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).

Pathophysiology

Fig. 1: Thalamocortical circuitry involved in the pathogenesis of absence seizures. Thalamic relay (TR) neurons exhibit spike-wave discharges that result from activation of T-type Ca++ channels, followed by hyperpolarization mediated by GABA released from thalamic reticular (NRT) neuronsThe pathogenesis of absence seizures involves the cortico-thalamic-cortical circuit (Onat FY et al., 2013). Glutamatergic neurons from cortical layer VI send activation signals down to the thalamus' nucleus reticularis Excitatory thalamic relay neurons connect to cortical pyramidal neurons and produce rhythmic oscillatory neuronal firing between these two regions of the brain 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 Inhibitory GABA-ergic projections from thalamic nucleus reticularis neurons connect with other neurons and thalamic relay neurons, but not with the cortex.

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. Other medications which can worsen absence seizures are sodium channel blockers like Carbamazepine, phenytoin and gabapentin.

References

Onat FY, van Luijtelaar G, Nehlig A, Snead OC (2013) The involvement of limbic structures in typical and atypical absence epilepsy. Epilepsy Res 103 (2-3):111-23. DOI: 10.1016/j.eplepsyres.2012.08.008 PMID: 22989853.d