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Generalised epilepsies

This chapter is centred on focal epilepsies, in part because less is known about the
pathophysiology of the primary generalised epilepsies, with the exception of absence
epilepsy, which will be outlined briefly here. It is the one class of generalised epilepsy where
there is a plausible model of basic mechanisms. It differs from localisation-related epilepsy
in many important respects. In particular it arises from the thalamocortical system, depending
on the properties of both cortex and thalamus. Until recently there was a consensus on the
mechanisms for the classic 3 per second spike-wave activity, which depended on
synchronisation of the thalamus by rhythmic activity of networks of inhibitory neurons. The
rhythm was thought to arise from the interaction of inhibitory post-synaptic potentials (IPSPs)
with transient low-threshold (T) calcium channels in thalamic cells. Recent evidence,
especially from one of the better models of this condition, the Generalised Absence Epilepsy
Rats from Strasbourg model (GAERS), suggests that the thalamic T current may not be
critical. Work on this model also suggests that the frontal cortex may play a key role in
initiating absence seizures, a point that contributes to blurring the distinction between
localisation-related and primary generalised epilepsies.

Conclusions

The basic neurophysiological mechanisms of some forms of epileptic activity now are
understood in considerable detail. However many important issues remain, in particular on
the basic mechanisms of prolonged seizures and the precise combinations of cellular
pathophysiologies and pathologies in chronic foci. Identifying specific cellular mechanisms
playing crucial roles here should provide useful leads for novel and selective treatments.

Further reading

CRUNELL V, LERESCHE N (2002) Childhood absence epilepsy: Genes, channels, neurons and networks. Nat Rev
Neurosci 3, 371-382.
JEFFERYS JGR (2007) Epilepsy in vitro: electrophysiology and computer modeling. In: Epilepsy: A Comprehensive
Textbook (Eds JJ Engel and TA Pedley), Chapter 38. Lippincott Williams & Wilkins, Philadelphia.
JEFFERYS JGR, JIRUSKA P (2011) Basic mechanisms of seizure generation. In: Epilepsy: The Intersection of
Neurosciences, Mathematics, and Engineering (Eds I Osorio, H Zaveri, MG Frei and S Arthurs). Taylor and Francis,
London.
JEFFERYS JGR (2010) Advances in understanding basic mechanisms of epilepsy and seizures. Seizure 19, 638-646.
JEFFERYS JGR, MENENDEZ DE LA PRIDA L, WENDLING F, BRAGIN A, AVOLI M, TIMOFEEV I, DA SILVA
FHL (2012) Mechanisms of physiological and epileptic HFO generation. Prog Neurobiol 98, 250-264.
JIRUSKA P, FINNERTY GT, POWELL AD, LOFTI N, CMEJLA R, JEFFERYS JGR (2010) High-frequency network
activity in a model of non-lesional temporal lobe epilepsy. Brain 133, 1380-1390.
MORMANN F, JEFFERYS JGR (2013) Neuronal firing in human epileptic cortex: the ins and outs of synchrony during
seizures. Epilepsy Currents 13, 1-3.
SCHEVON CA, WEISS SA, MCKHANN G et al (2012) Evidence of an inhibitory restraint of seizure activity in humans.
Nat Commun 3, 1060.