Understanding ictogenesis in generalized epilepsies

Abstract

Generalized seizures are defined by bilateral symmetric and synchronous epileptiform EEG discharge over the entire convexity and commonly thought to involve the entire brain homogeneously. The characteristic 3–3.5 Hz Spike-and-Wave pattern is conceived as a resonance phenomenon originating in a cortico-thalamic circuit where it can start at variable sites. Investigations with EEG source analysis, magnetencephalography, positron emission tomography and single photon emission computerized tomography, functional magnetic resonance imaging and transcranial magnetic stimulation have suggested that generalized seizures have cortical onset and the thalamus has an essential role in the recruitment of a network comprising frontal, parietal and occipital cortex and the default mode network. Studies of reflex epileptic traits have shown that ‘generalized’ ictogenesis largely uses pre-existing functional anatomic networks normally serving physiological functions. It has therefore been proposed to consider these epilepsies as system disorders of the brain. Treatment is fundamentally pharmacological with a role for behavioral interventions. Generalized epileptic encephalopathies of early childhood are sometimes surgically remediable.

Keywords::

• cortico-thalamic network
• default mode network
• epileptic network
• functional imaging
• generalized epilepsy
• ictogenesis
• reflex epilepsy
• source analysis
• system epilepsy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The concept of generalized epilepsy as involving the entire brain (or entire cortex) homogeneously is not valid any longer.

• Generalized seizures are generated in an ictogenic network involving parts of the frontal, parietal and occipital cortex, the default mode network and the thalamus. A variety of triggers feed into this circuit.

• This concept is based upon concurrent findings of advanced neurophysiology, multiple methods of functional imaging and magnetic resonance morphometry.

• On the background of genetically mutated neurons generalized, ictogenesis ‘hijacks’ functional anatomic networks for important physiological functions using them to produce seizures.

• Generalized epilepsies are therefore now understood as system disorders of the brain.