FOS is a phenomenon elicited by conditions that eliminate central vision in both natural situations, for example, with closed eyes or in complete darkness, and the experimental setting (Panayiotopoulos, 1998). It usually occurs in children with an idiopathic epileptic syndrome, whereas reports in children with cryptogenic and symptomatic epilepsies are rare (Koutroumanidis et al., 2009). Given its high degree of reproducibility, this phenomenon offers, from a pathophysiologic point of view, an intriguing and unique opportunity to study epileptic activity. The mechanisms underlying FOS are not yet fully understood. Ever since the first reports (Panayiotopoulos, 1998), FOS has been considered to be related to alpha rhythm generators, its appearance depending on variables that normally modulate the alpha rhythm. Over time, the FOS pattern has acquired an important role both in clinical practice, by providing clues to recognize specific epileptic conditions (especially in infancy) (Panayiotopoulos, 2000), and in the neurophysiologic setting, by enhancing knowledge of cortical occipital hyperexcitability (Strigaro et al., 2011). An ongoing, intriguing historical debate is on the distances and/or points of contact between FOS and the other forms of occipital hyperexcitability such as PPR. Although the borders between these two conditions are not clearly defined (in rare contexts they may even coexist), the main neurophysiologic differences, and in particular the opposite effects induced by IPS (Gumnit et al., 1965), may be due to the involvement of different visual pathways, that is, the magnocellular system in PPR and the parvocellular system in FOS (Wilkins, 1995). The FOS pattern has more recently been studied by means of various advanced techniques, which have provided new insights into the underlying network, excitability mediators, and metabolic changes of this phenomenon. Of interest, during the eyes-closed condition, recent EEG/functional MRI (fMRI) studies have revealed blood oxygen level–dependent (BOLD) predominant activations in the peristriate areas (Iannetti et al., 2002; Di Bonaventura et al., 2005), whereas MRS has documented a dynamic increase in the glutamate concentration in the same regions (Peca et al., 2010), thereby confirming the occipital hyperexcitability. Lastly, studies based on transcranial magnetic stimulation have recently confirmed an alteration in cortical excitability that is probably due to an imbalance between γ-aminobutyric acid (GABA) and glutamate transmission (Strigaro et al., 2011). Because this peculiar phenomenon is rarely observed in adult patients with epilepsy (Kurth et al., 2001), in this article we decided to focus on its occurrence in adult life in order to better define syndromes associated with it and to try to identify the possible relationship between the FOS pattern and specific etiologies. In accordance with data in the literature (Panayiotopoulos, 1998), in our population the typical FOS pattern, whether bilateral or unilateral, was predominant in the posterior regions (especially the temporooccipital, occipital, temporal, temporoparietal regions), and was rarely associated with generalized discharges, it often being an expression of secondary bilateral synchrony. In 10 of the 15 patients, we had the opportunity to document some ictal events (simple partial with predominant visual symptoms, complex partial, and secondary generalized), all of which arose from the posterior regions. These data are of considerable interest, since seizures in adult life have rarely been reported (Ferlazzo et al., 2010). All the seizures were recorded in patients with drug-resistant epilepsy, which accounted for a large proportion of our cohort (11 of 15). The most curious finding to emerge from our study was the prevalence of symptomatic epileptic syndromes (11/15). Indeed, according to published data, FOS is typically a pattern observed in children with idiopathic epileptic syndromes, with rare reports of symptomatic cases (Koutroumanidis et al., 2009; Hassan et al., 2011). The prevalence of symptomatic syndromes in our population suggests that the persistence of the FOS phenomenon in adulthood might be related to specific etiologic factors. The most frequent cause of FOS in the group of patients with symptomatic epileptic syndromes was malformation of cortical development (MCD) (especially band heterotopia). Another interesting finding was the association of this pattern with celiac disease, the typical neurological complication of which is posterior epilepsy, which is usually related to occipital calcifications. Such calcifications were, however, observed only in one of our three cases. Because other anecdotal reports (Licchetta et al., 2011) have also documented the association of FOS phenomenon and celiac disease in the absence of occipital calcifications, we believe that the diagnostic process in patients with “cryptogenic” posterior epilepsy and a FOS pattern should include an accurate screening for celiac disease. In three of our adult patients affected by an idiopathic epileptic syndrome (Gastaut syndrome), the FOS pattern is likely to represent a “continuation” of the same phenomenon started in childhood.
The present study was limited by a number of factors, including its retrospective design and a selection bias. With regard to the selection bias, we identified a significant number of symptomatic drug-resistant epilepsies, owing to the fact that the patients enrolled were selected in a tertiary epilepsy center. In contrast to what is expected in idiopathic forms, in which both seizures and the FOS phenomenon usually gradually disappear, a symptomatic etiology and drug resistance may explain the persistence of this rare EEG phenomenon in adult life. Consequently, we cannot rule out that patients with persisting FOS associated with idiopathic forms of epilepsy, or other cryptogenic forms, in which the seizures were controlled, escaped us. This explanation, however, remains speculative, since the data available on the long-term evolution of idiopathic epilepsies with FOS phenomenon are currently still somewhat limited.
In conclusion, the data that emerge from this retrospective study highlight certain crucial points. The revision of the electroclinical findings and syndromic characteristics in our population suggests that the FOS phenomenon may be observed in adult life, and that when it does, unlike the childhood form, it often represents the EEG expression of symptomatic epilepsies. FOS may, in some conditions, point to specific etiologies underlying the epileptic process, the most noteworthy being MCD (such as double cortex) and celiac disease. In this regard, the FOS EEG pattern may be considered an important practical clue that should be taken into account in clinical investigations.