Lennox-Gastaut Syndrome (LGS)
Lennox-Gastaut Syndrome is a severe developmental and epileptic encephalopathy of childhood. The ILAE classifies it as a distinct syndrome defined by a triad of key features: multiple seizure types, a characteristic EEG pattern, and cognitive impairment. Unlike self-limited epilepsies, LGS is a chronic condition that is notoriously difficult to manage and typically persists into adulthood.
Presentation and Clinical Features
Age of Onset: LGS typically begins in the preschool years, between the ages of 2 and 8 years.
Seizure Profile: The core feature is the presence of multiple seizure types.
Tonic Seizures: These are the most common and defining seizure type. They are sudden stiffening seizures that can affect the entire body, often occurring during sleep and causing injuries from falls if they happen when the child is awake.
Atonic Seizures: Also known as drop attacks, these are brief, sudden losses of muscle tone leading to an abrupt fall. They can be very dangerous and often require the use of protective helmets.
Atypical Absence Seizures: These are prolonged periods of unresponsiveness and staring, often lasting for 10-30 seconds, and are less responsive to treatment than typical absence seizures.
Other Seizures: Myoclonic and focal seizures are also common.
Developmental Trajectory: LGS is an epileptic encephalopathy, meaning the epileptic activity itself leads to cognitive and developmental decline. Children with LGS often have pre-existing developmental delays, but their condition worsens after the onset of seizures. They typically have moderate to severe intellectual disability and significant behavioural difficulties.
Etiology: LGS is usually symptomatic, meaning it is caused by an underlying brain disorder. It can be the evolution of an earlier epileptic encephalopathy like Ohtahara Syndrome or West Syndrome (infantile spasms), or it can be due to a brain malformation, genetic disorder, or a history of brain injury.
Investigations
Diagnosis: The diagnosis is based on the clinical triad of multiple seizure types, cognitive impairment, and specific EEG findings.
EEG: The EEG is the most crucial diagnostic test. It shows two characteristic patterns:
Interictal (between seizures): Diffuse slow spike-and-wave discharges (2–2.5 Hz).
During Sleep: Bursts of fast (10–20 Hz) discharges are often seen, particularly during sleep.
Neuroimaging: An MRI of the brain is essential to identify any underlying structural brain abnormalities.
Genetic/Metabolic Testing: Genetic and metabolic investigations are crucial to determine the aetiology, which may have implications for management.
Management and Prognosis
Treatment: LGS is one of the most treatment-resistant epilepsy syndromes. Management requires a multifaceted approach, often involving polytherapy (multiple medications) and non-pharmacological interventions.
First-Line Medications: Valproate and Clobazam are commonly used as first-line agents.
Other Medications: According to international guidelines, other effective medications include Lamotrigine, Rufinamide, Levetiracetam, and Topiramate. Cannabidiol (CBD) is a more recent addition to the treatment arsenal, especially for drop attacks.
Medications to Avoid: Carbamazepine and oxcarbazepine can worsen seizures and should be avoided.
Non-Pharmacological Therapies:
Ketogenic Diet: This high-fat, low-carbohydrate diet is a highly effective treatment for LGS, particularly for drop attacks, and should be considered early in the treatment course for drug-resistant cases.
Corpus Callosotomy: This surgical procedure, which involves cutting the nerve fibres that connect the two hemispheres of the brain, is a palliative option considered for refractory drop attacks.
Vagus Nerve Stimulation (VNS): A VNS device can be implanted to help reduce seizure frequency.
Prognosis: The prognosis for LGS is generally poor. Seizures often persist into adulthood, and individuals have significant lifelong cognitive and motor disabilities.
Supportive Care: A multidisciplinary team including neurologists, therapists, and educators is essential for managing the complex needs of individuals with LGS and providing support for their families.