Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy syndrome. It is characterized by multiple and concurrent seizure types including tonic seizure, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG), which are very abnormal. Typically, it presents in children aged 3–5 years and most of the time persists into adulthood with slight changes in the electroclinical phenotype . It has been associated with perinatal injuries, congenital infections, brain malformations, brain tumors, genetic disorders such as tuberous sclerosis and numerous gene mutations. Sometimes LGS is observed after infantile epileptic spasm syndrome (formerly called West syndrome). The prognosis for LGS is marked by a 5% mortality in childhood and persistent seizures into adulthood (at least 90% of adults with LGS still have seizures).
LGS was named for neurologists William G. Lennox (Boston, US) and Henri Gastaut (Marseille, France), who independently described the condition. The international LGS Awareness Day is on November 1.
Signs and symptoms
The symptoms vary and progress with age and are characterized by a triad of seizures including tonic seizure, cognitive dysfunction, and EEG findings. The triad may not fully emerge until 1–2 years after first seizure episode.
Seizures
The peak age of onset of seizures is in the first year of life and the seizures evolve into LGS typically between 3 and 5 years of age. The mainstay symptoms are seizures that are frequent – occurring daily and difficult to treat with anti-seizure medications. An estimated 30% of patients with infantile epileptic spasm syndrome (formerly called West syndrome) have been reported to progress with LGS.
Tonic seizures are the most common and present in nearly everyone with LGS. They occur most frequently during non-REM sleep (90% of the time). They initially last for a minute or less and are activated by sleep. The presentation can be subtle. They present often as tonic eyelid opening with some changes in breathing coupled with pupillary dilation, urinary incontinence, increased heart rate, and flushing.
Nonconvulsive status epilepticus occurs in about 50% of patients with LGS. The seizures can cause sudden falling often leading to injury. These "drop attacks" are typically the first manifestation of LGS. The attacks are characterized by a single, generalized myoclonic jerk that precedes tonic contraction of axial muscles.
EEG findings
Findings that strongly suggest LGS include abnormal, consistent slow spike-wave (< 3 hertz [Hz]) on awake EEG. The complexes typically consist of a spike (duration < 70 milliseconds) or a sharp wave (70–200 milliseconds), followed first by a positive deep trough, then a negative wave (350–400 milliseconds). Not every wave is preceded by a spike. Bursts increase and decrease without clear onset and offset. Slow spike waves may occur during seizures or between seizures, or may occur in absence of any observable clinical changes. This helps distinguish LGS from the pattern of extended 3-Hz spike-wave discharges.
Causes
The LGS disease pathophysiology is mostly unknown, but some evidence implicates cortical hyperexcitability occurring at critical periods of brain development.
A lot is know about what causes early life seizures and everyone with LGS has it secondary to a seizure etiology. There are two types of LGS etiologies: idiopathic and secondary. The cause of the idiopathic subtype is unknown. The cause of the secondary subtype occurs when an identifiable underlying pathology is responsible and you can see this pathology on an MRI scan. The most common type of LGS (70–78%) is secondary. These patients tend to have a worse prognosis than those with idiopathic LGS. In up to one-third of cases no cause for seizures can be found.
Brain injury
Seizures that then evolve into LGS most often occur secondary to brain damage. The brain damage can occur from perinatal insults, encephalitis, meningitis, tumor, and brain malformation.
Genetic mutations
Other identified causes of early life seizures include genetic disorders such as tuberous sclerosis and inherited deficiency of methylene tetrahydrofolate reductase. Some of these cases once thought to be of unknown cause may have definitive etiology by modern genetic testing.