Benign childhood epilepsy with centrotemporal spikes (BCECTS) is among the most frequent benign focal epilepsies in childhood and accounts for about 15%–25% of all epileptic syndromes in children with ages between 4 and 12 years.¹ The annual incidence ranges between 7.1 and 21 per 100,000 in children under the age of 15 years² with a slight male predominance.³ Absence of neurological and intellectual deficits are part of the definition, even though BCECTS has also been reported in patients with neuroradiologically documented cerebral lesions.^4,5 Genetic factors play an important etiological role, as corroborated by the higher incidence of positive family history for epilepsy and focal electroencephalographic (EEG) abnormalities in BCECTS patients.⁶ Linkage to chromosome 15q14 was pointed out,⁷ but not confirmed in several studies.⁸

Age at onset ranges between 4 and 10 years in 90% of patients, with a peak around 7 years. Seizures occur during sleep in 80%–90% of patients, and only while awake in less than 10%. Seizure frequency is usually low with 10% of patients experiencing one seizure only.¹ Duration of seizures commonly ranges from 30 seconds up to no more than 2–3 minutes. Major clinical findings include: (i) orofacial motor signs, specially tonic or clonic contractions of one side of the face with a predilection for the labial commissure (contralateral to centrotemporal spikes); (ii) speech arrest; (iii) sialorrhea, a characteristic ictal symptom which may not be related to increased salivation, swallowing disturbance, or both; (iv) somatosensory symptoms, represented by unilateral numbness or paresthesias of the tongue, lips, gums, and inner cheek. Less-frequent ictal manifestations include: (i) generalized seizures which are not infrequently observed in younger children and probably related to rapid generalization of focal seizures and (ii) postictal paresis.⁹

The benign character of Rolandic spikes was recognized in the 1950s.^10,11 Several long-term follow-up studies confirmed the good prognosis,^12,13,14,15 and over 90% of cases will achieve remission by age 12 years.¹⁶ The prognosis is favorable even for patients whose seizures are difficult to control, and seizures almost always remit spontaneously in adolescence. No differences in seizure frequency, seizure relapse rate, duration of active period of epilepsy, and social adjustments have been found between BCECTS patients receiving an antiepileptic drug (AED) and untreated patients.¹⁷ The only predictor of short-term prognosis is the age at BETCS onset: the earlier the onset of seizures, the longer the active period. The occurrence of GTCS seizures after recovery from BCECTS is a rare event, involving approximately 2% of subjects, similar to the incidence in partial seizures.¹⁸

EEG PATTERNS

The cornerstone of BCECTS diagnosis is the characteristic interictal EEG pattern. Background EEG activity is normal both during wakefulness and sleep. Interictal epileptic discharges and location of spikes include typical sharp/spike-waves located in centrotemporal or Rolandic areas (CTSW). CTSW are broad, diphasic, high-voltage (100–300 microvolts) sharps, with a horizontal dipole, and are often followed by a slow wave. Spikes may be isolated or in clusters,¹⁸ and focal rhythmic slow activity is occasionally observed in the same region as the spikes.¹⁹ The spikes may occur in one or both hemispheres. Bilateral synchronous discharges or independent CTSW appear in wakefulness or sleep in about one-third of cases²⁰ and the characteristic dipolar pattern in the EEG has been emphasized.²¹ Enhancement of discharges is observed in drowsiness and in all stages of sleep. In about one-third of children, spikes appear only in sleep.²² Spikes in other areas, multifocal paroxysms, and spike-wave discharges at the onset or during evolution may also appear.²³ In some cases, multifocal paroxysms are especially evident during sleep. Generalized spike-wave discharges are rarely seen in the waking state, but may be frequent during drowsiness and sleep.^24,25 Ictal EEG patterns are generally characterized by a sequence of rhythmic spikes remaining monomorphous throughout the sequence.

Atypical Features in Patients with BCECTS

Children with BCECTS are classically considered free of neuropsychological impairments.²⁶ However, learning, language, and behavioural disabilities are present in many affected patients,²⁷ but are less frequent compared to other forms of childhood epilepsy. We have reviewed a large list of transient neuropsychological impairments in children with atypical features of BCECTS.²⁸ In a study investigating the influence of cognition on quality of life of 30 children with BCECTS, parental emotional impact was the major independent predictor of quality of life.²⁹ However, even when children with BCECTS show some learning difficulties, the intellectual abilities or behavior disorders did not differ from healthy children,³⁰ and a vast majority of the patients attend normal schools. In adolescents and young adults in complete remission from BCECTS there were no significant differences with controls in cognitive functions. It has recently been noted that all attentional networks (alerting, orienting, and executive attention networks) are impaired in children with active centrotemporal spikes and that these impairments resolve upon EEG remission.³¹ By contrast, qualitative analysis suggested a different organizational pattern for cerebral language.³²

These transient sectorial cognitive impairments tend to occur in the active phase of the disease, and appear more correlated to the ongoing epileptiform activity in the awake state and, in particular, during NON-REM sleep than to seizure frequency.^33,34,35 More frequently, visual perception, short-term memory, memory, phonologic awareness, reading, spatial perception, including spatial orientation, numeracy and/or spelling abilities are significantly delayed.^36,37,38

Six distinct interictal EEG patterns are hallmarks of BCECTS patients who, after complete seizure remission and normalization of the EEG, evidenced serious cognitive difficulties and impaired quality of life at home and at school.³⁹

In a study with combination of EEG, magnetoencephalography and MRI, BCECTS children with lower language test scores had left perisylvian spikes, while children with right perisylvian location performed within normal ranges in all parts of the tests.⁴⁰

It is important to employ appropriate neuropsychological tests patients in BCECTS. In a study of 21 children with BCECTS compared to controls, tests measuring phonemic fluency, verbal reelaboration of semantic knowledge, and lexical comprehension showed mild language defects that correlated with a high spike frequency in wakefulness, multifocal location, and temporal prominence of EEG spike-wave discharges.⁴¹

A significantly higher percentage of learning and behavioral disabilities are reported in BCECTS patients with atypical features. No patient developed status epilepticus, Landau Kleffner syndrome, or CSWSS syndrome.⁴²

Gobbi et al⁴³ suggested that these conditions be termed BCECTS “plus” disorders to differentiate them from the other Rolandic epilepsy-related disorders such as ABPE/pseudo Lennox syndrome, CSWS, acquired epileptic frontal syndrome, LKS ± CSWS, and the early development dysphasia ± CSWS (or LKS variant) (Table 25–1). A differentiation between “malignant” and “nonmalignant” forms of atypical presentations of BCECTS was also proposed.⁴⁴

Atypical BCECTS

The term “atypical BCECTS” is used to describe a subset of patients with severe epileptic manifestations and marked language, and cognitive or behavioral impairments. Aicardi and Chevrie⁴⁵ first described this condition in seven children with BCECTS during periods of new types of seizures, mainly atonic and myoclonic, associated with continuous spike-wave discharges in slow wave sleep (CSWS/ESES [electrical status epilepticus during sleep]), and transient deterioration in school performance. They used the term “atypical benign partial epilepsy of childhood” (ABPE) and commented that the majority had been previously diagnosed as Lennox-Gastaut syndrome. In fact, in the German literature this condition was named “Pseudo Lennox Syndrome.”⁴⁶ As BCECTS may occur in patients with brain lesions, ABPE (or Pseudo Lenox Syndrome) may be both idiopathic and symptomatic in origin.

ABPE can be a particularly severe with respect to its cognitive consequences. In a recent prospective study of 44 children that included 28 with typical BCECTS, and 16 with ABPE, patients from the latter group had significantly lower full scale and verbal intelligence quotient scores. Abnormalities were also noted in performance tasks.

Neuropsychological impairments may precede the onset of the disorder, and persist consistently during the clinical course. Long-term follow-up reveals persistent verbal deficits in all ABPE patients after remission, and the longer the duration of ESES pattern the more severe are permanent cognitive impairments.⁴⁷ However, in the experience of one of us (NF), seizures remitted in all 16 patients with ABPE and the EEG normalized; none resented significant neurocognitive sequelae.⁴⁸

CSWS/ESES has also been reported in some patients with the so-called “status of BCECTS.” Status of BCECTS, or status epilepticus of benign partial epilepsy in children, which may last days or weeks, has been described by Fejerman and Di Blasi in 1987, and Colamaria et al in 1991.^49,50 Clinical semiology consists of focal motor seizures such as anarthria, dysarthria, sialorrhea, drooling, oromotor dyspraxia, swallowing difficulties, hemifacial contraction, and atonic head nods. Focal atonic events (epileptic negative myoclonus) may be so frequent to cause limb difficulties. The ictal EEG is characterized by continuous bilateral or diffuse spike discharges that predominate in the Rolandic regions, may be synchronous with hemifacial twitching and inhibited by voluntary mouth and tongue movements. Interictal awake EEG shows bilateral sharp- and sharp-slow wave complexes with higher amplitude in the Rolandic area, which increases during sleep and bilateral synchronization. Continuous spike-waves during slow sleep may also occur in some patients (see Section “Atypical BCECTS“).

In a minority of patients, BCECTS may evolve into Landau-Kleffner syndrome (LKS) and the continuous spike-and-wave during slow sleep syndrome (CSWSS), and vice versa.^{48,51,52,53,54} It remains to be defined whether these conditions—ABPE (or pseudo lenox syndrome), LKS (and LKS variant), CSWSS (including the acquired epileptic frontal syndrome)—are independent syndromes or syndromes related to BCECTS as part of a continuum. In this context, the atypical evolution in a minority of patients with BCECTS may possibly be considered as “system epilepsy.”⁵⁵

DIAGNOSTIC CRITERIA

Criteria for diagnosis include typical Rolandic seizures especially during sleep, normal psychomotor and mental development, normal neurological examination, and the characteristic awake and sleep EEG patterns. Therefore, awake and sleep EEG recording is mandatory for diagnosis. A comprehensive neuropsychological assessment should be performed at the onset of the disorder. In fact, any sign of neuropsychological impairments or of learning disorders may suggest atypical features of BCECTS or atypical BCECTS.

Structural neuroimaging studies, when the clinical and EEG features are typical should be avoided.⁵⁶ Hippocampal asymmetries and white matter abnormalities in MRI have been reported in 33% of 18 children with BCECTS, although their etiology was considered unclear.⁵⁷ Cases with electroclinical phenotypes of BCECTS associated with brain malformations such as cortical dysplasia^17,58 or heterotopia^51,53 and with nonevolutive clastic brain lesions⁴ have also been described. Therefore, it is reasonable to suggest an MRI if there is suspicion of associated abnormalities.

Karyotype analysis is needed to exclude chromosomal disorders which may have an EEG pattern similar to BCECTS including fragile X (FRAXA) syndrome, deletion of chromosome 7,⁵⁹ inv-dup15 (GG, personal observation), and Klinefelter syndrome.⁶⁰