**Abstract**

Childhood epilepsy with centrotemporal spikes, had been previously considered as benign childhood epilepsy. According to the new classification proposed by Sheffer I. and colleagues the term "benign" has been changed to "selflimited". Many studies reported that BECTS may cause transient or long lasting cognitive and behavioral disturbances. Rolandic epilepsy is the most frequent among the childhood focal epilepsy and may account for about 15–25% of all epileptic syndromes diagnosed between the ages of 5 to 15 years. The incidence range changes between 7.1–21 per 100000 in population younger than 15 years with male predominance. The age of onset in 90% of cases between 1 and 10 years with peak around 6–7 years. Seizures mainly occur during a night sleep, whereas the probability of awake seizures are less than 10%. The characteristic clinical features are: (1) focal motor seizure with unilateral orofacial tonic or clonic contractions; (2) speech arrest; (3) hypersalivation; (4) sensory symptoms represented by unilateral numbness or paresthesia of tongue, lips, gum and inner part of the check; (5) unilateral clonic jerk in leg and arm with postictal paresis; (6) generalized seizures. The EEG picture is distinctive in Rolandic epilepsy. The background activity is almost always preserved in awake state and during a sleep. The typical interictal EEG pattern is high voltage, diphasic spikes or sharp waves frequently with slow activity on central-midtemporal region. The centrotemporal spikes or rolandic spikes come from the lower rolandic region created a horizontal dipole with maximal electronegativity in the centrotemporal region and electropositivity in the frontal region usually seen unilateral or bilateral. In most cases children with RE have a good prognosis regarding both seizures and neurodevelopment. The remission of seizures usually occurs before the age of 18 years. The cognitive and behavior problem may happen in active period of disease which are reversable in most of patients.

**Keywords:** rolandic epilepsy, EEG, BECTS, epilepsy, atypical rolandic epilepsy, centrotemporal spikes, seizures, cognitive outcome

## **1. Introduction**

Self-limited epilepsy with centrotemporal spikes (SECTS), well-known as Rolandic epilepsy is the most frequent among the childhood focal epilepsies and may account for about 15–25% of all epileptic syndromes diagnosed between the ages of 5 to 15 years [1]. It is termed 'rolandic' epilepsy because the focal seizures are originated from the region around the lower part of the central gyrus of Rolando. The incidence range changes between 7.1–21 per 100000 in a population younger than 15 years with male predominance [2]. The age of onset in 90% of cases between 1 and 10 years with a peak around 6–7 years and recovery occurs before the age of 15–16 years [2–4].

Self-limited epilepsy with centrotemporal spikes is a syndrome of brief hemifacial motor seizures, frequently having associated somatosensory symptoms, usually without impairment of consciousness which tend to evolve into GTCS [3–6]. Seizures are often related to sleep [7]. Genetic predisposition is frequent, and there is male predominance [3, 5, 8, 9]. An interictal EEG has normal background activity with biphasic high-voltage centrotemporal spikes, often followed by slow waves that are activated by sleep and tend to spread or shift from side to side [10]. Neurological and mental status before the debut of epilepsy is normal. There are no specific abnormalities on brain MRI or CT. Many studies reported that RE may cause transient or long-lasting cognitive and behavioral disturbances [4, 5, 11–40].

## **2. Terminology and classification**

Panayiotopoulos described a concept of benign childhood susceptibility syndrome (BCSSS) to unify RE, Panayiotopoulos syndrome (PS) and childhood occipital epilepsy of Gastaut (ICOE-G) outlined the common features, course of diseases, prognosis, and the possible genetic predisposition in this group of associated syndromes [5].

1989 ILAE classification recognized three "age-related and localization-related epilepsies and syndromes": (1) benign childhood epilepsy with centrotemporal spikes (BCECTS); (2) childhood epilepsy with occipital paroxysms; (3) primary reading epilepsy [10].

ILAE Commission on Classification and Terminology lists three childhood idiopathic focal epilepsy syndromes: (1) benign childhood epilepsy with centrotemporal spikes (BCECTS); (2) Panayiotopoulos syndrome, and (3) late-onset childhood occipital epilepsy (Gastaut type) [13].

Rolandic epilepsy had undergone significant terminological and classification changes. RE had been previously considered as benign childhood epilepsy. Frequently reported cognitive and language impairments and behavioral disturbances in children with RE led to the replacement of the terms "benign" and "idiopathic" by the "self-limited" in the new classification proposed by Sheffer I. and colleagues [41].

## **3. Etiology**

The role of genetic factors in RE has been presumed since the first high incidence of centrotemporal spikes in family members of patients with RE was reported in 1964 [42]. RE and related syndromes with atypical features do not follow a Mendelian inheritance mode [43]. The clinical and genetic studies have shown complex inheritance [43–51].

The genetics of CTS is not the same as the clinical genetics of RE [52]. Although CTS is the primary EEG characteristics of RE or ARE, they are also observed in healthy children [53] or the children with autistic spectrum disorders without seizures [54]. Only 10% of EEG trait carriers had seizures [55, 56]. An autosomal dominant mode of

#### *Rolandic Epilepsy: Self-Limited Epilepsy with Centrotemporal Spikes DOI: http://dx.doi.org/10.5772/intechopen.96148*

inheritance of CTS on EEG has been reported by several authors [42, 55, 56] but it is still debated [52]. The linkage of CTS to ELP4-PAX6 region on 11p13 and chromosome 15q13 [57], 16p12–11.2 [58], and 15q14 [59] have been identified.

Doose et al. investigated the broad spectrum clinical and EEG manifestation of 147 children with RE and their 1266 family members revealed a high incidence of febrile convulsion and afebrile GTCS in patients and their relatives suggested multifactorial inheritance. EEG recordings of probands and their siblings showed a high rate of generalized EEG traits [43].

A multicentral twin study of eighteen twin pairs (10 MZ, 8 DZ) based on a twin database done by Vadlamudi and colleagues demonstrated that the etiology of RE and its inheritance mode is much more complicated than considered before [44]. No twin pairs were concordant for RE. Only one monozygotic twin pair has shown centrotemporal spikes on EEG without seizures. Another intriguing finding from this twin data was that all twin pairs with atypical features RE, had a co-twin with seizures although discordant for RE, which emphasized that genetic factors may be more important in atypical cases of RE.


#### **Table 1.**

*Genetic mutations associated with RE/ARE spectrum.*

The genetic basis of RE/ARE is polygenic and complex, the interaction of environmental factors or other genes should be considered in etiology of RE spectrum epilepsy syndromes [60, 61]. A number of genes were found to follow the Mendelian inheritance and be associated with RE/ARE (**Table 1**).

Lemke et al., have identified GRIN2A mutations in 20% of patients with ARE associated with neurocognitive disturbances [66].

Although mutations in PRRT2, KCNQ2, KCNQ3, RBFOX1, and DEPDC5 genes with an autosomal dominant transmission reported in patients with RE spectrum epilepsy syndromes, they have not been confirmed by the studies based on large case series [70].

With the exception of GRIN2A and ELP4, many genes currently associated with RE/ARE, including KCNQ2, KCNQ3, CHRNA4, DEPDC5, RBFOX1/3, BDNF, and GABAA-R, were initially linked to other neurogenetic conditions, and later their phenotypes were expanded to RE/ARE.

### **4. Clinical features**

The main seizure type in RE according to the ILAE 2017 seizure classification is focal aware seizure consisting of motor-hemifacial tonic or clonic contractions, oro-pharyngo-laryngeal symptoms, sensory symptoms represented by unilateral numbness or paresthesia of tongue, lips, gum, and inner part of the check, and associated with speech arrest, hypersalivation, and focal to bilateral seizures [2–4, 41, 71]. Hemiconvulsions and bilateral tonic–clonic seizures are less frequently observed ictal features, mainly seen in younger children due to rapid distribution of focal onset seizures [2–4, 6]. Hemiconvulsions may be followed by post-ictal Todd's hemiparesis in 10% of cases [8, 72].

Seizures are brief, usually last from 30 sec to 2–3 minutes or longer if turn into bilateral tonic–clonic seizures [6, 18, 72]. Seizures mainly occur during night sleep or drowsiness, whereas the probability of awake seizures is less than 10% [73, 74]. Seizure frequency is low, most patients have less than 10 seizures, 10%–20% of patients have a single seizure [75]. Consciousness is completely preserved in around 60% of patients with RE [5].

*Focal motor seizures* in approximately one-third of cases manifest as unilateral oral-facial tonic or clonic contractions. These are brief (few seconds −1 min), a sudden burst of clonic contractions of the face, which may be entirely localized in the lower lip or spread to the ipsilateral upper and very rare to the lower extremities [1–5, 71, 76].

Tonic deviation of the mouth is frequently observed ictal motor manifestation [5]. *Oro-pharyngo-laryngeal symptoms* are mostly motor ictal phenomena with the involvement of the (epi-) glottis and pharynx (> 50%) produce guttural bizarre sounds, resembling gargling, grunting, wheezing [72]. These may be accompanied by contractions of the respiratory and abdominal muscles (vomiting like contractions) which appear in more than half of seizures [77]. They consist of unilateral sensory and motor manifestations inside the mouth, tongue, inner cheek, gums, teeth, and pharyngolaryngeal regions [3].

*Speech arrest* occurs in >40% of seizures with dys - or anarthria [3, 72]. The child usually is aware, with preserved receptive language, attempts to communicate with gestures, but unable to produce a single intelligible word [3, 5]. Speech arrest is considered more as a motor ictal manifestation associated with the loss of the power and coordination for the articulation of words [3]. There is no impairment of the cortical language mechanisms [4, 5].

*Focal non-motor seizures* commonly observed in RE.

*Rolandic Epilepsy: Self-Limited Epilepsy with Centrotemporal Spikes DOI: http://dx.doi.org/10.5772/intechopen.96148*

*Sensory symptoms* may manifest as unilateral numbness or paraesthesias like tingling, prickling, freezing and their variations in the parts (rarely involve the whole area) of oral-facial-pharyngeal area, usually tongue, inner cheek, gum, teeth, lips [3, 4, 6]. Sensory seizures often occur in combination with motor seizures and hypersalivation [3, 5, 72].

*Hypersalivation* is one of the most characteristic autonomic ictal symptoms of RE, occurs in one-third of cases [2–5, 71]. It is frequently associated with hemifacial motor symptoms. As well as the awareness is not disturbed in most of the cases, children usually are able to describe their sensations as sudden filling of the mouth with saliva and air, difficulty in pronouncing words, a lot of saliva flowing from the mouth [5].

Other autonomic ictal manifestations as *ictal emesis* and *ictal syncope* may observe rarely in RE. Although autonomic seizures are the cardinal symptom of Panayiotopoulos syndrome, they are reported in RE [74, 78–82]. The overlap of the clinical and EEG features of PS and RE has been widely investigated by several authors [5, 74, 79, 80]. The cases where two different types of childhood focal seizures presented at the same time or one form of epilepsy progressed to another have been thoroughly reported by different investigators [74, 79–85].

*Focal to bilateral tonic–clonic seizures* are a frequent seizure type present in one to two-thirds of children with RE. FBTCSs mostly appear during night sleep [86].

*Status epilepticus* is seen rarely and usually associated with an atypical course of the disease [87].

Focal motor SE occurs more often than generalized convulsive SE [3]. This state consists of unilateral or bilateral hemifacial contraction, subtle perioral myoclonus, speech arrest, dysarthria, excessive drooling, swallowing difficulties [88–93].

#### **5. EEG patterns**

#### **5.1 Interictal EEG**

The EEG picture is distinctive in Rolandic epilepsy. The background activity is almost always preserved in an awake state and during sleep [91]. The characteristic interictal EEG pattern- centrotemporal spikes (CTS) or rolandic spikes are regarded as the neurobiological markers of RE. CTS is high-amplitude (usually > than 150 mkV) biphasic spikes or sharp waves of ∼ 70–80 milliseconds duration frequently followed by a slow activity on the central-mid temporal region (C3/C4, T3/T4) [2–4]. More posterior localization of CTS is often observed in the youngest patients [94]. The spikes may occur isolated or in clusters, in one or both hemispheres [95, 96] (**Figure 1A** and **B**). A focal rhythmic slow activity over the centrotemporal region is occasionally observed [2]. The most typical finding of the rolandic spikes is their significant increase in frequency during NREM sleep [74] (**Figure 1C–E**). The spikes appear only in sleep in about a third of children [97].

EEG and magnetoencephalography (MEG) studies show a stable horizontal dipole coming from the lower rolandic region with maximal electronegativity in the centrotemporal region and electropositivity in the frontal region, usually seen unilateral or bilateral [98–100]. Spikes may often appear in the central, parietal, midline, or even occipital regions which do not exclude a diagnosis of RE [98].

Somatosensory stimulation by the tapping of hands or feet or electrical stimulation of fingers at 1 Hz may activate CTS and somatosensory evoked potentials (SEPs) on the contralateral hemisphere [101].

#### *Epilepsy - Update on Classification, Etiologies, Instrumental Diagnosis and Treatment*

#### **Figure 1.**

*7y.old boy with rolandic epilepsy. (A) Interictal awake EEG. Left centrotemporal spikes with rapid spreading to the right frontal-anterior temporal region. with maximum negativity over the C3T3,F7 and maximum positivity on the right-midline frontal-parietal region F4Fp2FzPzCz(AV montage, sensitivity 20Mkv/mm, paper speed 30mm/sec, LFF 70 Hz, HFF 0.5 Hz, Rejector 50 Hz). (B) Increased paper speed clearly demonstrates propagation of left centrotemporal spikes to the right frontal-anterior temporal region (AV montage, sensitivity 20 Mkv/mm, paper speed 120 mm/sec, LFF 70 Hz, HFF 0.5 Hz, Rejector 50 Hz). (C and D) Interictal 1NREM sleep EEG. The frequency of CTS of the same distribution is increased. (E) The same EEG sample in bipolar longitudinal montage demonstrates phase reversal on both right and left centrotemporal region (C3C4T3T4).*

Brief interictal generalized bursts of 3–5 Hz slow waves with intermixed small spikes distinctive than a pattern 3 Hz spike–wave seen in CAE may observe in about 4% of patients with RE [85, 102].

Many studies have tried to identify the source of rolandic discharges using topographic analysis, source modeling techniques, dipole tracing method, magnetoencephalography (MEG), and functional MRI (fMRI) investigations [99–101, 103–106]. The functional MRI (fMRI) triggered by EEG of the rolandic spikes as well as MEG showed activation of the sensorimotor area [104], mainly in the orofacial division of the primary sensorimotor cortex [105]. However, it

#### *Rolandic Epilepsy: Self-Limited Epilepsy with Centrotemporal Spikes DOI: http://dx.doi.org/10.5772/intechopen.96148*

is challenging to distinguish the precentral or postcentral origin of CTS [103]. Ishitobi et al., suggested the precentral origin of rolandic spikes explained this theory by the continuity of cortical surface polarity from negative gyral cortex to the surface positive interhemispheric fissure based on the combination of scalp EEG and MEG [103]. Gregory and Wong analyzed 12 independent foci in 10 patients with RE assumed that the generator of a dipole discharge was located halfway between the maximum negative and positive poles, and was most likely situated at the depth of the lower rolandic fissure or Sylvian fissure [107]. The propagation pattern of rolandic spikes first studied by Jung et al., suggests that spike propagation was caused by intracortical spreading a single dipole across the central sulcus [108].

CTS are diagnostic markers of RE only in a suggestive clinical presentation [74]. It has been widely reported that 1.2 to 3.5% of normal healthy children population between 5 and 12 years old [109, 110], 6–34% of siblings and relatives of patients affected by RE [9, 111, 112], children with migraine, behavior disturbances, ADHD, variety of organic brain diseases with or without seizures, such as cerebral tumors, Rett syndrome, fragile X syndrome and focal cortical dysplasia [84, 113] also show CTS in routine EEG recording.
