Introduction

Lennox-Gastaut (Len-ox gas-toh) Syndrome is an uncommon but significant type of epilepsy that generally starts during the early stages of a person’s life - usually between the ages of 3 to 5, with boys being targeted more than girls in most cases. It is a rare type of epilepsy, affecting only around 1-10% of childhood epilepsy cases and can be identified by different kinds of drug-resistant seizures.¹ The seizures experienced can prove difficult to control and have a big effect on the quality of life and adaptive behaviours of the person. Resultant electroencephalogram (EEG) tests often indicate delays in brain activity over time and thus in turn, also problems with development. As Lennox-Gastaut Syndrome continues into later life, most individuals will require dedicated help with basic daily activities, preventing them from being able to live independently.

If someone has drug-resistant epilepsy, this means at least two different anti-seizure medications have been given to them but they still experience seizures. Different people are given different medications based on the types of seizures they experience and the tolerance levels they have. Lennox-Gastaut Syndrome (LGS) is very difficult to medicate since it is highly resistant to a lot of anti-epileptic drugs and can require multiple medications, which also increases the risk of side effects. Some medications given that treat other types of seizure can in fact make LGS seizures worse.

Deep Brain Stimulation (DBS) is a procedure that is being researched and used that puts electrodes into different areas of the brain. A pulse generator is inserted in the body and the electrodes are joined to it, sending electrical signals to the brain to reduce symptoms. DBS treatment is at the moment being used in the management of various neurological conditions and movement disorders such as Parkinson’s, dystonia, epilepsy. By sending electrical impulses in a predetermined cycle, it can help bring down the frequency of seizures or even prevent them in cases.

Causes of Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut Syndrome does not develop from a single cause. However since it can occur from various different reasons, it can be categorised as either secondary or idiopathic LSG.² Secondary (symptomatic) LSG is the more common type, affecting around 75% of the cases. This is caused by a known underlying issue, such as an infection in the brain, malformations and also brain tumours.³

Idiopathic or cryptogenic LGS however has no identifiable cause but recent studies have suggested that a significant number of the children studied may possibly have underlying genetic disorders or mutations that can contribute.⁴

Seizures can be classified into different categories:  myoclonic, tonic, atonic and atypical absence seizures. These can all occur at the same time but affect the person differently. Tonic and atonic seizures both happen suddenly and change muscle tone but the difference lays in the fact that tonic seizures cause the muscle to suddenly become stiff, while atonic seizures make the muscle become limp.⁵ An atypical absence seizure has a slow-acting long-duration effect, often accompanied with other types of seizures. Myoclonic seizures are categorised by a very brief twitching or jerking of the muscle group, which generally don’t cause a loss in consciousness, but it can be quite strong and still do damage to the body.⁶

Most seizures experienced by individuals are symptomatic i.e. happening due to issues before or around the time of birth, such as infections during pregnancy or problems occurring with the flow of blood to the brain. There are also some cryptogenic seizures, which would mean that they occur due an unknown reason.⁷

Deep Brain Stimulation (DBS)

Deep Brain Stimulation is an exceptional process that has been used to provide relief to many cases of neurological conditions, such as individuals with essential tremor and Parkinson’s disease. It works by placing high-frequency electrodes in different sections of the brain which are then joined to a neurotransmitter. By stimulating them, it is possible to regulate abnormal brain activity and reduce tremors.⁸ The important matter to consider is that a process of trial and error is required for each subject as individuals have different symptoms and frequencies which when combined with resistance with anti-epileptic drugs, can make treatment difficult. One trial conducted in animals has shown that a high-frequency stimulation of the anterior nucleus of the thalamus can lead to a decrease in the occurrence of seizures, while a low-frequency of the same area can actually initiate a seizure.⁹

One of the main locations that the electrodes can be inserted in is the anterior nucleus of the thalamus (ANT). These nuclei play an important role in the function of alertness in the body and also in memory, but they have been shown to also support the occurrence of seizures. In a trial carried out with the ANT being stimulated, DBS produced a big drop in the frequency of seizures. This was shown and displayed on an electroencephalogram (EEG), a chart which shows and measures brain activity.¹⁰ The majority of candidates did not suffer any major side effects, with some mentioning pain during implantation and a very small percentage experiencing migraines and nausea.

Another important location that can be targeted is the centromedian nucleus of the thalamus. This is located in the back region of the thalamus and its role is in attention in the body, especially controlling the activity in the outermost layer of the brain, which is crucial for intensive cognitive tasks. A trial performed in 2006 showed that in a group of 13 people with LGS, there was an overall reduction of 80% in seizures experienced. However, more tests with a bigger clinical trial size are needed to be able to justify that the CMT has a huge effect on the frequency of seizures in LGS.¹¹

Importance of DBS in Lennox-Gastaut Syndrome

Deep Brain Stimulation can be used when normal anti-epileptic medication stops having an effect on controlling or even preventing seizures. These included drugs such as lamotrigine, sodium valproate, rufinamide, topiramate and clobazam. Although they can help to a certain extent, they are not a long-term treatment and with the various changes in the frequency and form of seizures normally experienced, constant changes will need to be made to the dosage given.¹² Being able to send electrical impulses instantly to stimulate areas of the brain is also a much more instant relief compared to the delay that medication can have, which is crucial in seizures that are rapid and jerky. This is essential in seizures that cause loss of consciousness, which also leads to bodily harm if the individual is standing and has a sudden drop.

There needs to be a lot of planning to be carried out before the actual procedure to make sure that the adverse effects are dealt with so there is less pain. A study on LGS individuals showed that 20.9% had pain at the implant location. Alongside that, 22.7% of them had a numb feeling and 12.7% of them encountered implant infection.¹³ With the majority of cases of LGS occurring during childhood, extra care needs to be given to ensure that the adverse effects are kept to a minimum as the body, especially the brain, is still developing.

Neurostimulation has the added benefit of not only being flexible in terms of adaptability, but also being able to reverse the effects by under stimulating the brain. This would help provide the optimal frequency of electrical impulses, which is not possible with anti-epileptic medication.

Summary

DBS offers a positive therapeutic pathway for people suffering from drug-resistant DBS, with a lot of clinical trials showing drops in the frequency of seizures. However, the clinical trials performed were mostly on small populations and oftentimes non-randomised, meaning that the patients were manually assigned to a treatment group. In order to unlock the full potential of this treatment, randomised controlled trials will need to be take place on a large control group in order to determine the efficacy of DBS and also how safe it is in individuals.¹⁴

Deep Brain Stimulation is still in the early stages, with more lab research required in order to find the optimal implantation location, understand the mechanisms involved and identify the best candidates who will benefit the most from this treatment. Further studies on larger populations will help understand the process better and be able to hopefully have better control over seizures, especially in those suffering from drug-resistant Lennox-Gastaut Syndrome where regular medication is no longer effective in managing their epileptic attacks.

In its current stage, DBS has the potential to be a useful treatment option for managing seizures, but more research has to be done to make sure that the procedure is successful, long-lasting and as non-intrusive as possible to limit the adverse effects.