**7. Lennox-Gastaut syndrome (LGS)**

### **7.1 Overview**

LGS is an electroclinical syndrome defined by the Marseille School between 1966 and 1972 but was first reported by Lennox and Davis as an epilepsy starts in childhood and characterized by diffuse slow spike-waves (SSW) at <2.5 Hz and several types of seizures including tonic seizures, atypical absences, and "drop attacks" [81]. The electroclinical description proposed by Beaumanoir and adopted by the ILAE Classification Commission in 1989 concerns 2–4% of childhood epilepsies and affects boys more frequently than girls [81]. In about 70–75% of patients, LGS is associated with a variety of inherited or acquired structural anomalies or chromosomal disorders, whereas in the other 25–30%, there is no identifiable etiology [82]. Electroclinical phenotype is similar in spite of the different etiologies because of a common underlying mechanism [83]; functional neuroimaging has indicated that epileptic activity in LGS recruits widespread areas of association cortex and that tonic seizures are expressed through the reticular formation of the pons [84]. Other epileptic syndromes like frontal epilepsies with secondary bilateral synchrony, EMAS, DS, late-onset ES, atypical benign partial epilepsy of childhood, and ring chromosome 20 epilepsy syndrome are the differential diagnoses; thus, an exhaustive evaluation of the medical history along with an EEG during the wakefulness and sleep is very important for the accurate diagnosis of the syndrome.

### **7.2 Seizures: symptoms and semiology**

Seizures start from 1 to 10 years but more frequently between 1 and 8 years; however, onset may occur in younger or older ages, even into adulthood. LGS may follow other types of epileptic syndromes, such as focal epilepsies, OS, and WS.

Diagnosis of LGS requires the following features: (1) many types of seizure, but inevitably include tonic seizures (TS) and atypical absences (AA), (2) cognitive impairment, and (3) typical interictal and ictal EEG patterns.

**93**

to a fall.

polygraphic recording.

**7.3 Electroencephalography**

*7.3.2 Interictal abnormalities*

for diagnosis of LGS [11].

usually have little influence on the SSW activity. Characteristic features during sleeping are:

*7.3.1 Background*

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

TS are mandatory for the diagnosis of LGS; they are diurnal and nocturnal, facilitated in NREM sleep, and typically occur in clusters. TS consist of sudden flexion of the neck and body, raising of the arms in flexion or extension, extension of the legs, and contraction of the face muscles. It continuing of the eyes and autonomic manifestations (apnea and facial flushing tachycardia), and can culminate as diffuse tremor (rapid, small-amplitude jerks affecting the whole body). They are axial and involve typically the proximal parts of the limbs, symmetrically or with unilateral predominance. TS can produce sudden falling, associated or not with

AA is the second most common seizure, present in about 75% of patients. The main clinical manifestation is a brief lapse in consciousness, although some awareness may be preserved [82]; they are subtle and difficult to recognize without concurrent formal assessment of cognition and responsiveness. They are of long duration with the EEG discharge lasting >20 seconds, but their onset and termination are not always clinically discernible. Associated clinical features may include eyelid and mouth myoclonias and a decrease in muscle tone that may lead

"Drop attacks" (sudden falls) are also frequent, affect 30–60% of patients, and are habitually related with a brief tonic seizure or an epileptic spasm [81]; the definition of seizure type that cause sudden falls most be requiring Video-EEG and

with continuous SSW, and may be linked with serial tonic seizures [83].

Drop attacks, and other types of seizures observed in LGS, are not specific to this syndrome; these are tonic-clonic, focal, myoclonic, and myoclonic-atonic. Episodes of SE may occur in about 60% of patients, consisting of alteration of consciousness

EEG is variable depending on etiology (structural, chromosomal, or idiopathic) and age, ranging from almost normal to, most often, poorly structured without physiological features and generally altered by continuous interictal abnormalities.

Generalized interictal features during the wakefulness and sleep are mandatory

In wakefulness, high-amplitude, diffuse, and synchronous SSW at 1.5–2.5 Hz is typical. Slow SSW has maximal amplitude over frontal areas and ranges in duration from a few seconds to a few minutes or sub-continuous. The complexes typically consist of a spike (duration < 70 ms) or a sharp wave (70–200 ms), followed first by a positive deep and then by a negative wave (300–500 ms) [81]. Such stimuli, as eye opening, noise, calling the patient's name, and pain, tend to decline the occurrence or terminate SSW [81]; on the other hand, relaxation and drowsiness favor their occurrence. Hyperventilation (HV) and intermittent photic stimulation (IPS)

• SSW discharges that are activated during slow sleep, with more marked

• Bursts of high-amplitude generalized polyspikes and polyspike-waves.

tendency toward bilateral synchrony than in wakefulness.

brief loss of consciousness; the distal limb muscles are relatively spared.

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

*Epilepsy - Advances in Diagnosis and Therapy*

been found consistently in sporadic cases [79].

**7. Lennox-Gastaut syndrome (LGS)**

**7.2 Seizures: symptoms and semiology**

Patients with Doose syndrome have probably a multifactorial inheritance, some of the first to be diagnosed with SCN1A mutations, but others have also been found to have sodium channel subunit beta-1 (SCN1B) and gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2) mutations. However, these genes have not

Ethosuximide is reported to be one of the more effective antiepileptic drugs (AED), especially when absence seizures are the primary seizure type. Valproic acid and lamotrigine are also beneficial; however, lamotrigine probably cause paradoxical worsening in individuals for whom myoclonic seizures are prominent [79]. Levetiracetam and zonisamide have been anecdotally used and may be helpful [23]. The ketogenic diet is a widely reported therapy for Doose syndrome and may be the most efficacious treatment; expert consensus guideline for optimal use of the ketogenic diet listed Doose syndrome as one of the principal indications for this treatment [79]. Seizure remission has been reported even without changes to medication, which suggest that spontaneous remission of seizures does occur.

LGS is an electroclinical syndrome defined by the Marseille School between 1966 and 1972 but was first reported by Lennox and Davis as an epilepsy starts in childhood and characterized by diffuse slow spike-waves (SSW) at <2.5 Hz and several types of seizures including tonic seizures, atypical absences, and "drop attacks" [81]. The electroclinical description proposed by Beaumanoir and adopted by the ILAE Classification Commission in 1989 concerns 2–4% of childhood epilepsies and affects boys more frequently than girls [81]. In about 70–75% of patients, LGS is associated with a variety of inherited or acquired structural anomalies or chromosomal disorders, whereas in the other 25–30%, there is no identifiable etiology [82]. Electroclinical phenotype is similar in spite of the different etiologies because of a common underlying mechanism [83]; functional neuroimaging has indicated that epileptic activity in LGS recruits widespread areas of association cortex and that tonic seizures are expressed through the reticular formation of the pons [84]. Other epileptic syndromes like frontal epilepsies with secondary bilateral synchrony, EMAS, DS, late-onset ES, atypical benign partial epilepsy of childhood, and ring chromosome 20 epilepsy syndrome are the differential diagnoses; thus, an exhaustive evaluation of the medical history along with an EEG during the wakefulness

and sleep is very important for the accurate diagnosis of the syndrome.

impairment, and (3) typical interictal and ictal EEG patterns.

Seizures start from 1 to 10 years but more frequently between 1 and 8 years; however, onset may occur in younger or older ages, even into adulthood. LGS may follow other types of epileptic syndromes, such as focal epilepsies, OS, and WS. Diagnosis of LGS requires the following features: (1) many types of seizure, but inevitably include tonic seizures (TS) and atypical absences (AA), (2) cognitive

**6.4 Etiology**

**6.5 Treatment**

**7.1 Overview**

**92**

TS are mandatory for the diagnosis of LGS; they are diurnal and nocturnal, facilitated in NREM sleep, and typically occur in clusters. TS consist of sudden flexion of the neck and body, raising of the arms in flexion or extension, extension of the legs, and contraction of the face muscles. It continuing of the eyes and autonomic manifestations (apnea and facial flushing tachycardia), and can culminate as diffuse tremor (rapid, small-amplitude jerks affecting the whole body). They are axial and involve typically the proximal parts of the limbs, symmetrically or with unilateral predominance. TS can produce sudden falling, associated or not with brief loss of consciousness; the distal limb muscles are relatively spared.

AA is the second most common seizure, present in about 75% of patients. The main clinical manifestation is a brief lapse in consciousness, although some awareness may be preserved [82]; they are subtle and difficult to recognize without concurrent formal assessment of cognition and responsiveness. They are of long duration with the EEG discharge lasting >20 seconds, but their onset and termination are not always clinically discernible. Associated clinical features may include eyelid and mouth myoclonias and a decrease in muscle tone that may lead to a fall.

"Drop attacks" (sudden falls) are also frequent, affect 30–60% of patients, and are habitually related with a brief tonic seizure or an epileptic spasm [81]; the definition of seizure type that cause sudden falls most be requiring Video-EEG and polygraphic recording.

Drop attacks, and other types of seizures observed in LGS, are not specific to this syndrome; these are tonic-clonic, focal, myoclonic, and myoclonic-atonic. Episodes of SE may occur in about 60% of patients, consisting of alteration of consciousness with continuous SSW, and may be linked with serial tonic seizures [83].
