Invited ReviewFixation-off sensitivity
Highlights
► Fixation-off sensitivity (FOS) is characterized by the appearance of epileptiform discharges occurring after eyes-closure and lasting as long as the eyes are closed. ► FOS is induced by elimination of central vision/fixation. ► FOS is probably associated with occipital hyperexcitability but its intrinsic epileptogenic potential seems to be low.
Introduction
Fixation-off sensitivity (FOS) is a phenomenon induced by elimination of central vision/fixation (Panayiotopoulos, 1981). This term refers to a condition that may either manifest clinically with seizures or only represent an EEG abnormality. FOS is characterized by posterior or generalized epileptiform discharges that consistently occur after closing of the eyes and last as long as the eyes are closed (Panayiotopoulos, 1998). FOS may be easily demonstrated using methods that eliminate fixation (e.g. Frenzel lenses) without preventing light from reaching the retina, thus distinguishing FOS from pure scotosensitivity (Panayiotopoulos, 1998).
We review most important studies dealing with the clinical, neurophysiological and pathophysiological aspects of this fascinating but still obscure phenomenon.
Section snippets
Historic background
The term FOS was coined by Panayiotopoulos (1987). This phenomenon was first observed in four children with occipital paroxysms (two of them had Panayiotopoulos syndrome, one had idiopathic childhood occipital epilepsy of Gastaut and one symptomatic occipital epilepsy) (Panayiotopoulos, 1981). Panayiotopoulos was the first to describe the characteristic occurrence of this pattern after eye closure and elimination of central vision/fixation. In those same years also Gastaut (1982) and Newton and
EEG description and diagnostic aspects
FOS is characterized by continuous epileptiform discharges (spikes, spike wave or sharp wave focal, regional or generalized) that consistently occur within 1–3 s of eye closure (although sometimes they may be delayed for a few additional seconds), persist throughout the eye-closed state (i.e., when central vision and fixation are blocked or compromised) and disappear immediately with eye opening (Fig. 1, Fig. 2, Fig. 3). Other means of eliminating central fixation also lead to the reoccurrence
Differential diagnosis
Testing for actual fixation-off is required to differentiate FOS from pure forms of scotosensitivity (Pazzaglia et al., 1970), in which EEG discharges or epileptic seizures are elicited by darkness. Scotosensitive epilepsy is defined as seizures and EEG abnormalities induced by the complete elimination of retinal light stimulation (Panayiotopoulos, 1998). However, patients with pure scotosentivity do not exhibit EEG abnormalities when fixation is hampered by the use of translucent spherical
Related conditions
Overall, FOS is a rare phenomenon. It is most commonly encountered in patients with idiopathic childhood epilepsies with occipital paroxysms (Gastaut type), and Panayiotopoulos syndrome when occipital paroxysms occur (Panayiotopoulos, 1981, Panayiotopoulos, 1998, Panayiotopoulos, 2007), and represents about 0.2% of epilepsies (Koutroumanidis et al., 2009). FOS may also be observed in symptomatic or cryptogenic focal (Panayiotopoulos, 1981, Maher et al., 1995, Kurth et al., 2001, Iannetti et
Epileptogenicity potential
FOS-related seizures have been described as myoclonic (Garcia Silva et al., 1987), absences (Koutroumanidis et al., 2009), and absence status epilepticus (Ming and Kaplan, 1998). However, the overall intrinsic epileptogenic potential of FOS is presumed to be low, and the FOS-related occipital discharges that occur in idiopathic occipital lobe epilepsy and most of the generalized FOS discharges in idiopathic generalized epilepsies do not seem to be associated with overt clinical manifestations (
FOS and photosensitivity
FOS has EEG features that are the opposite of those observed during photosensitivity. Despite the conflicting corresponding mechanisms underlying these two phenomena (Panayiotopoulos, 1998), both FOS and photosensitivity can occur in the same patient, and one phenomenon may evolve into the other (Panayiotopoulos, 1979, Koutroumanidis et al., 2009). Eye-closed discharges of FOS are elicited by darkness, and are inhibited by fixation and central vision. Conversely, eye-closure abnormalities
Pathophysiology
The rarity of FOS prevents large group studies, so that the underlying pathophysiology of this condition remains not fully understood. However, several studies adopting different methodologies have been conducted so far to better investigate the pathogenesis of this intriguing phenomenon.
Conclusion
FOS is an intriguing phenomenon, its uniqueness being represented by the fact that elimination of central vision/fixation is a specific precipitating stimulus that induces epileptiform discharges even in presence of light. Despite the fact that the results of several studies suggested the involvement of occipital hyperexcitability, the exact mechanism underlying FOS remains somewhat obscure. Therefore, further research is required to investigate this condition, and shed light on the
Conflict of interest
None declared.
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Cited by (20)
Epilepsy with eyelid myoclonias (Jeavons syndrome): An electro-clinical study of 40 patients from childhood to adulthood
2021, SeizureCitation Excerpt :We also showed a possible circadian influence on the discharges, with a potential activating effect of the sleep-wake transition [26,34,35] as in other absence epilepsies [36]. It is not always easy to distinguish ECS from FOS, considering that the two phenomena can coexist and may be misinterpreted [13,37]. Eye-closure-related paroxysms are self-limited, of brief duration, and are suppressed by complete darkness.
The clinical significance and electrophysiologic findings of fixation-off and closure of the eyes sensitivity: Data from a prospective unselected population
2021, Epilepsy ResearchCitation Excerpt :This was a very easy method, successfully performed in all patients. Brigo et al. stressed that FOS and scotosensitivity should be made differentiated (Brigo et al., 2013). Scotosensitivity is defined as epileptic discharges elicited in pure darkness.
SYNGAP1 mutations: Clinical, genetic, and pathophysiological features
2019, International Journal of Developmental NeuroscienceFixation-off sensitivity in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome
2019, SeizureCitation Excerpt :posterior or generalized epileptiform discharges that consistently occur after closing of the eyes and last as long as the eyes are closed for more than 3 s [2,3]. It is differentiated from other “eye-condition” related visual sensitive phenomena, including eye closure sensitivity (just immediately triggered by eye closure lasting for 3 s or less) and scotosensitivity (elicited by complete darkness; irrespective of eye opening and closure) [2,3]. Although FOS has been reported in various epileptic conditions representatively including idiopathic childhood occipital epilepsies, it has never been reported in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome so far.
Electroclinical characteristics and syndromic associations of “eye-condition” related visual sensitive epilepsies—A cross-sectional study
2018, SeizureCitation Excerpt :Occipital lobe excitation by decreased level of GABA can induce generalized seizures when the spread is supra-sylvian and focal-onset seizures when the propagation pathway is infra-sylvian [4]. FOS/ECLDS seems to represent the expression of a marked imbalance of cortical excitability towards an enhanced excitatory transmission leading to occipital hyperexcitability, although the precise location or minimum threshold volume of hyperexcitable occipital required to develop FOS remains unknown [7]. Defective glutamatergic and GABAergic pathways are believed to determine occipital cortex hyperexcitability observed in FOS [15,16].