The importance of the family heritage in epilepsy

Epilepsy is a common neurological disorder that affects people of all ages. It is characterized by spontaneous and unpredictable paroxysmal neuronal firing occurrences that can progressively recruit larger brain areas and networks, and which can eventually evolve in clinically evident seizure. Despite enormous research effort, there is little evidence that allows the pathogenesis of epilepsy to be completely clarified as well the turning point from an electrical discharge into a clinically evident attack. Several efforts have recently been given to the prediction of a seizure in order to apply a therapeutic treatment just before it. On the other hand, rather than the prediction of a single seizure, a genetic or familial risk factor of epilepsy is better investigated through the analysis of brain network modulation in order to help the prediction of the possibility of developing epilepsy. An important step in this direction was assessed by Bharath and colleagues [1] who based their work on evidence of genetic influences on the organization of human cortical functional networks [2]. In the mentioned pivotal study [1] on resting state functional magnetic resonance imaging (fMRI), Bharath and colleagues investigated abnormal functional organization in epileptic patient brain networks as correlated with the presence of epilepsy in the relatives of each patient. Brain networks constantly change dynamic state, switching between movement and rest, behavioral and cognitive tasks, wakefulness and sleep. The epileptic brain presents further network features with the transient occurrence of paroxysmal firing within neuronal assemblies, which – time after time end up with a seizure. The characterization of neural networks in epilepsy has become increasingly relevant, because localized forms of epilepsy are related to an abnormal functioning of specific brain networks without structural damage. Seizures and electroencephalography (EEG) spiking are considered the result of an imbalance between inhibitory and excitatory potentials, producing a hyperexcitable state where the physiological inhibition mechanisms are not sufficient to control the abnormal rhythms of neural firing leading to a paroxysmal depolarization shift. The novelty of the mentioned paper [1] is also in the application of modern techniques, such as those based on graph theory, in the study of fMRI. Graphs are mathematical representations of complex systems defined by nodes and links between nodes. Several studies suggested that the human brain can be modeled as a network; in brain networks, nodes could be associated with brain regions, whilst links could be associated with anatomical, effective or functional connections. Structural anatomical connectivity pertains to the anatomical connections between brain regions describing the physical (axonal and dendritic) wiring of the brain; this is the case of studies based on MRI. Functional connectivity refers to statistical dependences between spatially distinct neurophysiological recordings; this is the case of neurological studies based on EEG [3–6] or fMRI, like the mentioned paper that collected both structural and functional data. Effective connectivity denotes the causal influence exerted amongst neural systems as for example with brain stimulation. The application of this theory on epilepsy brought interesting results. For example, in a recent paper on fronto-temporal focal epilepsy [7], the authors demonstrated that resting state network features distinguish the affected and non-affected hemisphere where the epileptic focus was located, and underlined that these effects were more evident in drug-free patients than in those undergoing pharmacological therapy. Regarding familial and genetic influences on brain connectivity, a recent paper on functional coupling [8] demonstrated gender differences in some of the resting state networks. Summarizing, the paper by Bharath et al. [1] stresses the fact that the cortical network features a specific architecture which could predict a sort of epileptic risk factor. Although this study was carried out only on probands with hot water epilepsy, further research could investigate brain connectivity modifications in more common epilepsies to visualize and quantify factors that make people more vulnerable to epilepsy. In the future, it can be expected that connectivity markers will contribute to increased understanding of the pathogenesis of epilepsy. Furthermore, future research