What Is Lennox-Gastaut Syndrome

Overview

Lennox-Gastaut syndrome is a type of epileptic disorder whose symptoms usually appear during childhood. Recently, it has been classified as an age-related disorder.¹ It is commonly associated with three main symptoms: recurrent seizures, defined neuronal activation waves, which can be recorded with electroencephalogram (EEG), and cognitive deficits. The syndrome can result from a pre-existing brain disorder, or its origin can be unknown.² In this article, the syndrome will be evaluated by highlighting its causes and defining symptoms. In addition, the diagnosis and treatment will be discussed. The latter part will reflect the controversies surrounding Lennox-Gastaut syndrome, which is challenging to diagnose, mainly due to the difficulty encountered in the past years in reaching a consensus definition of the disorder and its diagnosis, as well as the lack of clinical trials to propose convincing treatment strategies.¹ 

Causes of lennox-gastaut syndrome

The causes of Lennox-Gastaut syndrome can be divided into two main groups: cases where causes are identifiable and those where the causes are not identifiable, also known as cryptogenic. The identifiable causes include head trauma, birth complications, pre-birth malformations, infections such as sepsis and meningitis, and metabolic problems. Unknown causes of the disease are found only in 25-35%, and no unique genetic mutation is linked to the syndrome.³ 

Signs and symptoms of lennox-gastaut syndrome

The signs of Lennox-Gastaut syndrome include seizures, abnormal neuronal activity patterns detected through wave recordings, and impaired cognition. The cognitive symptoms manifest gradually at the onset of the syndrome in children. As seizures begin to occur, EEG recordings detect abnormal wave patterns, initially only during the child is awake and gradually during sleep as well. These abnormal neuronal firing patterns during the critical period of child development characterise cognitive impairment in the disease.² 

Over time, the epileptic attacks may decrease, but Lennox-Gastaut syndrome is a chronic disorder. Consequently, the intellectual disabilities that result from frequent seizures during the early years tend to worsen. Only 10-20% of children maintain cognitive functions within an acceptable range, while in 20-60% of cases, some forms of intellectual disabilities present due to brain malfunctions. For this reason, in cases of the cryptogenic form of the syndrome, we observe that the brain development before the onset of the first seizures does not seem to be impaired for most people.² 

Management and treatment for lennox-gastaut syndrome

As we are considering a rare syndrome, the number of clinical trials evaluating the treatment of Lennox-Gastaut syndrome specifically is very low, with only 6 trials conducted in total by last year (2022). It is also difficult to compare patients using different treatment strategies, as the seizures they experience are classified into different groups, and not all of them are clearly visible and recognisable.¹ This makes treatment comparison among patients observer-dependent and hinders the development of an objective measurement scale to determine the best strategy for managing the syndrome.

The main signs of the syndrome are recurrent seizures, which can be managed through anti-epileptic drugs, surgeries that prevent the spread of abnormal waves in the brain, and non-anti-epileptic drug treatments, such as ketogenic diets and deep brain stimulation.¹  

Anti-epileptic treatment

To treat seizures, one of the most used drugs since the 1970s is benzodiazepines (BDZs), which are effective in reducing the spread of abnormal neuronal activity by activating gamma-aminobutyric-acid (GABA) transmission.⁴ There are different types of BDZs available, and the treatment strategy must be carefully planned because some BDZs are not suitable for prolonged use, as they may cause side effects. Newer anti-epileptic drugs, which act on different sites than BDZs, are sometimes prescribed as adjunctive therapies to improve the treatment. However, in this type of therapy, additional attention needs to be paid to avoid unpleasant or dangerous drug interactions, as the circulation and action of BDZs in our body can be affected by the administration of adjunctive anti-epileptic drugs. In the case of cryptogenic Lennox-Gastaut syndrome, vitamin B6 is also given as part of the therapeutic treatment, as it aids mitochondrial function, whose impairment is linked with seizures.¹ 

Surgery

The main type of surgery used to treat epileptic disorders is callosotomy, a procedure in which the corpus callosum, the large white matter tract connecting the left and right brain, is surgically removed.⁵ This reduces the spread of the epileptic waves in the brain; however, its efficacy ranges greatly between 40 to 80%, depending on the type and extension of the brain disconnection. Due to the rarity of Lennox-Gastaut syndrome, there is not enough data to understand whether this type of surgery is effective for the syndrome. Some Lennox-Gastaut syndrome patients seem to become seizure-free after resection of parts of the cortex rather than the corpus callosum, but perhaps the outcome depends on the pre-surgical disease evaluation of each patient.¹ It is important to note that resection of cortical parts can have a negative impact on other brain functions. Therefore, another type of surgery, multiple subpial transection, which does not involve the removal of cortical areas, has been used, and this technique has dramatically improved the symptoms in some anecdotal cases. Before surgery, especially before callosotomy, vagal nerve stimulation is often recommended. Other nerve-stimulating options, like deep brain stimulation, seem to have general beneficial effects on Lennox-Gastaut syndrome patients. In general, surgical and stimulation techniques are palliative in the treatment of epilepsy, meaning that they are not able to eliminate the disorder and the associated seizures.

Non-anti-epileptic treatment

Alternative treatment strategies include immunotherapies and diet. Many studies have linked the immune system with epileptic disorders, and some drugs that improve immune function or antibody treatments have been used in these disorders. However, in the specific case of Lennox-Gastaut syndrome, there have not been enough trials to show that immunotherapies administered within the first year of syndrome development in children are able to improve the condition. Therefore, the effectiveness of this strategy is considered more theoretical than practical. In regard to diet, the ketogenic diet and the effect of fasting appear to improve seizure attacks. However, it must be considered whether this type of complementary treatment strategy is suitable and sustainable for children.¹ 

When it comes to treatment, numerous strategies offer potential improvement for the patient's condition. However, none of these strategies can entirely eliminate the symptoms of the condition or halt the increasing frequency of seizure attacks as the syndrome progresses. Moreover, due to limited trials focusing on identifying the optimal treatment strategy for Lennox-Gastaut syndrome, there is currently no universally agreed-upon management approach for the syndrome.

Diagnosis

The main problem with diagnosis is that Lennox-Gastaut syndrome shares symptoms with other epileptic disorders. In addition, the range of seizure types that differentiate Lennox-Gastaut syndrome is divided into three types, and their frequency might differ. 

• Tonic seizures: These are defined as prolonged muscle contractions lasting several seconds or minutes and are essential to diagnose Lennox-Gastaut syndrome
• Atonic seizures: These occur secondary to tonic seizures and are experienced by Lennox-Gastaut syndrome patients. These atypical seizures entail lapses of consciousness that are more difficult to identify compared to the convulsive states observed in tonic seizures. Moreover, between 50 to 75% of patients also exhibit a non-convulsive status epilepticus, a continuous form of atypical seizures that are occasionally interspersed with tonic seizures²
• Myoclonic seizures: They present shorter forms of tonic seizures, causing sharp, uncontrollable muscle movements in some or all of your body. While typically lasting less than a second, many myoclonic seizures can occur within a short timeframe

In general, these types of epileptic seizures define the diagnosis of the syndrome, alongside cognitive decline and impaired brain waves. Concerning brain waves, Lennox-Gastaut syndrome is recognisable by slow wave patterns and sudden bursts of neuronal activity, which constitute the abnormal neuronal communication pattern underlying the seizure attacks. Their recording through an EEG can aid in diagnosing the syndrome.

FAQs

How can I prevent lennox-gastaut syndrome?

Often, Lennox-Gastaut syndrome in children develops from other epileptic syndromes, such as West syndrome, which refers to a constellation of seizures and spasmodic symptoms in infants.⁶ In a study involving 98 patients with West syndrome, aimed at analysing the development of symptoms into Lennox-Gastaut syndrome, it appeared that the risk of developing Lennox-Gastaut syndrome was lower when anti-epileptic drugs were combined with a ketogenic diet and hormonal therapies, including drugs such as prednisolone and adrenocorticotropic hormone.⁷ Therefore, it appears that the modulation of diet or hormones, or the combination of these two factors, can be used in the prevention of Lennox-Gastaut syndrome in infants exhibiting seizure or spasm symptoms. 

How common is lennox-gastaut syndrome?

Lennox-Gastaut syndrome is a rare type of epileptic syndrome, accounting for only 1-2% of the population with epileptic disorders and 1-10% of infants with such disorders. It is more common in males than in females, with a ratio of 6:1.³ 

Who is at risk of lennox-gastaut syndrome?

• Infants with other epileptic disorders, such as West syndrome, who exhibit seizures or spasms, are at risk of developing Lennox-Gastaut syndrome⁶
• The syndrome often results from infections, birth complications, head traumas, encephalopathies, and other forms of brain injuries
• The syndrome typically appears in children, with a statistical peak at 35 months after birth. The onset range of Lennox-Gastaut syndrome spans from the tenth day of life to nine years
• The cryptogenic form of Lennox-Gastaut syndrome seems to manifest earlier than in cases where the syndrome appears secondary to other diseases³ 

When should I see a doctor?

Seizures are impairing symptoms of epileptic disorders, and when they occur in young children, they can irreversibly affect normal brain development during growth. It is, therefore, important to seek medical attention as soon as these symptoms appear. Seizures can manifest in various forms, so it is crucial to discuss any abnormal movements and behaviours observed in children with a doctor.

Summary

Lennox-Gastaut syndrome is a rare type of epileptic disorder that affects children during their developmental years and can consequently lead to impaired cognition later in life. Due to the low prevalence of the disorder, there have been limited studies to determine the most effective treatment. Brain surgery has shown improvement in some cases, while drug treatments mainly aim to control seizure attacks. Preventing the disorder is crucial, especially in cases where other brain-damaging conditions are present, as Lennox-Gastaut syndrome often develops from these or other epileptic syndromes like West syndrome. The consequences of Lennox-Gastaut syndrome are severe, both in terms of recurrent seizure attacks and subsequent cognitive impairment. It is imperative that more studies in the coming years compare therapies for Lennox-Gastaut syndrome to identify the best treatment and management strategies. Early identification of the syndrome is vital to preserve the cognitive abilities of affected children.

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If you are interested in up-to-date news on the Lennox-Gastaut syndrome ongoing research, or further information on the syndrome management, visit the website of the Lennox-Gastaut Foundation.