Photo-Dependent Reflex Seizures: Comparison
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Please note this is a comparison between Version 2 by Peter Tang and Version 1 by Dariusz Wojciech Mazurkiewicz.

Reflex seizures (RS) are a group of epilepsies in which seizures are triggered by a specific stimulus. Children and adolescents are the largest at-risk group for the appearance of reflex seizures or epilepsy syndromes with a photoparoxysmal response.

  • photic stimulation
  • seizures
  • electroencephalography

1. Introduction

Reflex seizures (RS) are a group of epilepsies in which seizures are triggered by a specific stimulus. Some patients report that seizures are sometimes or exclusively caused by general internal factors (such as stress, fatigue, fever, sleep, and menstrual cycle) and external factors (such as excess alcohol, heat, bathing, eating, reading, and flashing lights) [1].
It has been known for over a century that flickering light can trigger seizures in susceptible patients [2]. A lot of information has been obtained about the mechanism of intermittent photic stimulation (IPS) and its role in the symptomatology of seizures in children and adolescents. As a result, IPS has become an almost routine procedure in performing diagnostic electroencephalogram (EEG) recordings with stroboscopic light flashes from 2 to 60 Hz to diagnose epilepsy, or the genetic feature, and to evaluate (non)pharmacological treatment [3,4][3][4]. Photoparoxysmal response (PPR) may be responsible for the occurrence of a provoked seizure [1,5,6,7][1][5][6][7].
During childhood and adolescence, the period when epilepsy most frequently begins (about 75% of cases), the PPR to intermittent light stimulation is most pronounced in EEG [8,9,10,11][8][9][10][11]. Therefore, children and adolescents constitute the most numerous at-risk group for the occurrence of reflex seizures or epilepsy syndromes with PPR. An actual number of people in the so-called risk of reflex seizures group is unknown. To date, there is no controlled epidemiological data on the frequency of this type of seizure [12]. It is assumed that amongst the 1% of people suffering from epilepsy, 6.5% have reflex seizures. Within the group of reflex epilepsy, light-induced seizures are the most frequently recorded, accounting for 5% of all 6.5% of reflex seizures [13]. The estimated prevalence of suspected epilepsy among Europeans is 5–10%, while in some genetically determined idiopathic epilepsy syndromes (i.e., juvenile myoclonic epilepsy) this number may rise to 90% [14]. This group includes juvenile myoclonic epilepsy (JME), Dravet syndrome, Eyelid myoclonia, and PhS occipital lobe epilepsy. Patients in this group usually require many years of pharmacotherapy, sometimes with unsatisfactory response to treatment. Most of these epilepsies are genetically determined and although PPR is a common trait, their genetic location varies with the type of epilepsy. Mutations in the SCN1A and SCN2A genes have been found in Dravet syndrome. There is considerable gene polymorphism in JME, and the most common location is chromosome 22 EFHC1, GABRA1, GABRD, CACNB4, CASR, Cx-36 in 15q4, GRM4, BRD2 in 6q21 [15,16,17,18][15][16][17][18]. Mutations associated with juvenile absence epilepsy have been found in the CACNA1H gene. Jeavons syndrome shows remarkable genetic heterogeneity, including mutations in the CHD2 and KCNB1 genes being responsible for this type of epilepsy [19]. The genetic significance in PhS epilepsy was determined, in particular, by focusing on the CHD2 gene after finding it to be the only common gene among the few reported in PhS epilepsy with deletions in the chromosome 15q26.1 region [20].
A mentioned above, even though light-induced epileptic seizures have been documented since the mid-nineteenth century, there are still problems with classifying these types of seizures [7]. The literature on these seizures is limited and the multitude of terms used makes it difficult to classify them unequivocally.
Since the adoption of the International Classifications of Epileptic Seizures (ICES, Commission, 1981) and International Classifications Epilepsy and Epileptic Syndromes (ICE, Commission, 1989), interest in classification and terminology related to epilepsy has remained high [21].
The classifications of seizures and epilepsies published by the International League Against Epilepsy (ILAE) in 1981 and 1989, respectively, were intended to increase the precision of the classification and consider newly identified syndromes and their etiology. The 1989 ILAE classification included both specific electroclinical syndromes and broad syndromes based on seizure types and etiology. It was then proposed to distinguish a group of reflex epilepsy, which, in 2001, was included in the syndromes of reflex epilepsy [22,23][22][23]. It allowed for the distinguishment of a group of patients exposed to seizures provoked by external stimuli. Reflex epilepsies had been divided into two groups. The first group included those caused by simple sensory stimulation—auditory and visual somatosensory stimulation. The second group are those induced by complex stimulation such as: reading epilepsy, musical epilepsy, eating epilepsy, thinking epilepsy [3,24][3][24]. Kasteleijn, in 2001, proposed a terminology and classification of clinical and neurophysiological phenomena relating to visual sensitivity. It aims to standardize the use of clinical terms and definitions. This proposal is divided into four main areas: Clinical manifestations of visual sensitivity, Classification of EEG responses to IPS, Classification of electroclinical phenomena, and Classification of syndromes [25].
ILAE 2017 classification modified the division of epilepsies and classified them into three levels, first by seizure type (focal, generalized or unknown), then by type of onset (focal, generalized, or unknown), and then by specific epilepsy syndromes [26,27][26][27]. Although the etiology is considered at every stage, broadly defined epilepsy syndromes are not considered. Inappropriate diagnosis of isolation reflex seizures can be a problem in the diagnosis and prognosis of this group of patients. Since epilepsy with PPR affects a large group of patients, it is worth distinguishing these groups of patients in order to properly qualify them for long-term anti-epileptic treatment.
The latest ILAE 2022 classification updated diagnostic criteria for epilepsy syndromes of different ages of onset are presented. These criteria are in line with the currently accepted classifications of epilepsy and seizures, and knowledge from advances in genetics, electroencephalography and imaging is being used. Some reflex epilepsy and PPR epilepsy are distinguished [28].
Due to the multitude of terms and definitions used in the literature, it seems important to focus on photo-dependent reflex seizures and carry out their proper differentiation [14].

2. Photo-Dependent Reflex Seizures—Proposal of Classification

Stimulation with a photic signal (TV, pattern, VG, self-inducted) or elimination of central vision (FOS, scotosensitivity) induced PDRS in patients aged 5–18 susceptible to light stimuli. PDRS was classified into the following categories: light-induced seizures and light-deprived seizures. Patients with epilepsy and PPR can have generalized and focal seizures [42,46,47][29][30][31]. Although generalized seizures, such as myoclonic, tonic-clonic, and absence, are the most common, PPR has also been found in patients with occipital epilepsy and temporal lobe epilepsy [47][31]. According to the study by Yang Lu (2008), PPR was observed in 20% of patients with focal seizures [48][32]. Focal seizures are recorded as visual, motor, and sensory disturbances. In photogenic epilepsy, both types of seizures can occur in the same patient. IPS is the leading symptom in photogenic epilepsy. This group includes the so-called pure reflex epilepsy, in which the seizures are caused by different types of light—IPS, patterns, computer games—or by a lack of light. When a seizure trigger is identified, the patient usually avoids the situations or factors that provoke the seizure. Radovici first described eyelid myoclonia and absence seizures in response to eyelid closure while looking at bright lights [49][33]. The occurrence of seizures is related to the phenomenon of autophotostimulation [38][34]. Patients feel positive emotions and relaxation during the seizure, thus leading to self-induced seizures [50,51][35][36]. Since patients provoke a seizure by stereotypical hand movements, this epilepsy can be confused with tics. Patients stare at a light source and wave abducted fingers in front of their faces while slowly closing their eyes or perform other behaviors that create a similar flicker effect. This constellation of symptoms has been termed “Sunflower Syndrome” due to the sun-seeking behaviors of the patients and the characteristic way in which they bend their faces up toward the sun [36][37]. Some patients have seizures that are sensitive to certain patterns. The most common are patterned clothes (grids, stripes), window blinds, escalators, and ceiling tiles [35][38]. Although most pattern-sensitive patients are also PhS, pattern sensitivity may occur in isolation. Pattern-provoked epileptic activity arises in the visual cortex. However, it has been noted that the topography of EEG activity in response to patterns is usually mainly located over the posterior temporal and parietal scalp electrodes rather than the occipital electrodes [12]. In the 20th century, with the development of electronic media and the increasing spread of TV, it was noticed that some people experience epileptic seizures while watching TV. The first study of epilepsy and PhS patients (n = 454) was by Jeavons and Harding in 1975 [52][39]. It found that 35% of patients had seizures only while watching TV, without spontaneous seizures [10]. In 1979, based on the conducted research, Wilkins et al. found that the percentage of PhS patients affected by television increased dramatically when the viewing distance was reduced. Screen size matters [30][40]. A television with a small screen, stimulates a smaller area of the retina than that with a large screen. The results of the study indicated that this increase in sensitivity is due to two factors; firstly, an increase in the amount of stimulated retina and secondly, an increasing resolution of the lines that make up the image. Etemadifar et al., in a TV epilepsy study, found that girls suffered more than boys. In this study, 43.3% of the patients had co-epileptic syndromes, all of them with generalized idiopathic epilepsy, and 56.7% of the patients had pure TV epilepsy [32][41]. In December 1997, after a four-second animation of a blue-and-red Pokémon was broadcast in Japan, 687 people from all over the country, mostly children, were hospitalized due to seizures [31][42]. For 76%, it was the first seizure in their lives. During the Olympics Games in London in 2012, the organizers had to change the TV logo of the event due to the appearance of epileptic seizures in viewers. In some patients, seizures due to hypersensitivity to flashing lights occurred only while playing computer games. Epilepsy associated with playing video games (VG) has been recognized since the early 1980s, with the first definitions being “Space Invader epilepsy”, “Dark Warrior epilepsy”, and “Nintendo epilepsy”. VG is a combination of visual stimuli (screen flickering, program color, patterns and brightness, and the impact of the screen scanning) and other factors such a practice and mental activity. The frequency of seizures provoked by the current widespread nature of video games is not precisely defined. This disease most often affects people aged 9–19 years, more often boys, who spend a significant part of their free time playing computer games. Seizures due to video games have been reported in patients with PhS and non-photosensitive epilepsy. Patterns including epileptiform activity with a maximum concentration over the posterior temporal and parietal scalp, rather than the occipital region as is typical in IPS have been shown [53][43]. It is, therefore, likely that VGs containing multiple patterned images will trigger a different type of seizure when closely examined. Some games are more provocative than others depending on the brightness levels and combinations of colors and blinking lights. According to a study by Kasteleijn-Nolst et al., Super Mario World triggered the first seizure in many patients and proved to be more epileptogenic than standard TV shows and as provocative as shows with flashing lights and patterns [5,34][5][44]. Seven articles present seizures provoked by lack of light or lack of fixation of eyesight. There are two types of stimulation—fixation-off and scotosensitivity [39,40,41,42,43,44,45][29][45][46][47][48][49][50]. Although the majority of people with visually provoked seizures and vision sensitive epilepsy are PhS, pattern-sensitive, or both, there have been a few reported patients with seizures that occur when their eyes are closed, or their focal point vision deteriorates. The term fixation sensitivity (FOS) was originally used by Panayiotopoulos for epilepsy, or EEG abnormalities, or both, caused by a lack of central vision and fixation [54][51]. FOS can occur in both nonphotosensitive and PhS patients and can be in mild and medically intractable epilepsies, as well as in patients without obvious epileptic seizures [39][45]. Another type of stimulation is scotosensitivity, which is defined as epileptic discharges induced in pure darkness. This is a very rare type of epilepsy. Three articles on this topic were found, each one describing individual patients. PhS epilepsy, scotosensitive epilepsy and FOS are often revealed in a resting EEG. Therefore, it is important to distinguish between eye-closure and eye-closed EEG abnormalities due to their different properties and their different responses to intermittent light, darkness and fixation. Eye-closure induces mainly generalized seizure activity that occurs within 2–4 s after closing the eyes, usually lasting 1–4 s [42][29]. In the assessment of general characteristics of the patients, such as sex and age, the researchers have no observed important differences in answer for IPS, but the researchers would like to emphasize that males are more sensitive to VG while females are more sensitivity for TV induced. It may be connected to the higher frequency VG use by males than females.

3. Conclusions

PDRS are the most common of this type of disorder among reflex seizures. Since there are many seizure provoking factors in the world around us, it is important to distinguish amongst them in order to be able to protect the patient exposed to this factor. Photostimulation should always be performed during routine EEG testing, even if the patient does not report any symptoms. The purpose of PS is to identify patients with PPR and determine the appropriate treatment to avoid photostimulation or, if necessary, introduce early treatment to avoid seizures.

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