Visual Sensitivity and Epilepsy: A Proposed Terminology and Classification for Clinical and EEG Phenomenology

Authors


Address correspondence and reprint requests to Dr. D. G. A. Kasteleijn-Nolst Trenité at Stichting Epilepsie Instellingen Nederland, Meer & Bosch, Achterweg 5, 2103 SW Heemstede, The Netherlands. E-mail: dkasteleijn@planet.nl

It has been known for more than a century that flickering sunlight can provoke epileptic seizures in susceptible patients (1). However, the modern technologic environment has led to a dramatic increase in exposure to potential trigger stimuli. Outbreaks of visually induced seizures were reported after the introduction of the television set (2), of video games (3), and of television commercials and programs (4,5). Other provocative visual stimuli in the contemporary environment include discotheque lighting, rolling escalators (a moving, striped pattern), and rotating helicopter blades (6–9). Such epidemics of visually induced seizures have been a source of great concern to the general public (10).

Although much research has been undertaken since the 1950s (4,8,11–14), many questions concerning underlying basic mechanisms and clinical semiology remain unanswered, and the terminology of clinical and EEG phenomena is not yet standardized.

An initial step has been taken through the publication of proposed international standards for intermittent photic stimulation (IPS) (15).

We present a proposal for the terminology and classification of clinical and neurophysiologic phenomena relating to visual sensitivity. It aims to standardize the use of clinical terms and definitions. This proposal is divided into four main areas:

  • a. Clinical symptoms of visual sensitivity.
  • b. Classification of the EEG responses to IPS.
  • c. Classification of electroclinical phenomena.
  • d. Syndromic classification.

Commonly used terms such as photosensitive, photogenic, and photoconvulsive, which have different and inconsistently used connotations, have not been used to avoid any misunderstanding. A distinction has been made between the epileptiform EEG responses to IPS [so-called photoparoxysmal responses (PPRs)] and clinical signs and symptoms, evoked either by IPS or by visual stimuli in daily life. If a PPR is found, the patient is considered IPS sensitive. Visual sensitivity is defined as the susceptibility toward experiencing seizures, which are triggered by the physical characteristics of visual stimuli and not by their perceptual properties (i.e., reflex seizures induced by the cognitive effects of visual stimuli).

A combination of these data with a clinical seizure history and imaging results will assist identification of the various syndromes, thus leading to an assessment of risk factors and prognosis in the various patient groups.

PATHOPHYSIOLOGY

Visual-induced epilepsy has a strong genetic component. Siblings of children with generalized PPRs are much more likely to show a similar abnormality than are siblings of control subjects (19.3 vs. 3.4%) (16). A PPR is also significantly more common in 5- to 10-year-old siblings of proband offspring of a parent with a PPR (50%) than in siblings of PPR-positive children of parents without a PPR (14%) (17).

Studies performed in humans and in experimental animal models, especially the Papio papio baboons, which respond to IPS at 25 Hz with epileptic seizures resembling those of photosensitive patients, indicate that the cerebral cortex plays a primary role in the genesis of electroclinical manifestations of visual-sensitive epilepsy (18). The frontorolandic cortex and the occipital cortex seem to be the most involved in generating the abnormal response in both species. Unitary recording in the baboon shows that the photoparoxysmal EEG response originates from the frontorolandic cortex (19). Generalized seizures appear to result from spread of seizure activity, which is initiated by IPS in the frontorolandic cortex (18). Blockade of frontorolandic discharges by local γ-aminobutyric acid (GABA) infusion also blocks IPS-induced grand mal seizures (20). However, visual afferents to the frontorolandic cortex are controlled by the occipital cortex, which can generate epileptic activity on its own if made hyperexcitable by a decrease in the level of GABA by alloglycine injections (21). Depressants of photosensitivity in the baboon such as valproic acid (VPA) also are active in humans. Despite many striking similarities, the relationship between the IPS-sensitive baboon and patients with photic-induced seizures has been questioned (22,23).

Neurophysiologic studies in patients with photic reflex myoclonus (24–26) show that the contralateral occipital cortex is activated first and that impulses spread to the primary motor cortex to produce myoclonic jerks. In addition, numerous reports indicate that in a considerable number of individuals with visually induced seizures, ictal activity originates from the occipital cortex (13,27,28). Subsequent spread to the suprasylvian cortex often results in generalized tonic–clonic seizures (GTCSs), whereas infrasylvian spread produces complex partial seizures (see also partial seizure section).

Studies in pattern-sensitive epilepsy revealed that the two hemispheres can have a different threshold; that a critical area of the visual cortex should be stimulated, and that synchronization of neural activity is necessary to elicit a PPR (29). The corpus callosum is critical for interhemispheric synchronization and generalization of EEG discharges (30).

Visually evoked potentials (VEPs) of different contrast show that for stimuli of low to medium frequency, the contrast dependence of VEP amplitude and latency is remarkably abnormal for luminance-contrast, but not so for chromatic-contrast stimuli (14). These data indicate that patients with visually induced seizures lack the normal mechanisms of cortical gain control for pattern stimuli of low temporal frequency and high luminance. Suppression of contrast gain control may be experimentally induced in the cat by local application of bicuculline (31), indicating that reduced GABAergic transmission plays a role in visual cortex hyperexcitability. In patients with progressive myoclonus epilepsy, the mechanism of visual sensitivity has been related to deficit in dopaminergic transmission, because apomorphine, a dopaminergic agonist, abolished the PPRs (32). Many antiepileptic drugs (AEDs), developed for partial and generalized seizures, have reduced or abolished PPRs in humans, suggesting that a variety of neurotransmitters and channel blockers could be involved (33,34).

CLASSIFICATION OF THE CLINICAL SYMPTOMS

Mild subjective symptoms

Some individuals may complain of subjective symptoms when they are exposed to photic stimuli, especially IPS (35). Some of these symptoms are normal phenomena, due to the effect of intense light stimuli. They consist of seeing zigzag lines or colors not actually present in the stimuli. Other symptoms include dizziness, eye pain, dragging sensations in one eye, epigastric discomfort, nausea, or simple visual hallucinations. These manifestations may be unrelated to epileptic activity or they may result from an ictal discharge arising in the occipital cortex (27,36) or in the mesial temporal structures (37). An accurate clinical diagnosis regarding the nature of mild subjective symptoms can be very difficult if the duration is short and their occurrence infrequent. Some of these subjective manifestations may be definitely ictal but still remain isolated symptoms, which is sustained as long as the triggering stimulus is sustained. On other occasions, they may be part of a more complex ictal episode, if a self-sustained ictal discharge arises and spread occurs (see Partial seizures section).

Orbitofrontal photomyoclonus

Frontopolar, recruiting, photomyogenic, and photooculoclonic responses are synonymous with orbitofrontal photomyoclonus. The triggering stimulus is IPS. The frequency range of flashes effective in triggering this response is usually between 8 and 20 Hz. It is rarely seen in children, but constitutes a normal finding in adults and, in particular, in the elderly. Patients have rapid myoclonic jerking of the periorbital muscles, which produces eyelid fluttering and blinking, synchronous with the flashes. There may be vertical oscillations of the eyeballs. Amplitude of the response increases progressively during the first flashes, reaching a maximum within a few seconds. The maximal amount of muscle activity is initially observed in the inferior orbicularis oculi muscles, with subsequent irradiation to other facial muscles, the frontal and occipital areas, and the neck (38). Further spread may be seen if IPS stimulation continues. The likelihood of eliciting this response is increased by muscular tension, for instance, if one were to instruct the subject to screw up the eyes and clench the jaws. This response is bilateral and time-locked to the stimulus. Latency between each flash and the corresponding muscle contraction is ∼50–60 ms. Response is blocked when the eyes are opened, and it stops immediately when the stimulation is terminated. Although the physiology and significance of this response have been disputed for a number of years, our current understanding indicates it to be an expression of cortical response (39) within the spectrum of photic cortical reflex myoclonus (25,26).

Eyelid myoclonus

Eyelid myoclonus may occur either as a very short event lasting ∼1–2 s without any detectable impairment of consciousness or as in Absences with eyelid myoclonus, be prolonged and accompany an absence seizure (40). Eyelid myoclonus must be differentiated from the orbitofrontal photomyoclonus (OPM, see earlier), because its clinical and electrographic relation to epilepsy is obvious. The delay between the stimulus and ensuing eyelid jerking is longer than that seen in the photomyogenic response and is more variable (41).

Self-inducing behavior (SI)

In some patients, myoclonic jerking of the eyelids appears in the context of a complex repetitive self-stimulation habit with deliberate fluttering of the eyes and hyperextension of the head in front of any bright light source, including IPS. Under these circumstances, attempting to draw any distinction between eyelid myoclonus and self-inducing behavior may be particularly difficult.

Focal, asymmetric myoclonus

In exceptional cases, focal myoclonic (FM) jerks (e.g., in one hand, arm, or hemiface) can be evoked by IPS (35,42). Consciousness is retained.

Generalized myoclonus

Generalized myoclonic jerks are usually symmetric and predominate in the upper limbs. In most cases, they are mild, producing only nodding of the head and slight arm abduction. More generalized jerks, involving the face, trunk, and legs, may occasionally cause the patient to fall. The relationship of myoclonic jerks to the stimulus is complex. Sometimes there is no definite time relationship. On other occasions, the jerks may be repeated rhythmically with the same frequency as the stimulus or at one of its subharmonics (11).

Without loss of consciousness, often isolated

Isolated myoclonic jerks occur without impairment of consciousness.

With impairment of consciousness

However, generalized jerks may be repeated, especially if the stimulus continues. In this situation, consciousness may be impaired, and a GTCS may follow.

Tonic, versive phenomena

On rare occasions IPS has been shown to produce version of the eyes and the head toward one side. The versive posture (TVP) may be sustained as long as the triggering stimulus is continued (43), representing a stimulus-dependent localized ictal phenomenon. It may also outlast the stimulus as a feature of a simple partial seizure that may then evolve to complex partial or to a GTCS. In this case, it indicates that focal seizure activity precedes seizure generalization.

Absence seizures

A small subgroup of patients has loss of awareness as the only symptom. When stimulation is performed with the eyes being held closed, the absences may be manifested only by opening the eyes. Mean age at onset is ∼12 years (4). Absences may outlast the stimulus. A mild myoclonic component and evolution into a GTCS are possible.

Generalized tonic–clonic seizures

These are usually, but not always, triggered after sustained exposure to photic stimuli. They may follow an absence, a myoclonic jerk, a series of jerks, or a partial seizure, but can occur without any preceding phenomenon. Secondary generalization may be slow or very fast, after mild clinical signs such as head deviation or visual symptoms, which could possibly indicate generalization of an initially focal, possibly occipital seizure.

Partial seizures

In up to 65% of patients with photic-induced seizures, focal ictal onset, usually in the occipital neocortex, is clinically demonstrable (27,28). Photically induced PS is often characterized by a sequence of visual and vegetative symptoms, sometimes accompanied by headache (36,44). These seizures can be mistaken for migraine, especially if motor manifestations are not recognizable.

Clinical seizure semiology is similar to that of spontaneous occipital-onset seizures. Spread may be rapid, but it must be stressed that it can also be remarkably slow, occurring after many minutes of ictal activity limited to the occipital lobe (13,18,45,46).

With simple visual symptoms

Most patients experiencing subjective symptoms describe visual phenomena as the initial ictal manifestation. These are usually reported as bright, multicolored, or occasionally manifesting dark rings, spots, or simple geometric forms, which are continuous or flashing. Location is usually, but not necessarily, in the periphery of the visual field, crossing to the opposite side while rotating or moving slowly (36,44,47). Ictal amaurosis, blindness, or severe blurring of vision, limited to one quadrant, hemifield, or involving the entire visual field, may follow the visual hallucinations but may occasionally constitute the first symptom (46,48,49). It can be impossible to distinguish between ictal and postictal blindness.

With complex visual symptoms

More complex visual hallucinations may include scenes often related to past experience and may be accompanied by macropsia, micropsia, or perceived scenes of people or animals described as static or moving horizontally, approaching or receding.

Illusions also may include alterations in the size, shape, or motion of objects, a change in color perception manifested by monochrome vision, or diminished intensity of hue (achromatopsia). More complex illusions may result in an altered perception of objects in space, accentuating distance or proximity (50). Ictal palinopsia (i.e., the persistence or recurrence of visual images once the real object of perception is no longer present) is reported fairly frequently (51). As this phenomenon often co-occurs with hallucinations, there may be difficulty in distinguishing the two components. Visual phenomena are often accompanied or followed by “conscious” tonic or, rarely, clonic eye, or eye and head deviation, usually toward the side of the initial visual symptoms. Clinically, it may be impossible to determine whether eye and head turning are manifestations of the seizure or whether they are attempts by the patient to follow perceived images and hallucinatory figures.

Eyelid fluttering or forced blinking with a dragging sensation in one eye represent other seizure manifestations that have been correlated to occipital localization of seizure discharges. Visual phenomena, both positive and negative, may spread to involve the entire visual field.

Propagation of seizure activity to mesiotemporal limbic structures is frequent (52,53), and accompanied by automatisms typical of temporal lobe epilepsy. The most frequent ictal pattern is a sequence of epigastric discomfort, unresponsiveness, and automatisms. Some patients experience vomiting, which seems to be particularly frequent during the course of prolonged seizures triggered by photic stimulation (36,44). Suprasylvian propagation to the lateral motor cortex is accompanied by focal motor or hemiclonic activity and propagation to the supplementary sensorimotor cortex by asymmetrical tonic posturing (46,47,54).

With early limbic symptoms

In exceptional cases, it has been demonstrated that visual stimuli can induce simple PSs with vegetative symptoms or an epigastric aura, without any preceding visual manifestations(27).

CLASSIFICATION OF THE EEG RESPONSES TO INTERMITTENT PHOTIC STIMULATION

Photic following

At flash rate

Confluent VEPs to successive stimuli producing a regular activity at the flash frequency, ending as soon as the stimulus train was terminated. This is a typical, normal response.

At harmonics

Regular activity at a sub- or supraharmonic of the flash frequency, ending in conjunction with the stimulus train. It is often intermixed with following at the flash rate. It is normal and of no clinical significance if symmetric.

In about 5% of patients, an abnormal asymmetric driving response (>50% difference in amplitude) can be found (55).

Orbitofrontal photomyoclonus

Bioelectrical signals elicited by successive stimuli producing a regular activity at the flash frequency, which ends as soon as the stimulus train is terminated. It was first described as a myogenic response by Gastaut (42) and termed “photomyoclonus” by Bickford et al. (38). The signals are predominantly of electromyographic origin, arising in the orbicularis oculi and frontalis muscles in particular, and are therefore maximal at the front of the head. A cerebral component of frontal lobe origin may also be present (27).

Photoparoxysmal responses

Grades 3 to 5 are commonly known as “photoparoxysmal responses” and include the four types of the classification of Waltz et al. (56) and of the three responses (GSW, OGSW, and OSW) of the European consensus (57). It is still unclear to what extent the finding of one of these responses is related to risk of visually induced seizures, because apart from methodology of IPS, age and (duration) of medication also have influences on the type of response. However, a generalized response at a wide range of flicker frequencies (photosensitivity range) is considered specifically to be of clinical importance.

Posterior-stimulus-dependent response

Anomalous steady-state VEPs, of unusually sharp waveform or high amplitude. Some types have clinical correlates, for instance, occipital spikes after suppression of generalized PPR by medication and high-amplitude VEPs in neuronal ceroid lipofuscinosis (58).

Posterior stimulus-independent responses

Limited to the stimulus train

Activity confined to or maximal at the back of the head and not at the flash frequency or at a harmonic thereof. The term includes delta and theta activity and frank epileptiform patterns.

Self-sustaining

Self-sustaining posterior stimulus-independent responses that outlast the stimulus train. These often last many seconds and may evolve to an overt seizure.

Generalized photoparoxysmal response

Limited to the stimulus train

Comprises multiple spikes or spike-and-wave activity, which are apparently generalized, but may be of greater amplitude at the front or back of the head. It is termed a “photoconvulsive response (PCR)” by Bickford et al. (38), and corresponds to type 4 response of Waltz et al. (56).

Self-sustaining

Generalized PPR continuing after stimulation. This may not be demonstrated unless the stimulus train is terminated as soon as a generalized PPR is identified (59). It was termed “prolonged photoconvulsive response” by Reilly and Peters (60), and has a strong association with epilepsy and visually induced seizures in patients referred for clinical EEG examination (7). Its prevalence in asymptomatic general populations is unknown, but was found in five of 13,658 apparently healthy aircrew by Gregory et al. (61).

Activation of preexisting epileptogenic area

Rarely, photic stimulation may activate an epileptogenic cortex, which is also spontaneously active; IPS could then also elicit a seizure by stimulating this, usually posterior located, area (62). It is questionable whether this should be considered a PPR, and it does not figure in established classifications.

CLASSIFICATION OF ELECTROCLINICAL PHENOMENA

We know for certain only that if the response to IPS is generalized, the likelihood of having epilepsy ranges from 70 to 90%(7,59,60), and the likelihood of having visually induced seizures is ∼60%(7). The risk of having seizures is lower (30%) in patients with PPR but without spontaneous epileptiform EEG discharges (63). The only contemporary study on other types of photically induced responses is a retrospective study on the inheritance of photosensitivity (type 1–4, Waltz classification) and epilepsy (17). They found that the lowest seizure risk was among siblings of ages 5–15 years who were not sensitive to IPS (4%) and who were born of similarly nonsensitive parents. The highest risk was found among IPS-sensitive siblings of equal age range (33%) with a PPR in one of their parents.

Myoclonic jerking evoked by IPS is highly related to a clinical history of epileptic seizures outside the laboratory (64).

We therefore propose a flexible system to create a distinction between the various groups. With an evolution of the clinical picture or the availability of more detailed clinical information, patients could switch from one category to the other. In due course, the total number of categories could be diminished.

Individuals with a photoparoxysmal response in the EEG and no history of epileptic seizures

The PPR can be detected by chance among individuals with headache or another complaint, candidate aircrew, or because of a family member with epilepsy or photosensitivity (9,61,65,66). Studies performed in the 1950s and 1970s in normal subjects revealed a prevalence of abnormal EEG responses to IPS between 0.5 and 5% (children and adolescents, 4%) (67,68). If the IPS-evoked response is a generalized PPR, the likelihood of developing epileptic seizures is ∼20% in the selected group of aircrew personnel screened for EEG abnormalities. In 80% of patients older than 30 years being referred for general EEG diagnostics [psychiatry, cerebrovascular accident (CVA), head injury, alcoholism, headache etc.], the occurrence of a generalized PPR was related to a history of epileptic seizures (65,69). Criteria for an abnormal response to IPS were, however, flexible and included diffuse paroxysmal slow activity and spikes without generalization.

To rule out the possibility of minor visually induced seizures (see earlier), a detailed clinical history should be taken with the emphasis on subtle, subjective symptoms. Ocular discomfort, such as pain in the eyes or blurring of vision, can be considered an ictal symptom (7,35). A distinction between an ictal visual aura (or complaint) and atypical complaints, such as tears and seeing diffuse colors, can be difficult to draw. If in doubt, the patient can be classified in this category with ocular discomfort as a remark.

When a PPR is found in a child, the reaction to IPS may increase during adolescence, leading to a clinical seizure (70).

Patients with spontaneous seizures only, but a photoparoxysmal response in the EEG

A PPR can be found in several epilepsy syndromes (see later) (71). To determine whether seizures are spontaneous, detailed questioning should be carried out concerning the circumstances in which seizures appeared. It may be helpful to give the patient cues on possibly provocative visual stimuli (e.g., sunlight through trees, television, disco flashes, striped clothes, escalators). If, in addition to a clinical history of spontaneous seizures, clear reproducible clinical signs are seen during the IPS-evoked PPRs, the patient is considered to have visually induced and spontaneous seizures, with or without a PPR in the EEG (type 5, see later).

Patients with an isolated visually induced seizure, with or without a photoparoxysmal response in the EEG

This comprises a single seizure in front of the TV, in the disco, while playing a computer game, and so on, whether or not under special circumstances (e.g., sleep deprivation, fever, alcohol withdrawal, menstruation). On such evidence, it would be impossible to determine whether the seizure was visually induced; subsequent events could require reclassification of these patients.

Recurrent visually induced seizures only, with or without a photoparoxysmal response in the EEG

These patients have a clear history of seizures (most often myoclonic jerks and GTCSs) exclusively in response to a visual stimulus. The finding of a PPR is dependent on the IPS laboratory technique used, as well as on the age of the patient and the use, type, and dosage of AEDs (15,72,73).

Visually induced and spontaneous seizures, with or without a photoparoxysmal response in the EEG

A combination of both visually induced and spontaneous seizures may be found either in children with severe epileptic encephalopathies and early-onset photosensitivity (74) or in otherwise normal intelligent children and adolescents (7,75,76).

SYNDROMIC CLASSIFICATION

The International Classification of epilepsies (77) did not recognize visual sensitivity (VS) or IPS sensitivity only, as characteristic of any given epileptic syndrome, nor did it consider that VS justifies the individualization of a “photogenic epilepsy.” There is indeed agreement among clinicians and researchers that VS and IPS sensitivity belong to various forms of human epilepsies. As a trait, a PPR or VS can be found in generalized or localization-related, idiopathic, cryptogenic, or symptomatic epilepsies, and even within the context of situation-related (acute symptomatic) seizures.

A PPR may occur in patients with epilepsy as a incidental finding with no particular significance, and with no apparent relationship to the seizure disorder (see earlier). However, such situations are uncommon. In most patients with epilepsy and a PPR, the presence of the PPR is significantly related to the pathophysiology and clinical aspects of the epilepsy and has practical consequences, although the pharmacologic sensitivity, course, and prognosis of such epilepsies are not reliant on this trait alone. The most frequent association between IPS sensitivity, VS, and epilepsy occurs in idiopathic generalized epilepsies.

GENERALIZED EPILEPSIES

Idiopathic generalized epilepsies

Visual sensitivity is particularly frequent in IGEs, in which it can be found in different age ranges, but it is most common in children and adolescents of ages 8–25 years. There is a clear female predominance among patients with VS and IGE. The triggering role of visual stimuli tends to decrease through adulthood, although the PPR may persist on repeated EEG investigations (23,70,78).

Benign myoclonic epilepsy in infancy is the earliest presenting form of IGE associated with VS (74). It is characterized by onset before the age of 1 year. Generalized spike-and-wave (SW) discharges are always associated with myoclonic jerks and can be elicited by IPS.

Childhood absence epilepsy (CAE), in its typical, pyknoleptic presentation, is associated with PPRs and VS in 13–18% of patients; no gender difference is found between those with and without a PPR. A preponderance of females is seen in both (79,80).

Juvenile-onset absence epilepsy (JAE) is accompanied by VS or PPRs in 8% of patients (80).

Juvenile myoclonic epilepsy (JME) is the form of epilepsy that has the closest association with VS (80). Thirty to thirty-five percent of patients (up to 40–45% of females) exhibit a PPR, although the prevalence of clinical visual sensitivity may be lower. It is unknown whether this IPS-sensitive subgroup also has a lifelong occurrence and a high relapse rate after a discontinuation of medication.

Epilepsy with GTCS on awakening is accompanied by a PPR in 13% of the patients, but this prevalence is lower in IGEs with GTCS that do not specifically occur at awakening (4–10%) (71).

Primary reading epilepsy, although previously classified as localization-related form of epilepsy, is now considered to be closely related to JME (81). It is associated with PPRs, evoked by IPS or pattern in fewer than 10% of cases (82).

Visual sensitive IGE, in which VS is associated with absences, including autosomal dominant absences exclusively appearing on light stimulation (83) and absences with eyelid myoclonus (40). Among IGEs, there is a significant subgroup of patients with seizures provoked by specific triggering factors, and VS is the most common of such factors. Many of these patients cannot be assigned to a main category of IGE but share with the other forms of IGE many characteristics including pharmacologic sensitivity and overall prognosis. Thus such patients can be categorized as having a visual-sensitive IGE, although it is not clear at this time whether this entity corresponds to the coincidence of different genetic traits or to a single mechanism.

Cryptogenic generalized epilepsies

Epilepsy with myoclonic-astatic seizures

Visual sensitivity is not common in patients with the Lennox–Gastaut syndrome and other forms of cryptogenic or symptomatic generalized epilepsies, an exception being myoclonic–astatic epilepsy of early childhood. Although in this form of epilepsy, a PPR is often found during childhood (84), little is known about its clinical correlates and prognosis.

Symptomatic generalized epilepsies and epileptic encephalopathies

Progressive myoclonus epilepsies

VS are often apparent both clinically and as an EEG trait (85,86). Rarely it may be the first symptom of the disease. It is often associated with giant somatosensory and VEPs. Among the most frequently encountered forms of PMEs in which an abnormal response to IPS is an important trait are:

Neuronal ceroid lipofuscinoses (NCLF) include clinically and genetically heterogeneous storage disorders, which can be found in very young patients, but also in adults. Visual sensitivity is found especially in the late infantile and adult forms (87,88). This may be characterized by a PPR, but particularly by high amplitude of following responses to low-frequency flicker and giant evoked potentials to single flashes. Patients with NCLF experience progressive loss of vision, and VS may decrease during the progression of the disease.

Lafora's disease; VS is a major trait persisting throughout the evolution. In this condition, VS is often associated with spontaneous focal occipital seizures (89,90).

Unverricht–Lundborg's disease; VS is a major, early clinical, and EEG trait that tends to remit after the second or third decade of evolution (personal communication); the clinical course of the disease is variable and differs between families (91).

Myoclonus epilepsy and ragged red fibers (MERRF); the clinical spectrum is extremely broad and VS may occur (92).

Other rare degenerative disorders

A PPR has been found in a so far unknown degenerative disorder with megalencephaly, spasticity, ataxia, and seizures (93).

In the lysosomal disorder type III Gaucher's disease: abnormal responses to IPS have been described (94). A case report has been published on Alzheimer and VS (95).

LOCALIZATION-RELATED EPILEPSIES

Idiopathic partial epilepsies and symptomatic and cryptogenic partial epilepsies

A PPR can be found in focal epilepsies associated with various types of lesions, and also in “cryptogenic” forms (27). A characteristic type of idiopathic occipital lobe epilepsy sensitive to visual stimuli has recently been reported (36). Onset occurs in late childhood or adolescence, with a pattern of visually induced occipital lobe seizures that may spread anteriorly. This form of epilepsy is often mistaken for migraine.

UNDETERMINED EPILEPSIES

Severe myoclonic epilepsy of infancy

This is associated with a PPR in 30–40% of cases (96), which are often accompanied by myoclonic jerks. The exact prevalence of clinical VS is not known, as children may manifest visually induced myoclonic jerks or absence in front of complex patterned stimuli. Onset may be very early, for example, in the first 2 years of life. Both clinical and EEG features of VS may disappear during the follow-up.

SITUATION-RELATED AND OCCASIONAL SEIZURES

In a variety of circumstances, seizures, usually GTCSs, can be elicited by visual stimuli in patients who cannot be considered as having epilepsy. The most frequent circumstances are:

Strong provocative visual stimuli in patients with latent VS

Exposure to strong visual stimuli in patients who may have a genetic trait of VS, coinciding with other precipitating factors such as sleep deprivation, fever, or stress (97,98).

Alcohol withdrawal, drugs, vitamins, toxic drugs

Alcohol or benzodiazepine (BZD) withdrawal may cause VS (99), as can the use of potentially epileptogenic drugs such as neuroleptics and antidepressants. Isoniazid has also been associated with de novo appearance of VS (100–104).

Thus, VS and PPRs are widely distributed throughout the different categories of epilepsy and are significantly associated with a variety of epileptic syndromes of different etiologies. Further investigations on prevalence and prognosis are necessary.

Acknowledgment: The workshop “Visual Sensitivity in the Modern Environment” in Aix en Provence, October 1999, was made possible by an unrestricted educational grant from Sanofi-Synthélabo. Participants were E. Andermann, F. Andermann, P. Bonanni, M. Beaussart, G.J. van der Beld, Y. Ben Ari, C. D. Binnie, P.R.M. de Bittencourt, M. Brinciotti, M. Bureau, G. Capovilla, P. Chauvel, A. Covanis, M.A. Danesi, C. Dravet, P. Gélisse, P. Genton, P. Groen, R. Guerrini, G.J. de Haan, G. Harding, I.E.J. Heynderickz, Y. Inoue, J. Isnard, D.G.A. Kasteleijn, G. Kramer, A. Martins da Silva, B. Martins da Silva, H. Meeren, B. Meldrum, R. Naquet, J. Parra Gomez, V. Porciatti, S.Ricci, J. Roger, G. Rubboli, M. Seino, S. Seri, S.R.G. Stodieck, T. Takahashi, C.A. Tassinari, P. Thomas, S. Waltz, A. Wilkins, B. Zifkin.

We deeply regret the loss of our colleague and friend, Stefano Ricci, who made a valuable contribution to this work.

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