Epilepsy is usually referred to as plural epilepsy because there are different parameters that define different epileptic syndromes. These criteria are the type of seizure, the cause of the seizure, symptoms and abnormalities of the electroencephalogram (electrical activity produced by the brain).
The causes of an epileptic seizure are multiple, we distinguish symptomatic epilepsies from idiopathic epilepsies.
Biological mechanisms of epilepsy
A seizure is an abnormally prolonged electrical activity of a set of neurons in the cerebral cortex. The action potential or nerve influx is an electrical message created by an inversion of positive and negative charges on either side of the neuron membrane, resulting from an ion exchange between the cell and its environment (Fig B). At rest, the positive charges are outside the neuron (Fig A)
Under normal conditions, the role of each neuron is to receive, process, and transmit the electrical message to other neurons via the synapse via neurotransmitters (green spheres on the scheme).
The neuron that transmitted the electrical signal then enters a repolarization phase, i.e. a reversal of charges between the outside and the inside of the neuron, during which it is inactive (FigC).
In the case of an epileptic seizure, the neurons become hyperexcitable, that is, a single stimulation leads not to an action potential but to a succession, a train of repetitive action potentials without a rest period (FigD).
This neuronal hyperexcitability is explained in idiopathic epilepsies by mutations in ion channels, located on the neuron membrane, which allow ion exchange and thus depolarization and repolarization. In general, the membrane becomes too permeable to return to a resting potential.
Hyperexcitable neurons form the epileptic focus. Focal epileptic seizures, which originate in a highly delimited region of the brain, are distinguished from generalized seizures resulting from a train of action potentials that extends throughout the brain.
Hyperexcitability is very often accompanied during seizures by hypersynchrony, with several groups of neurons simultaneously generating action potential trains at the same time and at the same rate, amplifying the intensity of symptoms.
At Paris Brain Institute
The “Cellular Excitability and Dynamics of Neural Networks” team, co-led by Stéphane CHARPIER, Vincent NAVARRO & Mario CHAVEZ, aims to understand how the brain becomes epileptic (epileptogenesis), how it produces seizures, and to identify the relationships between the abnormal electrical activity of a single neuron and the clinical signs observed in patients.
Microelectrode implantation in the brain during intracerebral EEG exploration of patients with treatment-resistant epilepsy is a new approach that allows tracking of brain activity at the scale of a few neurons, during seizures, but also at a distance (inter-critical period), and shortly before seizures (pre-critical period). The acquisition of this information takes place in the Epilepsy Unit, with the help of the CENIR-STIM platform of Paris Brain Institute, and the data is transferred directly to Paris Brain Institute servers, where it is analysed by Professor Vincent Navarro’s team. It is thus possible to follow the activity of groups of neurons continuously for days: Paris Brain Institute is the only institute in France with such a registration procedure.
The brain consumes much of our daily energy intake. Synapses in particular, which connect neurons to each other, consume a lot of energy. Every time neurons communicate with each other, a lot of energy is consumed. Not surprisingly, not having enough energy to maintain neural communication has deleterious effects.
The goal of Jaime de Juan-Sanz’s team is to understand and identify the essential molecular mechanisms involved in maintaining synapse bioenergetics under normal conditions and to show a relationship between energy dysfunction and seizure.
