**8.1 Overview**

*Epilepsy - Advances in Diagnosis and Therapy*

*7.3.3 Ictal EEG*

**7.4 Etiology**

end of the seizure [81].

without a history of infantile spasms [85].

pared with earlier prescribed drugs [86].

**7.5 Treatment and prognosis**

sleep. PFA is an essential diagnostic criterion.

[81]. Interictal abnormalities and seizures decrease in REM sleep.

EEG pattern associated with typical seizures of LGS are:

to differentiate from the interictal SSW pattern.

• "Paroxysmal fast activity" (PFA), which consists of sequences of rhythmic activity at 10–25 Hz and lasts for a few seconds (2–10 seconds) during NREM

These may be subclinical or accompanied by subtle change of axial muscle tone, which is detectable only by EMG electrodes as the ictal expression of a tonic seizure

Focal abnormalities are usually present in patients with structural lesions; they are non-specific and depend on the underlying pathology: focal or multifocal spikes, spike-waves, polyspikes, slow waves, and focal bursts of rapid rhythms.

• TS correspond to fast bilateral rhythmic spikes at 15–25 Hz. Amplitude is low at onset but increases as the discharge progresses, preponderating over the anterior areas and the vertex; occasionally diffuse slow waves follow after the

• AA is concomitant with an irregular, diffuse, high-amplitude, more or less symmetric SSW that predominates over the frontal areas. AA may be difficult

LGS is classified as genetic, structural or metabolic, or unknown. Approximately 70% of children with LGS have symptomatic. The underlying etiologies include a history of encephalitis, meningitis, tuberous sclerosis, brain malformations (e.g., cortical dysplasias), birth asphyxia, and trauma. LGS may also follow the diagnosis of West syndrome [23]. If unknown, then it can be either idiopathic or cryptogenic. Idiopathic refers to unknown etiology with the underlying cause being suspected as genetic; in contrast to cryptogenic, the underlying cause is also not known but is presumed to be structural or metabolic. The causative role of mutations in other genes (such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2) has been elucidated in recent exome studies or in case reports in patients with LGS

The long-term prognosis varies and has not improved using new AED as com-

Valproate is a first-choice drug, which has an effect in multiple seizure types including drop attacks; useful combinations are with clobazam, ethosuximide, lamotrigine, levetiracetam, topiramate, zonisamide, and rufinamide. We should avoid too many drugs as well as carbamazepine, oxcarbazepine, and vigabatrin, which may deteriorate some types of seizures. Felbamate carries the risk of aplastic

Alternative treatment options for LGS include ketogenic diet, vagal nerve stimulation (VNS) or thalamic electrical stimulation, and corpus callosotomy (CC) [87]. VNS and CC showed more than 50% reduction in seizure frequency in patients with LGS. A study showed that CC may be more beneficial than VNS only in "drop

anemia and hepatic failure and is used in exceptional cases [17].

**94**

The term "electrical status epilepticus during sleeping" which was first described by Tassinari [1] refers to the EEG pattern (continuous spike-wave complexes exclusively during non-rapid eye movement (NREM) sleep), with a spike-wave index accounting for at least 80–85% of slow sleep. Other concept, "continuous spikes and waves during sleeping" (CSWS) are considered synonymous of ESES, but indicates both, EEG features and clinical neuropsychological characteristics, of this EE [89, 90].

Encephalopathy with ESES is an EE characterized by seizures of various types and neurological deterioration in cognitive, motor, and behavioral areas. The encephalopathy is caused by a prominent activation of epileptic abnormalities during NREM sleep [11]. Anti-seizure drugs, immune modulatory agents, and surgery [91] have been used to treat conditions associated with ESES. In spite of the long-term favorable outcome of epilepsy and ESES, the prognosis is protected because of the persistence of severe cognitive and behavioral disturbances in about a half of the patients.

### **8.2 Seizures: symptoms and semiology**

ESES syndrome is manifest with epilepsy and encephalopathy:

	- Motor seizures, rare and nocturnal during the evolution of the syndrome
	- Unilateral partial motor seizures or secondary TCGS, principally occurring during sleeping
	- Rare nocturnal seizures in which AA develops during the course of ESES, often associated with negative myoclonus or atonic components leading to sudden falls

## **8.3 Electroencephalography**

### *8.3.1 Background*

During the wakefulness, it depends on the underlying etiology.

### *8.3.2 Interictal abnormalities*

During the wakefulness, the EEG is characterized by focal or multifocal slow spikes, frequently intermixed with diffuse slow spikes and waves. In some children, the interictal EEG pattern may be similar to those observed in idiopathic focal epilepsies; in other cases, a background asymmetry, the presence of polyspikes or repetitive fast spikes, or other features may indicate underlying structural pathologies (e.g., disorders of neuronal migration). These interictal EEG abnormalities may increase when ESES starts; in addition, diffuse bursts of 2–3-Hz spike-and-wave discharges may appear [11].

The typical EEG pattern consisted of continuous or sub-continuous slow spikeand-waves, at 1.5–2.5 Hz, persisting through all NREM sleep; it appears immediately after patients fall asleep. This EEG pattern is commonly observed between 4 and 14 years and develops 1 or 2 years after the onset of seizures.

The epileptic discharges can vary from mainly focal (frontal, centrotemporal, etc.) or multifocal to unilateral, or diffuse (occasionally with shifting from a unilateral to a diffuse pattern in the same patient). In the original description, a spike-wave index (SWIs), ranging from 85 to 100% and measured during overnight sleep EEG recording, was considered an essential feature for the diagnosis [92]; however, SWIs under 85% have been used for the diagnosis of ESES syndrome as well [11].

### **8.4 Etiology**

The good outcome is the rule, independent of the etiology and is observed besides cortical malformations such as multilobar polymicrogyria. ESES syndrome has been associated with a few genes including neuroserpin/SRPX2 and ataxin 1/ ATX1 [23]; most recently, pathogenic de novo involves genes previously associated with autism (MDGA2 and SHANK3), seizures (GRIN2A), or language impairment (CDH13) [93]. Furthermore, SLC9A6 mutations have been found in patients with Christianson syndrome and CSWS [94]. The reason for manifestation of ESES in most patients is not known [23].

## **9. Landau-Kleffner syndrome (LKS)**

### **9.1 Overview**

The first description of the Landau and Kleffner syndrome (LKS) is due to William Landau and Frank Kleffner, who in 1957 reported six children with different types of seizures and acquired aphasia [2]. No other descriptions were made until the 1980s, when different authors described several new cases [95].

LKS is a type of ESES syndrome which manifests with an acquired epileptic aphasia (auditory agnosia) that occurs in the child with already developed ageappropriate speech. Like ESES, LKS is characterized by epileptic EEG pattern particularly prominent during sleeping, with or without manifest clinical seizures. Although in the first descriptions LKS is not related to brain organic lesions, patients with LKS may have congenital or acquired brain lesions [11].

**97**

*Epileptic Encephalopathies in Infants and Children DOI: http://dx.doi.org/10.5772/intechopen.85378*

**9.3 Electroencephalography**

*9.3.2 Interictal paroxysmal abnormalities*

*9.3.1 Background*

Normal.

*9.3.2.1 Wakefulness*

been reported.

*9.3.2.2 Sleep*

**9.4 Etiology**

**9.2 Epileptic aphasia and seizure symptoms and semiology**

LKS appear usually from 2 to 8 years of age; almost 60% of cases have epilepsy as the first symptom, while aphasia in the rest. Aphasia is a verbal auditory agnosia with a subacute onset, followed by rapid reduction of spontaneous speech, with perseverations, paraphasias, phonological errors, and verbal stereotypies; it can progress to mutism. Aphasia frequently has a course with remissions and exacerbations, usually related to quantitative variations of paroxysmal activity during sleeping [2, 96, 97]. The duration of the language disorder is very variable, though if it persists unchanged for more than a year, spontaneous recovery is rare. After a flexible time, aphasia stabilizes and regularly recovers before adulthood [98].

Although between 70 and 80% of patients present with epileptic seizures, these tend to be rare, sometimes a single seizure, which often occurs during sleeping. The seizures present clinical heterogeneity that includes subtle motor events such as ocular flicker, ocular deviation, simple motor focal seizures, AA, unilateral motor seizures, and, eventually, GTCS. CPSs are uncommon, while tonic seizures have never been reported. The course of the epilepsy is typically benign and seizures respond excellent to AED. Seizures

High-amplitude repetitive spikes and spike-waves with variable topography over time. Unilateral discharges are more common early in the course of LKS, habitually located in the temporal regions (>50% of the children) or in the parietal-occipital regions (around 30% of the children). Generalized spike-wave discharges have also

At the beginning of sleep, epileptic discharges (ED) are also initiated. The ED can be partial, often on posterior temporal topography. Unilateral subclinical discharges can be detected alternating between both hemispheres. During the development of the disease, the EEG of the sleep will show a pattern of bilateral spike-wave activity, continuous or sub-continuous, during more than 85% of the NREM sleep time (ESES syndrome) [97]. LKS is a clinical subtype included in the

In most patients the cause of LKS remains unknown. Autoimmune etiology has been suspected because of minor immunological irregularities reported in a number of patients and because of the response of LKS patients to immunotherapy [23]. Mutations in GRIN2A (16p13.2) have been reported as a major genetic cause of LKS and of the syndrome known as epileptic encephalopathy with continuous spikes and waves during slow-wave sleep (CSWS) [99]. Children with LKS have, most

wide spectrum of the clinical manifestations of ESES syndrome.

eventually disappear over time, generally by about the age of 15 years [98].
