Lennox-Gastaut syndrome (LGS), is an age-related cryptogenic or symptomatic generalized epilepsy syndrome, a type of age-dependent epileptic encephalopathy. It is characterized by an onset in early childhood, a variety of seizure forms, usually frequent and difficult to control seizures, extensive slow (1.5-2.5 Hz) spike-and-slow wave discharges on the EEG, and impaired intellectual development. It is a severe type of epilepsy and most of them are persistent lifelong epileptic encephalopathies. The clinical and EEG characteristics of seizures in this group of patients were first studied by Lennox in 1945, and the relationship between clinical features and EEG was further investigated by Gastaut in 1966. The disease was named Lennox-Gastaut syndrome in honor of the pioneering work of the two scholars. Etiology Lennox-Gastaut syndrome is divided into symptomatic and idiopathic. Idiopathic LGS has no clear etiology. The main causes of symptomatic LGS include: perinatal brain injury, intracranial infection, cerebral dysplasia, tuberous sclerosis and metabolic diseases. LGS is generally considered to be a severe abnormal response of the immature brain in children to extensive and localized brain injury. The etiology is due to prenatal factors accounting for 10% to 15%, perinatal factors accounting for 5% to 36%, postnatal causes accounting for 10% to 25%, and unknown causes accounting for 30% to 70%, and there is controversy over the genetic factors of the disease. Clinical presentation The syndrome is an age-related epileptic encephalopathy with an age of onset of 1-8 years and a peak of 3-5 years. lennox-Gastaut syndrome accounts for 5% to 10% of childhood epilepsy. About 20% of children present with infantile spasms prior to the onset of the disease. lGS is often associated with varying degrees of mental retardation, which is present in about 20%-60% of patients at onset and in 75%-90% of patients several years after onset; however, previously acquired psychomotor functions do not diminish with disease progression, unlike other degenerative encephalopathies. Mental retardation is associated with early and late onset. Half of the patients have behavioral abnormalities, mostly ADHD, and other abnormalities such as aggressive, disruptive, and excessive sexual behavior may also be present. About half of the patients have no deficits in neurological examination and imaging, while the rest may have various degrees of neurological deficits, such as cerebral palsy, speech abnormalities, etc. The most common types of seizures are tonic seizures, atypical aphasic seizures and atonic seizures. Myoclonic, generalized tonic-clonic seizures and partial seizures can also be seen. 1. Tonic seizures are characterized by sudden tonic contractions of certain muscles, fixed in a certain posture, lasting for a period of time, with a brief loss of consciousness and wakefulness after the seizure, which is not easy to form a series of seizures. Tonic seizures and their EEG-specific changes are one of the main features of LGS. Body-axis tonic seizures, limb-axis tonic seizures and generalized tonic seizures can occur both during the day and at night. Bilateral limb manifestations may be symmetrical or asymmetrical during seizures. In young children, seizures often occur during wakefulness, while in children with late onset, there is a tendency to have brief tonic seizures during slow-wave sleep and an increased number of seizures during deep sleep. If the seizure is brief, sometimes it can only be seen on EEG video monitoring, which shows slow limb straightening, eye rolling and changes in respiratory rhythm; if the seizure lasts more than 20 seconds, the child will have a generalized rapid small-amplitude clonic; loss of consciousness is not a characteristic of this seizure; sometimes oropharyngeal or behavioral automatism is seen before or after the seizure; the seizure may be accompanied by enuresis and pupil dilation. The EEG during seizures shows a generalized fast rhythm (10 Hz) emission. This may be preceded by transient EEG hypoarousal and, if accompanied by automatism, by widespread slow spike-slow waves following the fast rhythm. 2. atypical aphasic seizures manifest as momentary bouts of daze, fogginess, double vision, movement cessation, and a tendency to appear periodically. Atypical aphasic seizures are seen in 50% to 80% of children with LGS. The seizures begin and end gradually and are sometimes difficult to observe clinically. When consciousness is not completely lost, the child can still perform simple activities. Atypical aphasic seizures often affect the muscle tone, causing it to decrease and fall. If the decrease in muscle tone occurs in the face and neck muscles, the patient may show sudden forward head tilt, open mouth, and salivation. The EEG during the seizure is a wide irregular 2-2.5 Hz slow spike-slow wave, and the bilateral cerebral hemisphere discharges may be symmetrical or asymmetrical. Atypical aphasic seizure persistence: Seizures occur continuously with cloudy consciousness, during which there may be akathisia, transient generalized myoclonic seizures, etc., also known as petit mal seizure persistence, seen in 14%-50% of LGS patients. 3. Atonic seizure is a transient loss of muscle tone, and can not maintain the posture, the seizure lasts 1 to 3 seconds, sometimes several seizures in a row. Myoclonic seizures are sudden, rapid jerking of the face, trunk or limbs, mostly single jerking, or repeated jerking. The seizures are not accompanied by impairment of consciousness and can occur at any time. Seizures can be triggered by stimuli. All three types of seizures can cause sudden head or body collapse and are clinically indistinguishable from each other. The precise diagnosis depends on the muscle activity tracing, i.e., the synchronized EMG activity in EEG monitoring. Its EEG may show slow multi-spike – slow wave, slow spike – slow wave or fast rhythm discharges with predominance of the anterior head. A brief spasm is seen at the end of the seizure, and its clinical features are similar to those of myoclonus. The child may have one or several forms of seizures at the same time, with tonic seizures being the basic type of seizure, which can also transform from one seizure form to another during the course of the condition. The predominance of one form depends on the age of the child (transient spasms are common in young children), the etiology (atypical aphasic seizures with falls and dystonic seizures are common in children with no obvious etiology before the illness) and the state of consciousness (tonic seizures are often seen during sleep). EEG examination: the characteristic EEG changes have diagnostic significance. The EEG performance varies in different waking states, with continuous slow spike-slow wave distribution during wakefulness (mostly atypical aphasic seizures), more slow waves during sleep than during wakefulness and persistent; paroxysmal fast rhythms during slow wave sleep (mostly tonic seizures); abnormal background activity, showing a decrease in the posterior fundamental rhythm or absence, varying degrees of slowed activity and asymmetry. Slow spike and wave activity helps to differentiate the (poorly prognostic) Lennox-Gastaut syndrome from benign absence epilepsy, which is characterized by diffuse 3-Hz spike and wave activity, and from benign myoclonic epilepsy with fast spike and wave. Myoclonic types of epilepsy (which has a much better prognosis than Lennox-Gastaut syndrome). However, there are many other epilepsy syndromes with waveforms similar to Lennox-Gastaut syndrome, including Doose and other severe myoclonic epilepsies. 2. cranial CT, MRI: About 75% of children with LGS have neuroimaging examinations that do not reveal any abnormalities. Diagnosis LGS presents with multiple seizure forms and can be interconverted, making the diagnosis difficult. The possibility of this syndrome should be considered in refractory epilepsy with multiple seizure types in childhood. The diagnosis can be made by taking a detailed history of the child’s past history and seizure patterns (multiple seizure types are present at the same time, the most common forms being tonic, atypical aphasic, and atonic seizures), combined with characteristic EEG changes during the waking and sleeping periods, and the development of hypo-intelligence and personality changes as the disease progresses. Differential diagnosis Late onset West syndrome: Both syndromes have the same etiology, both have intellectual disability, and some children with West syndrome may develop into LGS after several years. In this case, special attention should be paid to the follow-up of the EEG. Doose syndrome: In children aged 2-5 years, convulsions begin with marked myoclonus, myoclonic dystonic and atonic seizures, without tonic seizures, and there may be non-convulsive epileptic continuity with different features of EEG, fast-spike complex waves and slow-spike complex waves, suggesting Doose syndrome. In the second stage of the disease evolution, some of these children develop tonic seizures with a presentation that fully meets the diagnostic criteria for LGS, making early differentiation very difficult. If a child with LGS presents only with atypical aphasic seizures with automatism, it needs to be differentiated from temporal lobe epilepsy, which is not associated with intellectual impairment and does not have the characteristic EEG changes of LGS. Treatment This disease is one of the most difficult to treat childhood epilepsy syndromes. The efficacy of antiepileptic drugs is unsatisfactory, drug efficacy is short-lived, rarely lasting 1 year, and seizures are not controlled in 80% to 90% of children. A 50% reduction in seizures may be the desired treatment outcome. Because of frequent seizures, often resistant to antiepileptic drugs, often due to the tendency to use multiple drug therapy, prone to toxic effects of drugs, and the sedative effect produced by multiple drugs actually increases the frequency of seizures, it is ideal to choose a single antiepileptic drug therapy. Antiepileptic drugs are primarily chosen based on attempts to control those major, most severe seizure types. Sodium valproate is a broad-spectrum antiepileptic drug effectively used to treat tonic seizures, atypical akathisia, myoclonic and tonic-clonic seizures. In children with atonic or tonic seizures, sodium valproate is more effective than other antiepileptic drugs. Clonazepam is more effective for myoclonic seizures. Sodium valproate can be combined with clonazepam to treat patients with both atonic and myoclonic seizures. Other drugs may also be effective, including: topiramate, lamotrigine, carbamazepine, phenytoin sodium, phenobarbital, acetazolamide. ACTH can only temporarily reduce seizures. Some children are effective with corpus callosotomy. A ketogenic diet may be used for those who fail to respond to pharmacological treatment. Prognosis The prognosis for this syndrome is poor, with a poor quality of life. A small number of LGS have a resting course, and cognitive function may improve if seizures are controlled. the mortality rate of LGS is about 4% to 7%, mostly due to persistent status epilepticus.