Introduction

Did you know that very young children can experience serious epileptic seizures for which limited medications are available? Lennox-Gastaut Syndrome (LGS) is a type of epilepsy seen in children that includes difficult-to-treat seizures and interferes with proper brain function and development.¹

LGS usually begins in early childhood before age 8, often between the ages of 3 and 5.² It was found to be present in approximately 14-28 per 100,000 people.³ Since LGS can have detrimental long-term consequences through persistent seizures and its effects on mental function, the early and accurate treatment of children with LGS is crucial.³ One of the medications that can be used is the anti-seizure drug rufinamide, which is approved to be used alongside standard medications for therapy against LGS in children. 

Here, the main facts about Lennox-Gastaut Syndrome are clearly explained, and what is known about rufinamide as an adjunctive therapy for children with LGS is described. By the end of this article, you will be educated on how rufinamide works, how it is beneficial for children with LGS and how it can be used in practice so that families and caregivers with children experiencing LGS can have a guideline for this type of medication.

Overview

LGS was first identified by Gastaut in 1966 as a serious form of childhood epilepsy that was difficult to treat.⁴ The common features of LGS as seen in children include a combination of multiple seizure types, learning difficulties, complications during brain development and impairments to proper brain function.² Along with this, LGS has characteristic signs on an electroencephalogram (EEG), showing abnormal brainwaves with slow and sharp wave patterns between seizures and sudden bursts of fast electrical activity during sleep.²

Current treatments for LGS in children?

The treatment of LGS in children mainly aims to reduce the frequency of seizures, particularly the ‘drop attacks’, which are sudden and dangerous falls leading to the risk of causing physical injury.² The treatment consists of a combination of different anti-seizure medications, along with dietary therapy such as the ketogenic diet. In rare cases, surgery, such as Vagus Nerve stimulation and Corpus callosotomy, can be performed.²

Current approved anti-seizure medications include:³

• Felbamate
• Lamotrigine
• Topiramate
• Clobazam
• Fenfluramine
• Cannabidiol
• Rufinamide

Standard therapies for LGS in children

The limitation with the current treatments is that they can be ineffective in reducing the frequency of seizures in children due to their resistance to the medications. They can also have side effects such as tiredness, altered behaviour and adverse reactions.² Furthermore, not every child is suitable for surgery. Along with this, due to the risk of developing disability from a long-term experience of seizures and injuries, it is necessary to develop effective treatments for children with LGS.² 

The management of LGS requires a careful approach, and can show changes across different children. As of now, multiple primary treatments exist, but they can have little effect in decreasing the seizures of some children with LGS.² This highlights the requirement for adjunctive therapies. Adjunctive therapy is a secondary treatment used in combination with the initial treatment or medication to increase the overall efficacy of the treatment.⁵

Rufinamide and its use for LGS in children

What is rufinamide?

Rufinamide was approved in 2008 and is currently used as an anti-seizure drug as an adjunctive therapy for children with LGS, where standard medications are ineffective in reducing the seizures.⁶

How does rufinamide work?

Rufinamide works by regulating the activity of sodium channels in neurons, keeping them in an inactive state to limit the over-excitation (hyperexcitability) of neurons.⁷ During seizures, neurons have excessive activation and consistent firing of action potentials, so blocking sodium channels from becoming activated is a method to keep neurons from being hyperexcited.⁷ 

Effects of rufinamide on LGS symptoms in children?

A clinical study in Japan evaluated the efficacy and safety of administering rufinamide to children with LGS in combination with other antiepileptic drugs over a period of 12 weeks.⁶ The children tested in the study had multiple seizure types, including drop attacks. It was discovered that the administration of rufinamide as an adjuvant therapy led to a 32.9% reduction in the frequency of total seizures.⁶ Importantly, a 24.2% reduction in the frequency of tonic-atonic seizures, meaning that rufinamide was effective for various types of seizures associated with LGS, especially drop attack seizures.⁶ 

Similarly, another clinical study looked at the efficacy and safety of rufinamide in children and adults younger than 20 years of age who were diagnosed with LGS and did not respond to the current anti-epileptic drugs.⁸ They found that 7.8% of all tested individuals became seizure-free and 35.9% had more than half reduction in their seizure frequency upon 16 weeks of rufinamide treatment.⁸ The types of seizures which had the greatest reduction in frequency upon rufinamide treatment were convulsive seizures and drop attacks.⁸ 

This suggests that rufinamide can effectively reduce the frequency of dangerous seizures in children living with LGS. It was also suggested that rufinamide was generally safe and well-tolerated by children.^6,7,8

Side effects of rufinamide in children?

Rufinamide had some side effects that were mostly mild to moderate.

Some common side effects are:

• Tiredness/drowsiness
• Nausea/vomiting
• Loss of appetite
• Increases in seizure frequency ^6,8

Rare side effects include:

• Feeling like having the flu
• Sore throat and stuffy nose (nasopharyngitis)
• Problems with balance and coordination (ataxia)
• Double vision (diplopia)
• Changes in the heart’s rhythm (longer QT interval)
• Severe allergic reaction that can cause skin rashes and fever
• Serious skin condition (Stevens-Johnson syndrome)⁷

When to use rufinamide?

Rufinamide can be used as an adjuvant therapy in children who are 4 years and older with LGS, and with seizures that continue with the same frequency even after the administration of current anti-seizure medications.⁹

How is rufinamide given to children?

Rufinamide can be given to children as an oral suspension.⁷ The administration is twice a day; dosing starts at 10 mg/kg/day, and the dose can be increased every other day in 10 mg/kg increments until 45 mg/kg/day is reached.⁷ It is advised that the drug is taken along with food, as this improves its absorption in the body.⁷

Crucial information for families and caregivers

• Rufinamide does not cure LGS in children, as it is a drug that helps control its symptoms
• Rufinamide treatment begins with a low dose and is increased gradually based on the body weight of the child
• Suddenly stopping rufinamide medication can worsen seizures and lead to status epilepticus
• Benefits may take a few weeks to show once a stable dose is reached¹⁰

FAQs

When should rufinamide be used?

Rufinamide is often chosen when other seizure treatments don't work well. If a child keeps having drop attacks and multiple kinds of seizures although they are on seizure medications, doctors might think of giving rufinamide as an extra treatment.

Can rufinamide take the place of other anti-seizure meds?

Since rufinamide is given as extra therapy, it is used with, not in place of, other treatments.

Is rufinamide safe to use for a long time in children?

The current research shows that rufinamide is mostly safe and easy to handle. In rare cases where serious side effects might happen, it is important that doctors watch them closely. 

Can rufinamide improve the quality of life of children with LGS?

Yes, rufinamide has the potential to improve the quality of life by reducing the frequency of seizures, avoiding injuries and improving their attention and mood.

Summary

Lennox-Gastaut Syndrome (LGS) is a severe type of epilepsy that mainly starts in young children around the ages of 3 to 5. Children with LGS have many kinds of seizures and can also face mental and developmental issues.

Rufinamide is a drug meant to help control these seizures and is used with other medications. Studies show it can cut down on how often seizures happen, mainly the types that make a person fall suddenly or get very stiff. Rufinamide is mostly safe to use. Some children may feel very tired, nauseous or sleepy. In a few cases, it led to allergies, skin issues, or changes in how the heart beats. 

Rufinamide is an effective treatment to be used as an adjuvant therapy in children who do not respond to current medications and have persistent seizures. Therefore, rufinamide can be effective in improving the quality of life of children suffering from LGS. This adjunctive nature of rufinamide must be clear to the families and the caregivers of the children using rufinamide.