Introduction

Lennox-Gastaut syndrome is a severe, lifelong, treatment-resistant form of epilepsy that develops during childhood. Usually begins before eight years of age, with most children developing the syndrome between the ages of three and five years old.¹

The incidence of this syndrome accounts for approximately 1 to 2 % of all epilepsy cases in all age groups, and nearly 10% of epilepsy cases in children less than 5 years old. Lennox-Gastaut syndrome tends to affect assigned male at birth (AMAB) more than assigned female at birth (AFAB).²

The exact cause of Lennox-Gastaut syndrome varies between individuals, ranging from no identifiable cause to genetic, injuries or infection. It is typically characterised by intellectual disability and treatment-resistant epileptic seizures of varying types, among those who suffer from the syndrome.^2,4 

The presence of treatment-resistant seizures, with age of onset occurring before 18 years of age, and thorough history taking and diagnostic findings, such as brain scans (e.g. MRI or EEG), are crucial for diagnosing the syndrome. It further determines the cause for appropriate, early treatment and seizure management.^1,3

Clinical presentation of Lennox-Gastaut syndrome

The clinical presentation of Lennox-Gastaut syndrome is described by the characteristic triad of multiple, varied seizure types, characteristic findings on a brain electrical activity scan called the EEG, and intellectual disabilities. These typical clinical findings may not necessarily all be present during the early stages of the disease, therefore, recognition and diagnosis can be complex and challenging.^5,6

Seizures

Seizure types in Lennox-Gastaut syndrome typically begin in childhood and are nonspecific, with individuals presenting with multiple, varied types of seizures. The most common ones being tonic seizures and atypical absence seizures, followed by myoclonic seizures, atonic seizures, nonconvulsive status epilepticus and generalised tonic-clonic seizures. Each seizure type has its clinical presentation.^6,7

Tonic seizures

Tonic seizures are a classic, typical clinical presentation of Lennox-Gastaut syndrome. This type of seizure is characterised by:

• A sustained muscle stiffening in the arms, legs, head, neck and trunk
• Seizures typically last seconds to a few minutes, most often occurring during sleep, or sometimes during the early period of waking up
• An individual must suffer from tonic seizures to be diagnosed with Lennox-Gastaut syndrome

Atypical absence seizures

These are the second most common type of seizure seen in people suffering from Lennox-Gastaut syndrome. Symptoms of someone suffering from this seizure type include:

• A period of ‘absence’ where an individual has a gradual, brief, reduced state of awareness
• Seizures typically last 5 to 30 seconds
• It is sometimes difficult to notice a seizure in people with other cognitive behavioural issues

Atonic seizures

This seizure type is seen in around 10-56% of individuals with Lennox-Gastaut syndrome, and is typically characterised by a sudden ‘drop attack’ due to a loss of muscle tone affecting the head, neck and trunk region responsible for stability. People with these seizures suffer from multiple falls and injuries, therefore, controlling them is key to preventing the risk of serious injuries.

Myoclonic seizures

Myoclonic seizures are a severe form of epilepsy that begins at a very young age. They are brief, shock-like muscle jerks and often affect the upper arms, shoulders and face. 

Nonconvulsive status epilepticus

Most patients will experience nonconvulsive status epilepticus (NCSE) at some stage after their diagnosis of this syndrome. It is continuous seizures up to 30 minutes and can result in further developmental and intellectual impairments. Symptoms of this type of seizure include:

• Staring spells
• Feeling sissy
• Non-responsiveness

The frequency of onset of seizures not only varies between different people, but also within themselves. People can suffer from alternating periods of frequent-onset seizures to seizure-free periods as well.^6,7  

Neurological, cognitive, behavioural, and motor impairments

Motor, neurological, behavioural and cognitive symptoms vary in different children with Lennox-Gastaut syndrome. Some may have normal growth and no brain development abnormalities before the start of the syndrome, while others may show delays in brain development even before the onset of symptoms of seizures. 

Most individuals suffering from Lennox-Gastaut syndrome will experience a degree of cognitive or behavioural impairment. This could be development delays, impaired intellectual functioning and learning difficulties and behavioural problems such as aggressive behaviour patterns or hyperactivity, disturbances in sleep, and may even have autism spectrum disorder (ASD).

Ultimately, many children will reach a developmental plateau and may even show a reversal in achieving important developmental milestones. This decline is becoming increasingly noticeable and worsening as they grow older.^7,8,9

Diagnostic criteria of Lennox-Gastaut syndrome

Causes

Lennox-Gastaut syndrome occurs as the result of a wide range of underlying causes. These vary from: 

• Genetic disorders
• Brain injuries
• Brain tumours
• Infectious causes, such as meningitis
• Malformations in the structure of an area of the brain, called the cortex (cortical malformations)

However, in nearly half the cases of Lennox-Gastaut syndrome, no obvious or identifiable cause is found, this is called idiopathic Lennox-Gastaut syndrome.^4,10

Clinical evaluation in diagnosing Lennox-Gastaut syndrome

The syndrome is defined by three findings, these are:

• Multiple, varied types of seizures
• Findings on the brain scans
• Intellectual disabilities

However, diagnosis of Lennox-Gastaut syndrome is challenging, especially in the early stages of the syndrome, because these hallmark clinical findings and changes on the electroencephalogram (EEG) may not be present.⁵

Therefore, to diagnose a person with Lennox-Gastaut syndrome, a thorough assessment is required, which includes an in-depth history that examines prenatal, birth, and various medical, behavioural, and developmental milestones, along with a detailed record of all seizure occurrences.

History taking is followed by a thorough medical examination, including blood tests, and an EEG scan of the brain. There are mandatory criteria someone must exhibit in their history and physical exam to be diagnosed with Lennox-Gastaut syndrome.⁷

Mandatory diagnostic criteria

Multiple seizure types

People must have the presence of tonic seizures, and at least one other type of seizure, which could vary between atypical absence seizures, myoclonic, atonic, generalised tonic-clonic seizures or nonconvulsive status epilepticus. These seizures must begin in individuals at age 18 or younger and are resistant to medication.⁵

Intellectual disability

Often at diagnosis, and increasingly with age, people will display intellectual disability, which could range from mild to severe.^11,9

Electroencephalogram (EEG) abnormalities

An EEG scan will show a particular brain wave pattern for diagnosis. Often, a scan will be performed both when someone is asleep and when awake, but changes are often seen on the scan in sleep.^5,7

Diagnosis

Clinical signs and symptoms of Lennox-Gastaut syndrome will typically change over time, therefore, sometimes, establishing a clear diagnosis will require multiple follow-ups in the clinic, which could take years.

Diagnosis is essential to try and improve seizure control, which is a very severe challenge in Lennox-Gastaut syndrome. This can result in severe complications, particularly in those with poor control in their first years of diagnosis, as seizures can result in brain injuries and accidents as a result.¹¹

Summary

Lennox-Gastaut syndrome is a serious, life-long form of epilepsy that develops in children. People with Lennox-Gastaut syndrome suffer from multiple, varied, treatment-resistant seizures, which typically begin in early childhood. There are various types of seizures a person can have, and in Lennox-Gastaut syndrome, the person must suffer from tonic seizures, in addition to one other type of seizure, which could be atonic, myoclonic, generalised tonic-clonic or non-convulsive status epilepticus seizures, among others. Additionally, these children will present with intellectual disabilities, growth and developmental impairments or delays. Some could present normally during the onset of seizures, while others can show the signs of these delays and disabilities even before the onset of seizures. These will commonly be aggressive behaviour patterns, hyperactivity, autism spectrum disorder, sleep difficulties and learning difficulties. Most will experience worsening developmental symptoms as they age. These children will demonstrate characteristic changes of Lennox-Gastaut syndrome on a brain scan called the EEG. Diagnosis of Lennox-Gastaut syndrome can be difficult due to the nature of the clinical presentation. These three characteristic clinical findings are required for diagnosis of the disease, however, they may not all be present during the early stages of the disease. Therefore, for some, diagnosis will require multiple clinical follow-ups over a prolonged period of time for a definitive diagnosis.

A clear diagnosis is essential as management of Lennox-Gastaut syndrome is complicated, requiring a thorough, individualised treatment pattern for life. Treatment will focus on achieving the best control of seizures, to prevent the progression to severe complications, such as brain injuries, and focus on improving a person's quality of life effectively.