Reflex Seizures

Benjamin G. Zifkin

Renzo Guerrini

Perrine Plouin

Introduction

Reflex seizures are reliably triggered by some identifiable factor.²⁰⁰ Reviews include Beaumanoir et al., Zifkin et al., and Wolf et al.¹¹^,²¹⁰^,²¹³ The identification of a patient with reflex epilepsy depends on the physician’s awareness and on the observations of the patient and witnesses. The epileptogenic trigger must occur often enough in everyday life so that its relation to the resulting seizures can be suspected. If the trigger is ubiquitous, however, the seizures appear to occur by chance or with no obvious antecedent.

The study of reflex seizures has also furthered understanding of cortical organization in man and has implications for our understanding of how and why some apparently generalized seizures may begin.

Definition and History

Seizures induced by light stimulation were known from classical antiquity, and in the 20th century before the electroencephalographic (EEG) era.¹⁶⁶^,¹⁸⁹ The use of the term reflex has been controversial. Hall⁸⁵ first applied it to epilepsy in 1850. Arguing that no reflex arc is involved in reflex epilepsy, others proposed terms such as sensory precipitation⁶⁵^,¹⁵⁶ or stimulus-sensitive epilepsies.⁴² Wieser noted that sensory precipitation epilepsy is a misnomer because some reflex seizures, for example, those triggered by cognition, are not precipitated by sensory stimuli.¹⁹⁷ In the 19th century, Brown-Séquard²⁷ noted that “certain parts of the central nervous system possess an elevated excitability so that any minimal stimulation may cause a crisis.” Both Gowers⁷⁷ and Hughlings Jackson⁹⁵ described reflex seizures triggered by various causes including sudden noise, bright sunlight, movement, and tapping the head, which are still accepted reflex seizure types. In the 20th century, Adrian and Matthews¹ first documented the effect of light on the normal EEG. The stroboscope became available after World War II and rapidly led to further progress as flicker stimulation and its clinical and EEG effects could be easily studied. Important studies by Walter and Walter,¹⁹⁵ and later by groups led by Gastaut in France and by Bickford in America, yielded basic information about those EEG responses to stroboscopic flicker (intermittent photic stimulation [IPS]), which were reliably linked to seizures. Television screens and sunlight are the most common environmental triggers of visual-sensitive seizures; triggering by television broadcasts and video games has become notorious in recent years, leading to increased interest in reflex seizures.

Classification

Some earlier classifications and the publications on which they were based described “simple” and “complex” reflex epilepsies. Binnie¹⁹ noted: “A distinction should be made between seizures evoked by simple, unstructured sensory stimuli and those precipitated by complex cognitive activities, often with an emotional component. The former are interpretable in terms of known physiological events (not strictly reflex processes) following a stimulus, whereas the latter may offer insights into the complex mechanisms underlying cognition.” Wolf and Inoue²⁰⁹ described reading epilepsy and praxis induction as complex reflex epilepsies.

Complex reflex epilepsies are characterized by seizures triggered by relatively elaborate stimuli whose specific pattern is the determining factor in seizure evocation. The attacks are precipitated by stimuli involving integration of higher cortical function, rather than by relatively simple sensory stimuli, and may be evoked by anticipation of the stimulus. Latency from stimulus onset to the clinical seizure or evoked abnormal paroxysmal EEG activity is typically longer than in simple reflex epilepsies, such as photosensitive epilepsy, in which the response to flicker is usually almost immediate. These properties, enunciated in the 1985 proposal for classification of epilepsies,⁴² had been systematically described in the pioneering work of Forster.⁶¹ To avoid confusion, it should also be emphasized that the term complex, as applied to reflex epilepsy, does not refer to a classification of the induced seizures. Although many varieties are not accepted as epileptic syndromes in the current international classification, partly because of the occurrence of spontaneous seizures in the same patients, they are described as “epilepsies characterized by specific modes of seizure precipitation.”⁴³ Despite this, the induction of attacks in these patients is prominent and often quite stereotyped, and the Commission’s 1989 definition of a syndrome—“a cluster of signs and symptoms customarily occurring together”—may be met. In others, for example, with “language-induced seizures,” the clinical pattern may overlap other more clearly defined entities.

The current classification proposal⁵⁵ defines reflex epilepsy syndromes as those “…in which all epileptic seizures are precipitated by sensory stimuli. Reflex seizures that occur in focal and generalized epilepsy syndromes that are also associated with spontaneous seizures are listed as seizure types.” Thus, this proposal also recognizes few reflex epilepsy syndromes:

Idiopathic photosensitive occipital lobe epilepsy
Other visual-sensitive epilepsies
Startle epilepsy
Primary reading epilepsy
Musicogenic epilepsy

Reflex seizures are often classified according to the stimuli that trigger them rather than by the type of seizure that is triggered. The classification proposal also includes, under seizure types, a list of precipitating stimuli for reflex seizures. These stimuli are:

Visual stimuli
Flickering light—color to be specified when possible
Patterns
Other stimuli
Thinking
Praxis
Reading
Somatosensory
Proprioceptive
Eating
Music
Hot water
Startle

It is important to note that reflex seizures are not distinguishable from spontaneous seizures except for the fact that they are triggered in some identifiable way; that is, a reflex generalized tonic–clonic seizure is clinically the same as one that occurs spontaneously.

Basic Mechanisms of Reflex Epilepsy

Animal Models

There are two types of animal model of reflex epilepsy. In the first, diffuse or regional cortical hyperexcitability is induced chemically or by the creation of a lesion. The second model involves naturally occurring reflex epilepsies or seizures induced by specific sensory stimulation in genetically predisposed animals.

The first approach has been used since 1929, when Clementi³⁸ induced convulsions with intermittent photic stimulation after applying strychnine to the canine visual cortex. Strychninization of auditory,³⁹ gustatory,⁴⁰ and olfactory cortex¹⁴⁰ also produced focal irritative lesions that could produce seizures with the appropriate afferent stimulus. EEG studies showed that the clinical seizures (chewing movements), which were induced by photic stimulation in rabbits with strychnine lesions of the visual cortex, resulted from rapid transmission of the epileptic discharge from the visual cortex to masticatory areas.¹⁹⁰ Paroxysmal discharge from visual cortex may also spread to frontorolandic areas during seizures.⁶³^,⁶⁶ The ictal EEG spread was thought to represent corticocortical conduction,³⁸^,⁶³ although later work with pentylenetetrazol also implicated thalamic relays⁶⁶ and demonstrated spread of the visual-evoked potential to the brainstem reticular formation.⁶⁴ Hunter and Ingvar⁹⁶ identified a subcortical pathway involving the thalamus and reticular system and an independent corticocortical system for radiation of visual-evoked responses to the frontal lobe. In cats and monkeys, the frontorolandic region was also shown to receive spreading-evoked paroxysmal activity from auditory and other stimuli.¹⁸^,²⁸

The second approach, the study of naturally occurring or induced reflex seizures in genetically susceptible animals, has been pursued in chickens with photosensitivity,⁴⁵^,¹⁰⁵ rodents susceptible to sound-induced convulsions,³⁵ the E1 mouse sensitive to vestibular stimulation,¹⁷⁹ and the Mongolian gerbil sensitive to a variety of stimuli.¹²⁶^,¹²⁷ Most of these are of limited relevance to human epilepsy but are of interest to the drug industry as rodent models are useful as relatively cheap and standardized methods for testing possible antiepileptic drugs.

The only species in which naturally occurring reflex seizures and EEG findings are similar to those in humans is the baboon Papio papio,¹¹³ but the light-induced epileptic discharges in baboons occur in the frontorolandic area, rather than in the occipital lobe as they do in human photosensitive epilepsy.¹¹² EEG, visual-evoked potentials, intracerebral recording, and lesion and pharmacologic studies show that visual afferents are necessary to trigger frontorolandic light-induced epileptic discharges in these animals. Unlike human photosensitivity in which the occipital cortex is hyperexcitable, in the baboon the occipital lobe does not generate this abnormal activity, but sends corticocortical visual afferents to hyperexcitable frontal cortex, which is responsible for the epileptiform activity.¹³⁷ The interhemispheric synchronization of the light-induced paroxysmal EEG activity and seizures depends mainly on the corpus callosum and not on the brainstem. Brainstem reticular activation depends initially on frontal cortical mechanisms until a seizure is about to begin, at which point the cortex can no longer control reticular activation. The genetically determined hyperexcitability may be related to cortical biochemical abnormalities, involving regulation of extracellular calcium concentration,⁵¹^,¹⁶¹ or an imbalance between excitatory and inhibitory neurotransmitter amino acids¹²⁴ similar to those described in feline generalized penicillin epilepsy and in human epilepsy.⁷⁴

Visual-sensitive Epilepsies and Seizures

Reflex seizures and epilepsies sensitive to visual stimulation, especially flashing light, are the commonest and longest known, and will be described first. Visual sensitivity has been defined as “having seizures evoked by the physical characteristics of a visual stimulus in daily life or by IPS.”¹¹¹ Recognition of seizures induced by flashing light predates the EEG. Before clinical EEG, seizures were reported with environmental flicker or with sudden changes in light intensity. Gastaut et al. reported an early series of patients investigated with stroboscopic IPS during EEG recording.⁶⁸ Historically, photosensitivity has meant an abnormal response to light and since the development of the stroboscope, an abnormal response to flicker stimulation during EEG recording is generally called photosensitivity. This flicker sensitivity is common to different types of seizures induced by visual stimuli, but subtypes in which patients are reproducibly sensitive to more complex visual stimuli can be distinguished among patients, who are almost always sensitive to intermittent photic stimulation at some time. Pure photosensitive epilepsy, in which seizures occur only with environmental light stimulation, is the most common reflex epilepsy. The induction of focal occipital lobe seizures by the same types of visual stimuli is more common than previously thought. Television and sunlight are the most common environmental triggers of visual-sensitive seizures; triggering by television broadcasts and video games has become notorious in recent years. Visual-sensitive epilepsy is included as a reflex epilepsy syndrome in the most recent proposed classification of epilepsy syndromes.⁵⁵

Several types of EEG response to flicker have been described. An epileptiform EEG response to IPS is a photoparoxysmal response (PPR). These may be restricted to the occipital area or be apparently generalized. Different responses may occur in the same patient depending on the stimulator used, the stimulation protocol, age, and medication effects. In untreated subjects, only generalized paroxysmal epileptiform discharges in response to IPS (spikes, polyspikes, and spike-and-wave complexes) are clearly linked to epilepsy: Apart from those with idiopathic photosensitive occipital epilepsy (IPOE), less is known about patients with clinically evident visually triggered seizures but who have only focal occipital PPRs. These responses are most common with stimulation from 10 to 30 flashes per second.

Epidemiology of Visual Sensitivity

Most studies are retrospective and target specific patient groups. Following seizures triggered by the video game Mario World in 1992, Quirk et al.¹⁶³ prospectively studied the
incidence of visually-induced seizures and PPRs in newly diagnosed epilepsy patients in the United Kingdom. For all ages, a conservative estimate was that the incidence of epilepsy with PPRs was 1.1 per 100,000, about 2% of all new cases of epilepsy. Incidence rose to 5.7 per 100,000, or 10% of all new cases, in patients from 7 to 19 years old.

PPRs and clinical photosensitivity show marked age dependency. They are very rare before age 2 years. In Dravet syndrome (severe myoclonic epilepsy of infancy), responses may be abnormal before age 2 but without evident seizures, and Oguni et al.¹⁴⁸ reported a subgroup in whom myoclonic seizures and atypical absences could be triggered by constant illumination, rather than by IPS, depending on the brightness of the light. This sensitivity tended to disappear before age 5 years. Only one case has been reported of an infant aged 15 months who experienced about 20 seizures in 3 weeks when brought into a bathroom with bright white walls and shiny bright chromed plumbing; he showed the following symptoms: Motion arrest, deviation of the head and eyes to the left, jerks of the eyelids, looking afraid, and right occipital seizure on the EEG. He had no further seizures until he was 11, when occipital seizures recurred.¹⁷²

Both PPRs and visually induced seizures show a clear female preponderance of about 60% of cases, and photosensitivity appears to peak at around puberty. Whether photosensitivity declines with age in patients is debated; several report that it declines in the third decade, while others found no decline with age.¹¹¹ PPRs occur in normal subjects, especially in children up to 16 years old, in whom a prevalence of 1.3% has been reported, and this photosensitivity declines with age. Studies in young adult male aircrew candidates in several countries yielded PPR rates of 0.5% to 0.7%.

Genetics of Photoparoxysmal Responses

Genetic studies of photosensitivity have been hampered by differences in stimulation methods and in classification of the EEG responses. The reduction of sensitivity with age, especially in asymptomatic children, also makes transgenerational studies impossible or difficult to interpret. Monozygotic twins have shown almost 100% concordance for PPRs. Waltz and Stephani reported that photosensitivity is significantly more common in 5- to 10-year-old siblings of proband offspring of a photosensitive parent (50%) than in siblings of photosensitive children without parental photosensitivity (14%). The highest risk of seizure (33%) was in photosensitive siblings of a proband with parental photosensitivity, and the lowest (4%) in nonphotosensitive siblings of probands without parental photosensitivity.¹⁹⁶

A single gene for photosensitivity has not yet been identified. Three different loci have been found, one on each of chromosomes 2 (in a single family), 7q32, and 16p13, and the last two in families with prominent myoclonic epilepsy.¹⁵⁸ Photosensitivity occurring in some patients with identifiable epileptic syndromes (e.g., juvenile myoclonic epilepsy [JME]) is inherited separately from the other epileptic disorder.

Clinical Aspects of Visual Sensitivity

The proposed classification recognizes idiopathic photosensitive occipital lobe epilepsy and “other” visual-sensitive epilepsies as reflex epilepsy syndromes, requiring that all seizures be triggered. Other cases are classified as seizure types, which are more common, and it is not specified whether these represent generalized or focal epilepsy.

Pure Photosensitive Epilepsy

Pure photosensitive epilepsy is characterized by seizures exclusively provoked by flicker. These patients do not have spontaneous seizures. Forty percent of patients with seizures and photosensitivity studied by Jeavons and Harding, Binnie et al., and Kasteleijn-Nolst Trenité et al. are reported to fall into this group. In one study, 84% of patients had seizures reported as generalized tonic–clonic, whereas absences occurred in only 6%, partial motor seizures (possibly asymmetric myoclonus in some cases or unrecognized idiopathic photosensitive occipital epilepsy) in 2.5%, and myoclonic seizures in 1.5% of patients.¹⁰⁴ However, these proportions are subject to bias; patients will come to medical attention after a convulsion in front of the television but may have already had many subtle unobserved reflex seizures with brief myoclonic or absence-like events. Patient self-reporting of these triggered seizures can be extremely inaccurate: Over half of known photosensitive epilepsy patients questioned immediately after stimulation denied having had brief but clear-cut seizures induced by IPS and documented by video-EEG monitoring.¹¹⁰ In laboratory studies with video monitoring, most events are myoclonic jerks¹¹⁰ and patients commonly report eye pain and feelings of eyestrain. The developmental and neurologic examinations are normal.

Idiopathic Photosensitive Occipital Epilepsy

IPOE⁸⁴ is recognized as a reflex epilepsy syndrome in the proposed diagnostic scheme. IPOE is a relatively benign, age-related syndrome without spontaneous seizures. Seizures evoked by visual stimuli were formerly thought to be almost exclusively generalized despite the clear occipital localization of visual function, though asymmetric myoclonus could occur. Induction of partial seizures by visual stimulation, including typical complex partial seizures, is now well recognized.⁹² Intermittent photic stimulation can induce clear-cut partial seizures originating in the occipital lobe.⁸¹^,⁹² As in more typical photosensitive subjects, environmental triggers include television and video games. The symptoms may remain localized to the occipital area for several minutes even after the stimulus has ceased: Visual blurring, blindness, or elementary visual hallucinations may occur.⁸¹^,¹⁶⁹^,¹⁸⁸ The clinical seizure pattern depends on the pattern of spread. The initial reflex visual symptoms may be followed by versive movements and motor seizures. Myoclonus is not typical, but migraine-like symptoms of throbbing headache, nausea, and, sometimes, vomiting are common and can lead to delayed or incorrect diagnosis.

Photosensitive Epilepsy with Spontaneous Seizures

The remaining 60% of patients with epilepsy and photosensitivity also have spontaneous seizures, and photosensitivity gives rise to attacks precipitated by environmental visual stimulation in 33% of the total. A further 7% have demonstrable seizures during IPS but report no visually precipitated attacks in everyday life. Thus, 80% of photosensitive people with epilepsy have some form of visually precipitated seizures. These are often associated with idiopathic generalized epilepsies and especially with juvenile myoclonic epilepsy, in which 30% to 48% are photosensitive, and childhood absence epilepsy, in which 18% were reportedly photosensitive.¹²⁵^,²⁰⁸ Typical absence seizures may be triggered by IPS: These are rare and may be resistant to treatment.¹⁰

Photosensitivity in Other Epileptic Disorders

Photosensitivity may be found in several epileptic disorders. It is rare in symptomatic occipital epilepsies but has been described with triggered focal occipital seizures in patients with
occipital calcifications and celiac disease.⁴ It also may occur with symptomatic generalized epilepsies such as severe myoclonic epilepsy of infancy (SMEI, Dravet syndrome); with the progressive myoclonus epilepsies such as Lafora disease, Unverricht-Lundborg disease, Kufs disease; or with the neuronal ceroid lipofuscinoses, in which photosensitivity at low flash frequencies such as 1/s is typical. These syndromes are associated with photic cortical reflex myoclonus, and the patients also have clear-cut action myoclonus.

Pattern-sensitive Seizures

Pattern-sensitive epilepsy consists of seizures triggered by viewing patterns, typically stripes. The seizures are generalized convulsions, absences, or brief myoclonic attacks provoked by viewing patterns such as patterned video screen content, escalator steps, striped wallpaper, or patterned clothing.²² Television is now the most common precipitant, reported in 41% of 73 patients.¹⁶⁵

Initially described in a single child by Bickford, it was considered an interesting rarity. Bickford et al.¹⁷ reported a low rate of EEG sensitivity to stationary pattern of 0.25% in 40,000 patients. Chatrian showed that the nature of the pattern affected its epileptogenicity, and the classic studies of Wilkins et al.²² further described the characteristics of epileptogenic patterns. With stimuli designed for maximum effect, pattern sensitivity is more common than previously reported, found in 17% to 54% of photosensitive subjects with static patterns.²¹^,¹⁰⁹^,¹⁴⁴^,¹⁶⁰ Patterns oscillating orthogonal to their line orientation are more provocative and elicit sensitivity in 60% to 70%.²¹ Clinical pattern sensitivity is much less common, found in about 2% of photosensitive subjects by Jeavons and Harding¹⁰⁴ and in 6% by Kasteleijn-Nolst Trenité.¹⁰⁹ Some subjects sensitive to pattern are not sensitive to flicker.⁹⁰ Radhakrishnan et al.¹⁶⁵ noted this in 11% of 73 subjects, but their first EEGs were performed in 1950 and this may be partly related to different methods of IPS and age-related changes in photosensitivity.

Interictal epileptiform EEG activity has been reported in 84%. Two thirds had generalized epileptiform activity with pattern stimulation, and in one third, this was confined to posterior head regions.¹⁶⁵ These authors also found that 14 of 73 (19%) had JME, three had progressive myoclonus epilepsy, and one had SMEI.

Other

Some photosensitive patients are sensitive to eye closure alone. Reflex absences or brief myoclonic attacks, and visual disturbances (“scotosensitive seizures”) can occur with eye closure or in darkness in patients not sensitive to intermittent photic stimulation and are thought to be precipitated in some by the abolition of central vision and fixation.¹⁵¹^,¹⁵² Others may not require total darkness or abolition of fixation. However, most subjects with the florid posterior epileptiform EEG activity abolished by fixation, and typical of the Panayiotopoulos and Gastaut types of idiopathic childhood occipital epilepsy, do not have reflex seizures.

Eyelid myoclonia with absences, described by Jeavons¹⁰³ and reviewed by Gobbi,⁷⁵ is characterized by eyelid jerks with eye closure in a photosensitive patient, with bilateral fast spike-and-wave EEG activity. The seizures can occur even in darkness. Some have no spontaneous seizures. Often, only the EEG change can be seen. Not all patients have absences and not all are photosensitive. It is not yet clear whether this forms a discrete clinical entity: The trigger mechanisms are complex and not well defined, and many may have another epileptic disorder such as JME. Harding and Jeavons⁹⁰ suggested that most such cases were examples of self-induction, but a detailed definition of a syndrome of eyelid myoclonia with absences has been suggested by Panayiotopoulos.¹⁵³

Seizures reportedly triggered by eye movement¹⁸³^,¹⁹¹ are a heterogeneous group. Some may represent scotosensitivity, and others may be cases of self-induction. Others triggered by conjugate eye movement may depend on proprioceptive input, and anterior, occipital, and parietal EEG discharges have been reported with these.

Self-induction of Visual-sensitive Seizures

Patients with all types of visually induced seizures may induce attacks with visual stimulation and may be compulsively drawn to sources of flicker or pattern stimulation such as television screens. Patients sensitive to eye closure may use a compulsively repeated eye rolling and eyelid flicker movement to self-stimulate.⁴⁷ Monitoring has shown that the stimulatory behaviors indeed trigger the seizures rather than being manifestations of the seizures. Intensely pleasurable sensations have been reported with these, and some patients induce seizures to relieve stress or to gain attention.¹⁸⁸ Monitoring indicates that 24% to 30%²¹ engage in self-induction when placed in a well-lit environment, particularly if stressed. Diagnostic features are:¹⁹

The eye movement precedes the epileptiform EEG discharge.
The oculographic artifact is larger and slower than that accompanying normal spontaneous eye closure and often shows a superimposed ocular tremor at about 6 Hz.
The maneuver is carried out less frequently in darkness, where it fails to produce epileptiform discharge.
The behavior is increased by stress.
Patients display guilt when the phenomenon is discussed.
Patients admit to carrying out the maneuver, variously describing it as voluntary or compulsive.
A pleasant sensation is often reported; this may have a sexual component leading to orgasm in some subjects.
There may be a history of seizures induced by hand waving in the past, or patients may use hand waving in combination with slow eye closure to enhance or prolong the discharge, as documented on film by Ames.⁵

These can be distinguished by EEG monitoring from nonepileptic paroxysmal eyelid movements that may occur in children and adults with generalized photosensitive epilepsy. These may be mistaken for absence seizures. There is often a family history of eyelid movements.²⁹

Seizures Triggered by Television and Video Displays

Reflex seizures triggered by television, computer screens, and video games have become notorious. The Pocket Monsters cartoon episode that triggered a nationwide outbreak of photosensitive seizures in Japan is a well-known example,⁸⁷^,¹⁰² but broadcasting of dangerous screen content had already led to outbreaks of photosensitive seizures, and guidelines to prevent the broadcasting of screen content likely to trigger seizures were already in place in the United Kingdom. These have become more widespread since the Pocket Monsters episode. Many of these events represent pure photosensitive epilepsy with or without pattern sensitivity. Some have occurred in subjects not previously known to have epilepsy, and others have occurred in known photosensitive patients. Some were likely focal occipital visual reflex seizures with autonomic manifestations (see IPOE above). Ferrie et al.⁵⁹ found that 29% of a group of subjects with video game–induced seizures had photosensitive partial seizures. In patients with seizures recurring after an initial Pocket Monster seizure, juvenile myoclonic epilepsy was the most common diagnosis in those not known to have epilepsy before the triggered event, while those with a history of epilepsy and recurrent seizures often had frontal lobe epilepsy.¹⁴⁹
Guidelines in Japan and the United Kingdom now prohibit such program material.⁹¹ These have been shown to successfully control potentially harmful TV screen content.¹⁸⁶ Special electronic filter devices are also effective in reducing PPRs induced by television.¹⁸⁵ Seizures associated with video screens may also have occurred by chance or in nonphotosensitive individuals in relation to other reflex seizure triggers, such as thinking, with or without manipulation of objects (action programming or praxis, see below) during computer use or game play.

Mechanisms of Visual-sensitive Seizures

Several approaches have been taken to studying human photosensitivity and seizures induced by visual stimuli. Visual stimulation resembling reported environmental stimuli such as video games can be modified and responses studied. Properties of elementary and subthreshold visual stimuli can be manipulated to enable inferences to be drawn about physiologic trigger mechanisms in both EEG and evoked potential studies and more recently in magnetic resonance and magnetoencephalography studies.

Television-induced seizures and others triggered by video displays can be understood in relation to the properties of video screens and to the images on the screen. Visual reflex seizures and the characteristics of the effective triggers have been recently reviewed.²¹⁴ Flicker rate, pattern, luminous intensity, size, location, and duration of the stimulus need to be considered. A television screen produces flicker at the alternating current (AC) frequency, effectively generating IPS at 60 Hz in North America and 50 Hz in Europe. Photosensitivity is more common at the lower frequency, with nearly 50% of patients sensitive to 50-Hz intermittent photic stimulation,¹⁰⁴ and television sensitivity has indeed been a greater problem in Europe than in North America. Television-induced seizures, however, are not only related to AC frequency flicker. Wilkins et al. studied patients who were not sensitive to this flicker but who responded to the vibrating pattern of interleaved lines at half the AC frequency (25 Hz in Europe and 30 Hz in North America) to which about 75% of photosensitive subjects are sensitive and which can be discerned only close to the screen.²⁰⁵ Special 100-Hz television screens, marketed in Europe, reduce the risk of television-induced seizures.¹⁶⁹ Color is important even without luminance changes; photoparoxysmal EEG responses can be elicited in sensitive subjects by non–color-opponent stimuli even if they are isoluminant.⁸⁸ Sensitivity is greater with red stimulation at wavelengths greater than 700 nm, and red stimulation was important in the Japanese cartoon incident.⁸⁷ Red-cyan flicker, even when isoluminant, is reportedly even more provocative of epileptic discharge.¹⁸⁰ Thus, seizures can be triggered even at greater distances and by 100-Hz TV sets and modern noninterlaced screens without intrinsic flicker. Flashing or patterned screen content has been implicated in these. Although the 50-Hz television screen is an important determinant of screen sensitivity and 100-Hz screens reduce the ability of the screen to trigger seizures, it is important to note that all systems are equally dangerous if dangerous screen content is broadcast.

Most patients sensitive to IPS can be shown to be sensitive to pattern, and studies on pattern-sensitive patients have enabled several inferences to be drawn, based also on animal studies of single unit responses. These have recently been reviewed by Wilkins et al.²⁰³ and can be summarized as follows:

The seizure trigger involves cortical cells. A paroxysmal EEG response occurs in the majority of patients with a history of photosensitive seizures when they are exposed to IPS. In about 30% of patients, bright, large, continuously illuminated patterns of high-contrast stripes evoke a similar, though usually less pronounced, response. The response is probabilistic and depends on the spatial and temporal properties of the visual stimuli that evoke it. Studies of length of line contour of effective patterns, pattern orientation, and the effect of binocularity indicate a cortical trigger. Further evidence comes from studies of effects of spatial frequency and of pattern motion: These suggest that the trigger involves neurons whose spatial tuning is independent of position in the visual field, and the first point at which this independence occurs is at the level of the complex cell in the visual cortex. EEG studies using patterns presented in only part of the visual field, such as hemifield stimulation, are also consistent with an occipital cortical event, and also indicate that seizure onset involves one cerebral hemisphere or both hemispheres independently. Often the response is generalized, involving many brain areas other than the visual cortex, but even in these circumstances the trigger may be cortical and unilateral because when the response is suppressed with sodium valproate, focal occipital activity can remain.⁴⁸ All these are consistent with an epileptic discharge triggered in the visual cortex, which sometimes remains within the visual cortex and sometimes spreads to involve other areas.

The triggering mechanism requires the physiologic activation of a critical area of cortical tissue. Any region of the visual cortex can evoke an epileptiform discharge, provided a sufficiently large area is stimulated. Wilkins²⁰¹ noted that the probability of a response to patterns differs in each patient, but in such a way as to indicate that each patient’s threshold can be expressed in terms of the area of cortex necessary to trigger a discharge.

Synchronization of the physiologic activation is necessary for epileptogenesis. Patterns that vibrate back and forth, orthogonal to their line orientation, become more epileptogenic, but a pattern that drifts steadily in the same direction ceases to be epileptogenic. This difference suggests an important role for the synchronization of large neuronal aggregates in the induction of a discharge. When the pattern alternately changes direction, the neurons sensitive to one direction of motion should fire, followed by a period during which cells sensitive to the opposite direction of motion should fire. The very marked difference in the epileptogenic properties of drifting and vibrating patterns suggests that the synchronization that occurs with a vibrating or phase-reversing pattern is critical at the initiation of the epileptic discharge.

The trigger involves the magnocellular pathways, but the resulting discharge may be more diffuse and involve both magnocellular and parvocellular divisions. Several characteristics of epileptogenic patterns suggest this involvement. The stripes differ in brightness rather than color, and are more epileptogenic if they move in certain ways and fuse in binocular vision. They have a rather low spatial frequency. Magnocellular neurons do not generally code for color, are directionally coded, and are tuned for binocular disparity. They have a lower spatial resolution and a higher temporal resolution than parvocellular neurons. The magnocellular system is thought to be part of the “dorsal stream,” and in pattern-sensitive patients, the isolated spikes in response to a pattern tend to be most marked over parietal electrodes. The cortical hyperexcitability need not be confined to this system but the discharge may start there. Harding and Fylan⁸⁸ also provide evidence for the participation of the parvocellular system.

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