Absence Seizures

Absence seizures are short seizures with behavioural arrest and generalised 3-Hertz spike-and-wave discharges on EEG. Absence seizures occur in multiple genetic generalized epilepsies, including Childhood Absence Epilepsy (CAE), juvenile absence epilepsy (JAE), and Juvenile Myoclonic Epilepsy (JME).

The pathogenesis involves the cortico-thalamic-cortical circuit^[1].The thalamus' nucleus reticularis receives glutamatergic neurons from cortical layer VI. Excitatory thalamic relay neurons connect to cortical pyramidal neurons.Inhibitory GABA-ergic projections from thalamic nucleus reticularis neurons connect with other neurons and thalamic relay neurons, but not with the cortex.

The thalamic nucleus reticularis' neurons can fire rhythmically (for example, to generate sleep spindles) or constantly in single spikes. Spikes in thalamocortical networks and thalamic nucleus reticularis neurons influence these firing patterns.An aberrant oscillatory rhythm can result from T-type channel defects or enhanced GABA-B activity. T-type calcium channels act as low-threshold transient calcium channels. After depolarization, T-type channels momentarily allow calcium in before inactivating. Reactivation requires a protracted GABA-B receptor-facilitated hyperpolarization.

Hence T-type calcium channel suppressors like ethosuximide and valproate are used for treating absence seizures. GABA-A agonists like benzodiazepines that preferentially activate thalamic nucleus reticularis neurons can also decrease absence seizures. However Vigabatrin, which increases GABA-B activity will increase absence seizures.