Monteiro FP, Sampaio LPB, et al. Heterozygous loss of function of NR4A2 is associated with intellectual deficiency, rolandic epilepsy, and language impairment. Clin Case Rep 2019;7(8):1582-4. PMID 31428396
144: Rating D, Wolf C, Bast T. Sulthiame as monotherapy in children with benign childhood epilepsy with centrotemporal spikes: a 6-month randomized, double-blind, placebo-controlled study. Sulthiame Study Group. Epilepsia 2000;41(10):1284-8. PMID 11051123
145: Reinthaler EM, Dejanovic B, Lal D, et al. Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes. Ann Neurol 2015;77(6):972-86. PMID 25726841
146: Robertson R, Langill L, Wong PK, Ho HH. Rett syndrome: EEG presentation. Electroencephalogr Clin Neurophysiol 1988;70:388-95. PMID 2460312
147: Ross EE, Stoyell SM, Kramer MA, Berg AT, Chu CJ. The natural history of seizures and neuropsychiatric symptoms in childhood epilepsy with centrotemporal spikes (CECTS). Epilepsy Behav 2020;103(Pt A):106437.** PMID 31645314
148: Sanlidag B, Koken OY, Temel EU, Arhan E, Aydin K, Serdaroglu A. Benign epilepsy with centrotemporal spikes: Is there a thalamocortical network dysfunction present? Seizure 2020;79:44-8. PMID 32416566
149: Santanelli P, Bureau M, Magaudda A, Gobbi O, Roger J. Benign partial epilepsy with centrotemporal (or rolandic) spikes and brain lesion. Epilepsia 1989;30(2):182-8. PMID 2494043
150: Sathyanarayana A, El Atrache R, Jackson M, et al. Nonlinear analysis of visually normal eegs to differentiate benign childhood epilepsy with centrotemporal spikes (BECTS). Sci Rep 2020;10(1):8419. PMID 32439999
151: Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58(4):512-21. PMID 28276062
152: Sheth RD, Gutierrez AR, Riggs JE. Rolandic epilepsy and cortical dysplasia: MRI correlation of epileptiform discharges. Pediatr Neurol 1997;17(2):177-9. PMID 9367303
153: Shevell MI, Rosenblatt B, Watters GV, O’Gorman AM, Montes JL. “Pseudo-BECRS”: intracranial focal lesions suggestive of a primary partial epilepsy syndrome. Pediatr Neurol 1996;14(1):31-5. PMID 8652012
154: Shi XY, Wang G, Li T, et al. Identification of susceptibility variants to benign childhood epilepsy with centro-temporal spikes (BECTS) in Chinese Han population. EBioMedicine 2020;57:102840. PMID 32580138
155: Shields WD, Saslow E. Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children. Neurology 1983;33(11):1487-9. PMID 6415512
156: Siripornpanich V, Visudtibhan A, Kotchabhakdi N, Chutabhakdikul N. Delayed cortical maturation at the centrotemporal brain regions in patients with benign childhood epilepsy with centrotemporal spikes (SLECTS). Epilepsy Res 2019;154:124-31. PMID 31129368
157: Smith AB, Bajomo O, Pal DK. A meta-analysis of literacy and language in children with rolandic epilepsy. Dev Med Child Neurol 2015;57(11):1019-26. PMID 26219529
158: Smith SDW, Smith AB, Richardson MP, Pal DK. Neurodevelopmental origins of self-limiting rolandic epilepsy: systematic review of MR imaging studies. Epilepsia Open 2021;6(2):310-22. PMID 34033258
159: Sreenivasan A, Krishna R, Nair PP, Kasinathan A, Alexander A. Evaluation of auditory spectral resolution abilities in children with benign epilepsy with centrotemporal spikes using spectral temporally modulated ripple test. Epilepsy Behav 2021;114(Pt A):107620. PMID 33268014
160: Stephen J, Weir CJ, Chin RF. Temporal trends in incidence of Rolandic epilepsy, prevalence of comorbidities and prescribing trends: birth cohort study. Arch Dis Child 2020;105(6):569-74. PMID 31937568
161: Suo GH, Zheng YQ, Wu YJ, Tang JH. Effects of levetiracetam and oxcarbazepine monotherapy on intellectual and cognitive development in children with benign epilepsy with centrotemporal spikes. Acta Neurol Belg 2021;121(5):1265-73. PMID 33590471
162: Tacke M, Borggraefe I, Gerstl L, et al. Corrigendum to "EEG changes in rolandic epilepsy under treatment with levetiracetam and sulthiame" [Eur J Paediatr Neurol 21 (Suppl. 1) (June 2017) e97]. Eur J Paediatr Neurol 2017;21(6):e1. PMID 28797736
163: Tang H, Wang Y, Hua Y, Wang J, Jing M, Hu X. Analysis of serial electroencephalographic predictors of seizure recurrence in Rolandic epilepsy. Childs Nerv Syst 2019;35(9):1579-83. PMID 31267183
164: Tang SS, Clarke T, Owens J, Pal DK. Sleep behavior disturbances in rolandic epilepsy. J Child Neurol 2011;26(2):239-43. PMID 21098331
165: Teixeira JM, Santos ME, Oom P. Oral language in children with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2020;111:107328. PMID 33027869
166: Tekgul H, Kanmaz S, Serin HM, Yilmaz S. Spike wave characteristics and temporal spike evolution on serial EEG in childhood epilepsy with centrotemporal spikes. Seizure 2021;87:75-80. PMID 33725524
167: Thorn EL, Ostrowski LM, Chinappen DM, et al. Persistent abnormalities in Rolandic thalamocortical white matter circuits in childhood epilepsy with centrotemporal spikes. Epilepsia 2020;61(11):2500-8. PMID 32944938
168: Tornhage M, Sandberg EN, Lundberg S. Oromotor, word retrieval, and dichotic listening performance in young adults with previous Rolandic epilepsy. Eur J Paediatr Neurol 2020;25:139-44. PMID 31866100
169: Tristano I, Nicita F, Garone G, et al. Could Rolandic spikes be a prognostic factor of the neurocognitive outcome of children with BECTS? Epilepsy Behav 2018;86:157-62. PMID 30031676
170: Tsai MH, Vears DF, Turner SJ, et al. Clinical genetic study of the epilepsy-aphasia spectrum. Epilepsia 2013;54(2):280-7. PMID 23294109
171: Tsai ML, Hung KL. Topographic mapping and clinical analysis of BCECS. Brain Dev 1998;20(1):27-32. PMID 9533557
172: Vadlamudi L, Kjeldsen M, Corey L, et al. Analyzing the etiology of benign rolandic epilepsy: a multicenter twin collaboration. Epilepsia 2006;47(3):550-5. PMID 16529620
173: Van Bogaert P, Wikler D, Damhaut P, Szliwowski HB, Goldman S. Cerebral glucose metabolism and centrotemporal spikes. Epilepsy Res 1998;29(2):123-7. PMID 9477144
174: van Klink NE, van 't Klooster MA, Leijten FS, Jacobs J, Braun KP, Zijlmans M. Ripples on rolandic spikes: a marker of epilepsy severity. Epilepsia 2016;57(7):1179-89. PMID 27270830
175: Varesio C, Zanaboni MP, Salmin EC, et al. Childhood epilepsy with centrotemporal spikes: clinical and neuropsychological outcomes 5 years after remission. Diagnostics (Basel) 2020;10(11):931. PMID 33182826
176: Vega YH, Smith A, Cockerill H, et al. Risk factors for reading disability in families with rolandic epilepsy. Epilepsy Behav 2015;53:174-9. PMID 26580214
177: Verrotti A, Casciato S, Spalice A, et al. Coexistence of childhood absence epilepsy and benign epilepsy with centrotemporal spikes: a case series. Eur J Paediatr Neurol 2017;21(3):570-5. PMID 28238620
178: Vinayan KP, Biji V, Thomas SV. Educational problems with underlying neuropsychological impairment are common in children with Benign Epilepsy of Childhood with Centrotemporal Spikes (BECTS). Seizure 2005;14(3):207-12. PMID 15797356
179: Wang F, Yin Y, Yang Y, et al. Connectome-based prediction of brain age in Rolandic epilepsy: a protocol for a multicenter cross-sectional study. Ann Transl Med 2021a;9(6):511. PMID 33850908
180: Wang P, Li Y, Sun Y, et al. Altered functional connectivity in newly diagnosed benign epilepsy with unilateral or bilateral centrotemporal spikes: a multi-frequency MEG study. Epilepsy Behav 2021b;124:108276. PMID 34547687
181: Watanabe K. Benign partial epilepsies. In: Wallace SJ, Farrell K, editors. Epilepsy in children. 2nd ed. London: Arnold, 2004:199-220.
182: Watemberg N, Afunevitz S, Ganelin-Cohen E, Mahajnah M. Clinical features at the time of diagnosis of benign epilepsy with centrotemporal spikes do not predict subsequent seizures. Pediatr Neurol 2018;88:36-9. PMID 30337131
183: Weglage J, Demsky A, Pietsch M, Kurlemann G. Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures. Dev Med Child Neurol 1997;39(10):646-51. PMID 9352724
184: Wickens S, Bowden SC, D'Souza W. Cognitive functioning in children with self-limited epilepsy with centrotemporal spikes: a systematic review and meta-analysis. Epilepsia 2017;58(10):1673-85.** PMID 28801973
185: Wirrell EC, Camfield PR, Gordon KE, Dooley JM, Camfield CS. Benign rolandic epilepsy: atypical features are very common. J Child Neurol 1995;10(6):455-8. PMID 8576555
186: Wirrell EC, Hamiwka LD. Do children with benign rolandic epilepsy have a higher prevalence of migraine than those with other partial epilepsies or nonepilepsy controls. Epilepsia 2006;47(10):1674-81. PMID 17054690
187: Wu L, Yang X, Wang X, Yu S, Yang B. The attention networks in benign epilepsy with centrotemporal spikes: a long-term follow-up study. J Clin Neurosci 2021a;88:22-7. PMID 33992188
188: Wu L, Yang X, Zhang K, Wang X, Yang B. Impairment of eye emotion discrimination in benign childhood epilepsy with centrotemporal spikes: a neuropsychological study. Brain Behav 2021b;11(6):e02154. PMID 33942564
189: Xiao F, An D, Deng H, Chen S, Ren J, Zhou D. Evaluation of levetiracetam and valproic acid as low-dose monotherapies for children with typical benign childhood epilepsy with centrotemporal spikes (BECTS). Seizure 2014;23(9):756-61. PMID 24998415
190: Xu Q, Hu Z, Yang F, et al. Resting state signal latency assesses the propagation of intrinsic activations and estimates anti-epileptic effect of levetiracetam in Rolandic epilepsy. Brain Res Bull 2020;162:125-31. PMID 32535220
191: Xu Z, Wang T, Cao J, Bao Z, Jiang T, Gao F. BECT spike detection based on novel EEG sequence features and LSTM algorithms. IEEE Trans Neural Syst Rehabil Eng 2021;29:1734-43. PMID 34428145
192: You SJ, Kim DS, Ko TS. Benign childhood epilepsy with centro-temporal spikes (BCECTS): early onset of seizures is associated with poorer response to initial treatment. Epileptic Disord 2006;8(4):285-8. PMID 17150442
193: Zhang Q, He Y, Qu T, et al. Delayed brain development of Rolandic epilepsy profiled by deep learning-based neuroanatomic imaging. Eur Radiol 2021;31(12):9628-37. PMID 34018056
194: Zhang XW, Dai RP, Cheng GW, Zhang WH, Long Q. Altered amplitude of low-frequency fluctuations and default mode network connectivity in high myopia: a resting-state fMRI study. Int J Ophthalmol 2020;13(10):1629-36. PMID 33078115
195: Zhao X, Chi Z, Chi L, Shang W, Liu X. Clinical and EEG characteristics of benign rolandic epilepsy in Chinese patients. Brain Dev 2007;29(1):13-8. PMID 16806777

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Self-limited epilepsy with centrotemporal spikes

Associated Disorders

Idiopathic generalized seizures

Differential Diagnosis

cerebral palsy
Rett syndrome
structural focal epilepsies
mesial temporal lobe epilepsy
static brain lesions
- cerebral tumors
- focal cortical dysplasia
- malignant rolandic-sylvian epilepsy
- neuronal migration disorders
- gliotic scars
- other self-limited focal epilepsies of childhood

Also Relevant

Benign infantile seizures
Epilepsy
Epilepsy with myoclonic-atonic seizures
Landau-Kleffner syndrome
Lennox-Gastaut syndrome
- Panayiotopoulos syndrome
- Parasomnias
- Sleep and epilepsy

Clinical Categories

Epilepsy & Seizures

Self-limited epilepsy with centrotemporal spikes

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Clinical features

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Antiseizure medication treatment

Nonpharmacological treatment

Outcomes

Special considerations

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Congenital cytomegalovirus

Seizures of the posterior neocortex

Infantile epileptic spasms syndrome

Childhood absence epilepsy

Sudden unexpected death in epilepsy

Neocortical temporal lobe seizures

Pyridoxine/P5P-dependent developmental epileptic encephalopathy

Frontal lobe seizures

This is an article preview.
Start a Free Account
to access the full version.