By: Aliana Gordon
It is possible to “outgrow” seizures! It is most commonly occurring in childhood absence epilepsy. One possibility for this is that certain genes may be age-specific (1). It is theorized that as a child grows, genes mature as well. Genes provide hereditary coding for the making of proteins, such as gamma-aminobutyric acid receptor (GABA). For CAE, this protein has been observed to be dysfunctional but luckily there is a good chance of remission with the use of medication. Through a 2014 study, complete remission occurred in 64% of the children participating who took a drug that increased the GABA receptor’s affinity (2). This is a great feat as CAE accounts for approximately 10% of all epilepsies in children fifteen years and younger.
Childhood Absence Epilepsy
As the name suggests, childhood absence epilepsy is the onset of absence seizures typically starting in early childhood. CAE is a primarily generalized seizure type that begins between the ages of four and eight years. The seizures manifest by impaired consciousness, including a stop in movement that can last approximately nine seconds and can occur up to 200 times in a day (3). There has been a tendency for children to outgrow their epilepsy and for the seizures to disappear in adolescence (4).
The Science Behind It
The cessation of seizures in CAE is proposed to be a result of axonal maturation as the child grows. The maturation can lessen or eliminate seizure activity because of the decrease in time delays between neuron signals. Through its active period, the axons in the brain become more myelinated, meaning there is more protection on the axons and increases the speed of neural conduction (3). The speed of the neuron matters to properly integrate the signals throughout the brain, rather than have an overwhelming number of signals resulting in abnormal brain activity relating to seizures (5).
A variety of molecular defects can attribute to the development of childhood absence epilepsy. One of the most researched subjects regarding CAE is the development of the gamma-aminobutyric acid receptor (GABA), which is a receptor protein in the brain that regulates its excitability (6). The GABA receptor is a major inhibitory neurotransmitter that aids in transmitting signals from neuron to neuron by acting as a channel. It facilitates the movement of negatively charged chlorine atoms across the cell membrane. But with mutations in the GABA receptor, can result in dysfunctional receptors that decrease the regulation of signals. This overstimulates the brain with excessive signals producing seizures.
Rats have been used in experimental studies as they have exhibited electroencephalogram (EEG) signatures like CAE. It has been observed that bursts of larger spikes will occur when there is a genetic defect that affects the time constant on inactivation. Using experimental observations for the rat homolog of CAE, a deficiency of GABA and the process of axonal myelination can account for a clinical course.
Treatment
Through studies, the use of medication has been proven helpful to reduce seizures, including benzodiazepines, anticonvulsants, anesthetics, and neurosteroids. These drugs interact with binding sites on the GABA receptors to increase its affinity while maintaining brain regional specificity (6).
One of the studies that have been conducted researched if initial treatment of ethosuximide or valproic acid affected remission in CAE (2). A cohort of 59 children participated in this study who took one of the two drugs. After being followed for a minimum of five years, 38 kids had complete remission. They had eradication of seizures and EEG signatures without any atypical features. Ethosuximide had a greater success rate of with 76% of the children going into remission. This parallels with the experimental studies with rats previously mentioned.
Works Cited
Chen, Yucai et al. “The role of T-type calcium channel genes in absence seizures.” Frontiers in neurology vol. 5 45. 9 May. 2014, doi:10.3389/fneur.2014.00045
Berg, Anne T., et al. “Long-Term Seizure Remission in Childhood Absence Epilepsy: Might Initial Treatment Matter?” Epilepsia, vol. 55, no. 4, Feb. 2014, pp. 551–57, https://doi.org/10.1111/epi.12551.
Liu, Y., Milton, J. & Campbell, S.A. Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability. J Comput Neurosci 46, 197–209 (2019). https://doi.org/10.1007/s10827-019-00711-x
Milton, John, et al. “Outgrowing Neurological Diseases: Microcircuits, Conduction Delay and Childhood Absence Epilepsy.” Computational Neurology and Psychiatry, 2017, pp. 11–47, https://doi.org/10.1007/978-3-319-49959-8_2.
“Childhood Absence Epilepsy: MedlinePlus Genetics.” Medlineplus.gov, 2014, medlineplus.gov/genetics/condition/childhood-absence-epilepsy/.
Smith, T A. “Type A gamma-aminobutyric acid (GABAA) receptor subunits and benzodiazepine binding: significance to clinical syndromes and their treatment.” British journal of biomedical science vol. 58,2 (2001): 111-21.
Guilhoto LM. Absence epilepsy: Continuum of clinical presentation and epigenetics?. Seizure. 2017;44:53-57. doi:10.1016/j.seizure.2016.11.031
