Background: The benign character of absence epilepsy compared to other genetic generalized epilepsy
syndromes has often hampered the search for new treatment options. Absence epilepsy is most often treated with
ethosuximide or valproic acid. However, both drugs are not always well tolerated or fail, and seizure freedom for
a larger proportion of patients remains to be achieved. The availability of genuine animal models of epilepsy does
allow to search for new treatment options not only for absence epilepsy per se but also for other genetic - previously
called idiopathic - forms of epilepsy. The recent discovery of a highly excitable cortical zone in these models
is considered as a new therapeutic target area.
Methods: Here, we provide an overview regarding the search for new therapeutical options as has been investigated
in the genetic rodent models (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis
can be achieved, various types of electrical and optogenetical invasive stimulations, different types of noninvasive
stimulation and finally whether absence seizures can be predicted and prevented.
Results: Many factors determine either the cortical and or thalamic excitability or the interaction between cortex
and thalamus and offer new possibilities for new anti-absence drugs, among others metabotropic glutamatergic
positive and negative allosteric modulators. The inhibition of epileptogenesis by various drugs with its widespread
consequences seems feasible, although its mechanisms remain obscure and seems different from the antiabsence
action. Surgical intervention on the cortical zone initiating seizures, either with radiosurgery using synchrotron-
generated microbeams, or ablation techniques might reduce spike-and-wave discharges in the rodent
models. High frequency electrical subcortical or cortical stimulation might be a good way to abort ongoing spikeand-
wave discharges. In addition, possibilities for prevention with real-time EEG analyses in combination with
electrical stimulation could also be a way to fully control these seizures.
Conclusion: Although it is obvious that some of these treatment possibilities will not be used for absence epilepsy
and/or need to be further developed, all can be considered as proof of principle and provide clear directives
for further developments.
Keywords: Genetic absence models, genetic generalized epilepsy, medication, new treatment options, electrical stimulation, transcranial
stimulation, radiosurgery, WAG/Rij rats, GAERS, seizure prediction, seizure prevention, antiepileptogenesis.
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