The Overlap between Headache and Epilepsy in the Light of Recent Advances in Medical Genetics

Abstract

Migraineurs show an higher frequency of epilepsy (range 1–17%) than general population (0.5–1%), and at the same time migraine prevalence among patients affected by epilepsy is also higher (range 8–15%) than that reported in healthy individuals [11-13]. Especially in children this comorbidity is found often [14]. Seizures and migraine attacks share different pathophysiological mechanisms. Both events may be sign of an underlying brain lesion, or have a probably genetic origin. In this respect, it has been shown that in epilepsy occurs hyperexcitation, while in migraine a brief hyperexcitation period (depolarization) is followed by a long hypoexcitation period (spreading depression), followed again by hyperexcitation, as rebound phenomenon. Moreover, it has been shown that a disexcitability (hyper- and hypo-excitation in the same migraineurs at different points in time) underlines both the phenomenon [1]. Cortical Spreading Depression (CSD) is believed to underlie both migraine and epilepsy [15,16], even in patients affected by migraine without aura. CSD is characterized by a slowly propagating wave of sustained strong neuronal depolarization that generates transient intense spike activity as it progresses into the brain tissue, followed by neural suppression which may last for minutes. The phase of depolarization is associated with a regional cerebral blood flow increase, whereas the phase of reduced neural activity is associated with a reduction in blood flow [17]. It is crucial to remark that while an epileptic discharge can birth exclusively in the cortex, the pathophysiology of headache has its origin at multiple cortico-subcortical levels. Thus, the two cascades of events (headache and epilepsy) show independent ways that can crossover only at the cortical level [18,19]. In headache and epilepsy overlap, after the cortical cascade of events, their onset and propagation are triggered when CSD and epileptic focus reach a definite threshold, lower for CSD than for seizure [6,8,20,21]. Moreover, the onset of CSD and that of the epileptic seizure may facilitate each other [22]. Triggering factors may be environmental or individual (genetically determined or not), determining an ions flow and leading to CSD, through neuronal and glial cytoplasmic bridges rather than through