In up to one-third of cases no cause can be found. Brain injury
Lennox–Gastaut most often occurs secondary to brain damage. The brain damage can occur from perinatal insults, encephalitis, meningitis, tumor, and brain malformation. Genetic mutations
Other identified disorders 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.Progress in genome and exome sequencing is revealing that some individuals diagnosed with Lennox-Gastaut Syndrome have de novo mutations in a variety of genes, including CHD2, GABRB3, ALG13 and SCN2A. The Epi4K study consortium (2013) observed de novo mutations in at least 15% of a study cohort of 165 patients with LGS and infantile spasms using whole exome sequencing. A 2013 study found a high frequency of rare copy-number variation (CNVs) in adult patients with LGS or LGS-like epilepsy.Mutations in the IQSEC2 gene have been associated with this syndrome. This gene is located on the short arm of the X chromosome (Xp11.22). Diagnosis
The diagnosis of LGS should be suspected in children less than 8 years old with seizures of multiple types that cannot be treated with antiseizure medications. Because of high risk of irreversible brain damage in early stages of syndrome (particularly in infants and young children), early diagnosis is essential.
They present often as tonic eyelid opening with some changes in breathing coupled with pupillary dilation, urinary incontinence, increased heart rate, and flushing can occur.Nonconvulsive status epilepticus occurs in about 50% of patients. 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 monoclonic jerk that precedes tonic contraction of axial muscles. EEG findings
Findings that strongly suggest LGS include 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 seizure or between seizures, or may occur in absence of any observable clinical changes which helps distinguish pattern from extended 3-Hz spike-wave discharges. Ocular abnormality
Ocular abnormalities affect around 90% of children. They can present as refractive error, strabismus, cortical visual impairment, and premature retinopathy. Causes
The disease pathophysiology is mostly unknown, but some evidence implicates cortical hyperexcitability occurring at critical periods of brain development.There are two types of LGS: idiopathic and secondary. The cause of the idiopathic subtype is unknown. Secondary LGS occurs when an identifiable underlying pathology is responsible. The most common type of LGS (70–78%) is secondary. These patients tend to have a worse prognosis than those with idiopathic LGS.