Experimental treatment options in absence epilepsy

Contains fulltext : 182124.pdf (preprint version ) (Open Access)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 perse 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 non-invasive 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 anti-absence 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 spike-and-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

Spike-wave discharges and sleep spindles in rats

Contains fulltext : 28623.pdf (publisher's version ) (Open Access

Search for new targets of deep brain stimulation for epilepsy treatment [Review article]

Contains fulltext : 157203.pdf (publisher's version ) (Open Access)Although clinical trials in refractory epilepsy are currently carried out, the field of deep brain stimulation (DBS) in epilepsy is still at its initial stage. Little is known about where, when and how to stimulate and what would be the short and long consequences. Animal studies might provide clinicians with new ideas regarding targets for DBS. Here an overview is given regarding old and new targets in rodent models of temporal lobe epilepsy. The evidence from animal models showed that stimulation of the subiculum – either in responsive or scheduled manner - is anticonvulsant in different seizure and epilepsy models, indicating that the subiculum might be a promising candidate for DBS targets. For the rest, the antiepileptic effects of low frequency stimulation were established mostly in kindling models. The presence of a critical time window in which stimulation was effective following after discharges on kindling acquisition, demonstrates that timing of DBS is an important factor for the anticonvulsant effects of DBS.11 p

Evolution of anterior and posterior sleep spindles in rats

Contains fulltext : 54745.pdf (publisher's version ) (Open Access

Een nieuw anti-absence medicijn?

Contains fulltext : 179104.pdf (publisher's version ) (Open Access)Op 8 juni 2016 verdedigde Valerio D'Amore zijn proefschrift 'The role of group I metabotropic glutamate receptors in absence epilepsy' aan de Radboud Universiteit, Nijmegen1. D'Amore onderzocht de rol van metabotrope glutamaatreceptoren in cortex en thalamus van WAG/Rij-ratten, een genetisch absence-epilepsiemodel, met als doel om aan te tonen dat antagonisten van deze stoffen ontwikkeld kunnen worden als geneesmiddel tegen absence-epilepsie.3 p

Translationeel absence-epilepsie onderzoek

Contains fulltext : 179648.pdf (publisher's version ) (Open Access)4 p

Thalamic and cortical correlates of sleep spindles in rats

Contains fulltext : 55318.pdf (publisher's version ) (Open Access

Phasic events in normal and epileptic rats: time of day effects

Contains fulltext : 55610.pdf (publisher's version ) (Open Access

Effects of remacemide and its metabolite FPL 12495 on spike-wave discharges, electroencephalogram and behaviour in rats with absence epilepsy

Contains fulltext : 28626.pdf (publisher's version ) (Open Access)The effects of the anti-convulsant drug remacemide and one of its active metabolites FPL 12495 were examined in a genetic model for generalized absence epilepsy, the WAG/Rij strain of rats. Number, mean and total duration of spike-wave discharges were measured following oral administration of remacemide and FPL 12495, together with parameters of background electroencephalographic activity (EEG) and spontaneous behaviour in the recording cage. A decrease in the number of the spike-wave discharges was found after remacemide administration. At the highest dose there was near total suppression of the spike-wave discharges. There were no important effects on behaviour and on spectral content of the background EEG, suggesting that remacemide has little side effects. A decrease in the number of spike-wave discharges was also found after FPL 12495 gavage and there was a prolongation of the mean duration. Behavioural changes were only noticed after the highest dose. These were accompanied by changes in the spectral content and particularly by an increase in the amplitude of the delta and the high beta frequencies, together with a decrease in the spindle frequency range. FPL 12495 appeared to be more potent that remacemide in all its effects. The effects of mainly FPL 12495 are uncommon in the sense that so far no other investigated drug shows a decrease in the number together with an increase in the mean duration of the discharges. It seems that in contrast to other anti-epileptic drugs, FPL 12495 exerts a differential action on the two commonly distinguished mechanisms controlling number and duration