LENNOX-GASTAUT SYNDROME

Introduction

Lennox-Gastaut (LGS) is an uncommon pediatric epilepsy syndrome that makes up around 10% of childhood epilepsy. Lennox-Gastaut is characterized by the onset of multiple different seizure types, severe cognitive delay, and a distinct EEG pattern.

History

Lennox-Gastaut is named after the two physicians who first documented the disease. In the 1950’s, Dr. William Lennox described a particular EEG finding that would match an epilepsy syndrome that Dr. Henri Gastaut was studying in the mid 1960’s. Dr. Henri Gastaut described a childhood epilepsy with frequent tonic and absence seizures. Later it was found that both Dr. Lennox and Dr. Gastaut were studying the same epilepsy syndrome and thus it was coined Lennox-Gastaut syndrome.

Symptoms

Lennox-Gastaut is frequently associated with intractable epilepsy, severe cognitive impairment, and characteristic EEG.

Epilepsy

Patients with Lennox-Gastaut tend to present with multiple seizure types.

• Tonic
• Tonic-Clonic
• Atonic (Drop attacks)
• Myoclonic
• Atypical Absence (With characteristic EEG pattern)

Seizures in patients with Lennox-Gastaut are frequent in nature and tend to cluster making them at high risk for evolving into Non-convulsive status epilepticus (NCSE) with some studies showing an incidence of NCSE being over 50%.

The average of seizure onset in patients with LGS is between 3-5 years of age. Almost all patients with an LGS diagnosis have an onset of seizures before 8 years of age.

Cognitive Impairment

Cognitive impairment before seizure onset is seen in roughly 40% of patients. Depending on the severity of the disease there may be a delayed onset of cognitive delay after the patient has their first seizure.

Characteristic EEG pattern

EEG in patients with LGS can be complex and difficult to read. Due to the multitude of seizure types, LGS seizure can present in several different ways which may make it difficult to differentiate the disease from others. However, in LGS there is a very characteristic EEG pattern known as atypical absence which helps to set it apart from others.

Atypical absence seizures are defined as slow (1.5-2.5 Hz) irregular polyspike and wave activity. It is important to note that atypical absence seizures differ from typical absence seizures in that they are slower (Typical absence seizures tend to be in the 3-5 Hz range) and are often asymmetric (Typical absence seizures are almost always generalized). Atypical absence seizures are NOT triggered by hyperventilation.

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UPMC “Lennox-Gastaut Syndrome”
Figure 2.1 showing Atypical Absence seizure with characteristic 1.5-2.5 Hz slow waves with asymmetrical polyspike discharges.

Other patterns that can be seen in Ictal EEG of an LGS patient include:

• Rhythmic, high amplitude discharges in the high alpha-beta ranges seen in tonic seizures.
• Arrhythmic bursts of polyspike-wave discharges seen in myoclonic seizures.

Classifications of disease

LGS diagnoses typically fall into the following two categories: Secondary & Idiopathic

Secondary LGS:

This accounts for about 75% of all cases and describes a known primary cause. Any damage to the brain before or during birth can be considered a primary cause to LGS. These include:

• Infection
• Frontal lobe injury
• Tuberous Sclerosis
• Perinatal asphyxia
• Perinatal stroke
• Abnormal development

Idiopathic LGS

These account for the other 25% of LGS cases and have no known cause.

Linkage between Lennox-Gastaut & West Syndrome

An LGS diagnosis has been to known to frequently follow a myriad of other childhood epilepsy diagnoses. None are more common than the diagnosis of West Syndrome. Up to 30% of known LGS cases follow a diagnosis of West Syndrome despite no known cause for the linkage of the two.

Treatments & Prognosis

Long-term prognosis is generally unfavorable for patients with LGS. While mortality secondary to LGS is low sitting around ~3 %, severe cognitive impairment and treatment resistant epilepsy still persists in the majority of patients. Patients with a history of West Syndrome also tend to have worse outcomes than those with idiopathic LGS.

Treatment options in LGS vary due to the multitude of seizure types. Antiepileptic drugs (AEDs) tend to be the mainline treatment for LGS but rarely does a single AED give complete relief of seizures. Valproic Acid and Lamotrigine are the most commonly used AEDs in LGS. Other forms of treatment include the Ketogenic Diet, VNS, and surgical intervention. LGS patients are good candidates for corpus callostomy to help reduce the frequency of seizures, though it is rare for surgical intervention to be completely curative.