Lennox Gastaut Syndrome

Lennox-Gastaut syndrome (LGS) is a childhood epilepsy syndrome that typically develops before the age of five, and often persists into adulthood. LGS affects learning and development. It is estimated to occur in 0.1 - 0.28 people per 1,000, is more common in boys and accounts for up to 4% of all childhood epilepsy. LGS can be difficult to treat.

Causes of LGS

LGS can be caused by a variety of structural or genetic disorders and in about 50% of cases no cause can be identified. Where there is a history of brain injury a birth-related brain injury may be caused by a disruption to the flow of oxygen to the brain whereas other brain trauma may be due to head injury. Other causes of brain injury may be due to infections such as meningitis.

Characteristics

Children with LGS experience several different types of seizures, most commonly:

  • Atonic or drop seizures
  • Tonic seizures with stiffening of limbs in waking and sleep
  • Atypical absence seizures which can be frequent and accompanied by blinking and head nods. The child appears unresponsive or in a daze.
  • Focal seizures may also develop and present in variable ways and may occur in sleep.
  • Tonic clonic seizures which are the stiffening jerking type (convulsive) and may be prolonged leading to status epilepticus which is a medical emergency.
  • Myoclonic seizures are the muscle jerking seizures which are not associated with loss of awareness typically.
  • Children with LGS develop difficulties with learning, delays in reaching developmental milestones and behavioural problems. Some children who had a diagnosis of Infantile Spasms (West Syndrome) may go on to develop LGS.

Prognosis

Children with LGS develop difficulties with learning, delays in reaching developmental milestones and behavioural problems. Some children who had a diagnosis of Infantile Spasms (West Syndrome) may go on to develop LGS. Most children with LGS continue to have seizures into adulthood. However, a few may stop having seizures before reaching their teens.  

Diagnosis

EEG findings can be very helpful in making a diagnosis as it may show abnormal activity in the brain between the seizures called slow spike and wave activity as well as abnormal activity during seizures.

Treatment

The treatment of LGS is challenging due to multiple seizure types. The main options are Anti-Seizure Medications (ASMs), dietary therapy and surgical interventions. Treatment plans may be complex, involving multiple ASMs, but the response is variable between children. Most children remain treatment resistant, and side effects can be a major consequence especially where multiple ASMs are used and at high doses. The focus is optimising cognitive functioning and quality of life while reducing seizures to the greatest extent possible.

Anti-Seizure Medications

Sodium Valproate is commonly prescribed as a first line drug. If it is ineffective, then other ASMs may be introduced.

  • Lamotrigine is often used with valproate, combined early in treatment.
  • Rufinimide has been shown to be effective as an add-on drug. Side effects are mild-moderate (appetite reduced, worsening of autism) although a transient seizure increase was observed in some.
  • Topiramate can be effective as an adjunctive therapy for LGS drop attacks. Some behaviour issues have been noted and it is also associated with cognitive problems.
  • Clobazam can be effective in LGS but tolerance can develop and there can be a range of cognitive and behaviour issues.
  • There has also been some positive data on Levetiracetam and Zonisamide in LGS. Perampanel has been shown to reduce seizures in some LGS patients, while increasing seizures in others.
  • Felbamate is approved for restricted use where other options have not worked but only in some countries as it’s use is limited due to side effects.
  • Carbamazepine can increase absences and myoclonic seizures.
  • Since being licenced for use with Lennox Gastaut Syndrome and approved for reimbursement in Ireland Cannabidiol (Epidyolex) is now a treatment option also when combined with clobazam and has been shown to be effective with some cases of LGS. 

Steroids

Steroids can sometimes help atypical absences, drop attacks and non-convulsive status epilepticus but relapse is common. Prolonged use is related to side-effects, so they are only suitable for short term use.

Ketogenic Diet

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet. There are several variations such as the classical MCT oil diet, low glycaemic index diet and the modified Atkins diet. It is a non-pharmacological treatment and is used in combination with ASM’s. The diet has been effective in reducing seizures in LGS and is regarded as safe with side effects being transient and less likely to lead to cognition difficulties and drowsiness.

Surgery

Recent studies of resective surgery on individuals with LGS show promising results, with a high percentage of patients having improved seizure control. It may be used to treat patients with LGS with suspected focal epileptic pathology.

  • Corpus callosotomy is a surgical approach where the white matter between the hemispheres of the brain is severed. This aims to control drop seizures by preventing the spread of epileptic activity across to the other side of the brain. Recent advances have greatly diminished complications of this surgery.
  • Vagus Nerve Stimulation (VNS) – VNS involves the implantation of a pacemaker-like device which sends stimulation along the vagus nerve to the brain to prevent seizures. It has shown to be effective in some people with LGS. It doesn’t interact with ASM’s and side effects are reversible. The procedure is also less invasive than brain surgery.

Overall, while treatments have evolved for LGS in recent years, effectiveness of any one treatment remains very individual. ASM’s have limited success, while access to other treatments like surgery, VNS and the ketogenic diet depends on HSE resourcing and timely access to HSE services.

Further Information