Overview

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy. It was first named by Lennox as “Petit mal variant”. It was later named after him in 1966 by Gastaut and his coworkers as Lennox-Gastaut syndrome. Seizures begin in early childhood, usually before the age of 4 years. It typically begins before age 8, with peak onset between the ages of 3 and 5. A recent study estimates LGS has occurred between 14.5 and 28.0 per 100,000 individuals, with a prevalent rate ranging from 5.8 to 60.8 per 100,000 individuals. Additional research suggests that LGS accounts for 1% to 2% of all epilepsy cases, 2% to 5% of childhood epilepsies, and 10% of epilepsy cases in children aged 5 or younger. LGS is slightly more common in males, with no apparent link to specific ethnic backgrounds.^{1, 2,3} 

What is Lennox-Gastaut syndrome(LGS)? 

Lennox-Gastaut syndrome (LGS) is one of the eight syndromes under epileptic encephalopathy, as reported by the International League Against Epilepsy (ILAE) task force. It is a lifelong, severe developmental epileptic encephalopathy characterised by treatment-resistant epilepsy, intellectual disability, and multiple seizure types, most notably tonic, atypical absence, and atonic seizures.^2,3

Comorbidities in Lennox-Gastaut syndrome

Intellectual disabilities(ID)/cognitive impairment 

LGS is identified by the occurrence of frequent seizures, which include mainly atonic, tonic, and atypical absence seizures. This leads to behavioural disorders and intellectual disabilities. 20–60% of LGS patients have cognitive impairment before the onset of seizures, particularly when LGS has a definite cause of occurrence. Children with LGS in whom the origin of occurrence is unknown may seem to develop normally before the appearance of the first seizures. In general, cognitive impairment becomes increasingly notable over time, and after the onset of the seizures, the proportion of patients with serious ID may increase to 75–95% by 5 years of the patient's age. The cognitive outcome of patients with LGS is not constant, and there is no proof that it is directly proportional to the severity of the epilepsy episodes. About one-third of people with LGS have normal intellectual development before seizures begin, while the rest have intellectual disability or learning problems even before seizures arise. If seizures are very frequent or severe, then ID will worsen over time.^3,4,5

Behavioural issues

Cognitive impairment is most of the time associated with social–emotional problems, but there is not necessarily a direct connection between the severity of the cognitive disability and the frequency of behavioural difficulties. Common behavioural issues in LGS patients include hyperactivity, inattention, anxiety, depression, agitation, aggression and sometimes autism.^{4 6}

Autism spectrum disorder

Autism, also known as autism spectrum disorder (ASD), is a lifelong developmental condition that influences how a person communicates, interacts, and processes information. It has been suggested that factors involved in the pathogenesis of autistic traits in LGS are the epilepsy itself, abnormal brain neural network characteristics, the effect of medications, along with cognitive impairment.⁴

FAQs

What is a seizure?

A seizure is abnormal electrical activity in your brain. It brings about a change in awareness and muscle control. It also causes symptoms that affect your behaviour and senses.

Why is LGS called a syndrome?¹

Lennox-Gastaut syndrome is a collection of multiple types of seizures, which includes: 

• Tonic seizures (stiffening of the body, upward eye gaze, dilated pupils, and altered breathing patterns)
• Atypical absences (staring spells)
• Atonic seizures (brief loss of muscle tone leading to abrupt falls)
• Myoclonic seizures (sudden muscle jerks)
• Generalised tonic-clonic seizures (stiffness of muscle and rhythmic jerking)

What are the causes of its occurrence?¹

The following are conditions that can cause LGS: 

• Brain malformations
• Tuberous sclerosis
• Perinatal asphyxia
• Severe head injury

• Brain infections
• Inherited genetic conditions
• Inherited degenerative or metabolic conditions 

How do you manage a patient of LGS?^1,4

Medications along with the other treatment methods, help a lot in seizure control. 

Other treatment options include:

• Dietary therapy with the ketogenic diet
• Vagus nerve stimulation
• Epilepsy surgery (typically a corpus callosotomy, which involves severing the band of nerve fibres that connect the two halves of the brain to prevent seizures from spreading)

In order to manage various comorbidities of LGS, comprehensive multidisciplinary management comprising healthcare professionals of varied specialities is required to ensure that individual patients’ medical, educational, psychological, and social needs are attended to as long as they live. A transition from paediatric to adult care is quite challenging as the provision of care becomes scattered and there are generally fewer resources available for adults compared with children. Patients and their families should receive appropriate educational and psychosocial support to ensure a smooth transition.

Does the disease run in the family?⁷

There is a possibility for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. This is called inheritance. Family health history is crucial to figure out if any other member of the family was ever affected, and it is very important information for your medical team to be aware of.

What are the other associated comorbidities of LGS?⁷

• Mobility restriction/disability
• Sleep disturbances
• Cardiac abnormalities

What should you look out for in LGS patients?³

Patients with LGS have high chances of risk of death. This is for several reasons: 

• Sudden Unexpected Death in Epilepsy (SUDEP): This is a major concern in LGS. What exactly causes SUDEP is yet to be discovered. It may be related to post-seizure heart and breathing issues, and those with frequent convulsive seizures are at a greater risk of death 

• Infection: Reduced mobility can lead to infection, such as pneumonia
• Accidental injury: Atonic or tonic seizures may cause falling and subsequent injury to the patient 

What investigations help in diagnosing LGS?²

• Complete blood count
•  Magnetic resonance imaging brain
• Electroencephalogram
• Genotyping

Summary

LGS is difficult to treat in 30 to 35 per cent of individuals who do not show any cause of occurrence. The outcome of treatment in Lennox-Gastaut syndrome patients varies. With no cure for the disorder, complete recovery, including freedom from seizures, is not possible. Several pharmacological and surgical treatments have been suggested for managing Lennox-Gastaut syndrome, with more options anticipated in the near future to address drug resistance and reduce the risk of lifelong dependency for patients.^{1 2}
Psychoeducation (e.g., cognitive behavioural therapy or mood management) and community support may help patients and their family/caregivers in coping and adapting to the distress of severe behavioural comorbidities of LGS. Therefore, in addition to the medical management of seizures, comprehensive assessment and careful management of comorbidities should be a core aspect of care.⁴