Dr. John Swan, director of the Cain Foundation Labs and co-director of Neurological Research Institute (NRI) describes how NRI/Texas Children's physician-scientists discover and clinically translate cutting-edge treatments for childhood epilepsies.
What is Lennox-Gastaut syndrome?
Lennox-Gastaut syndrome (LGS) is a form of severe childhood epilepsy that firsts manifests in children between the ages of 2 to 5 years and often persists into adulthood. Children with this syndrome have life-long behavioral, psychological and cognitive problems. There is also an increased risk of death due to uncontrolled seizures and/ injuries from sudden drop attacks.
Early infantile epileptic encephalopathies (EIEE) are a group of severe seizure disorders that occur in early childhood. Epilepsy of infancy with migrating focal seizures (EIMFS, also previously known as migrating partial seizures of infancy) is one of these.
Childhood epileptic encephalopathies (EEs) comprise a group of seizure disorders that manifest early in life and are commonly associated with abnormalities in cognitive, sensory and motor skills. There are various causes of childhood EEs. Injury to the brain during development of the fetus or at birth is a common cause. Thanks to recent advances in exome sequencing technology, it is increasingly evident that many rare EEs are a result of sporadic mutations in individual genes.
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Early infantile epileptic encephalopathies (EIEEs) are a heterogenous group of seizure disorders that begin in infancy. Some of them are present at birth whereas others arise later in infancy. In the recent years, advances in gene sequencing techniques have identified numerous genetic mutations that are thought to be responsible for many of the EIEEs.
It is known that the human brain has its own rhythmic activity. Some of these brain rhythms are relatively slow - occurring only a few times per second while others are faster and occur 30 to 80 times every second. However, with recent advances in electronic instrumentation it is now very clear that the brain produces even faster rhythms. Some of these rhythms are perfectly normal like “ripples” that occur 80-200 times per second. Others are even faster but most of these high frequency oscillations (HFOs), which sometimes occur 600 times per second, are thought to be abnormal.
Normal neuronal activity depends on the fine equilibrium between the actions of excitatory neurotransmitters (eg: glutamate) and inhibitory neurotransmitters (eg: gamma-aminobutyric acid, GABA). Usually, GABA, the major inhibitory neurotransmitter, counterbalances neuronal excitation in the brain, preventing neuronal hyperexcitabilty and seizures. At the same time, in order to ensure that neuronal activity continues at the optimal level, it is critical that GABA present in the space between neurons does not accumulate or linger.
Dravet syndrome is a rare and catastrophic form of incurable epilepsy that begins in infancy. Initially, these children develop normally but by the second year of life, they exhibit a progressive decline. It starts initially as febrile seizures i.e. seizures triggered by high fever but eventually progresses to severe spontaneous seizures. Over time, these children commonly exhibit developmental delays in cognitive and sensory abilities, and autistic traits. Moreover, the incidence of SUDEP (sudden unexplained death in epilepsy) is high among these patients.