Photosensitive epilepsies

INTRODUCTION — Reflex epilepsies are characterized by epileptic seizures that are evoked by specific external sensory stimuli, internal cognitive and emotional processes, or activity of the patient.

Photosensitive epilepsies constitute a heterogeneous group of reflex epilepsies that are triggered by visual stimuli [1]. This review will focus on photosensitive epilepsies, including photosensitive occipital lobe epilepsy, epilepsy with eyelid myoclonia (Jeavons syndrome), and Sunflower syndrome.

Other reflex epilepsies are reviewed separately. (See "Reflex seizures and epilepsy".)

PATHOPHYSIOLOGY

Photoparoxysmal response — Photosensitive epilepsy is characterized by a photoparoxysmal response (PPR) (epileptiform activity on electroencephalogram [EEG]) provoked by intermittent photic stimulation (IPS) consisting of repetitive flashes of light [2]. A classification of PPR patterns includes four grades [3]:

●Grade I – Occipital spikes

●Grade II – Parieto-occipital spikes with biphasic slow waves

●Grade III – Parieto occipital spikes with biphasic slow waves and spread to frontal regions

●Grade IV – Generalized spike/polyspike-and-wave discharges

Of these, a generalized response (grade IV PPR) is considered clinically important, having the strongest association with epilepsy [4]. However, some patients with photosensitive occipital lobe epilepsy may have only a localized PPR [5,6].

A PPR may be present in approximately 0.5 percent of the general population (range 0.3 to 8 percent), approximately 3 percent of people with focal epilepsy, and approximately 15 percent of people with generalized epilepsy [1,6-8].

Occipital cortex hyperexcitability — In photosensitive patients who exhibit a PPR, evidence from structural and functional imaging studies of the brain (functional magnetic resonance imaging [fMRI], diffusion tensor imaging, positron emission tomography, transcortical magnetic stimulation, and magnetoencephalography) have implicated hyperexcitability of the occipital cortex and altered visuomotor connectivity of cortical and subcortical networks as mechanisms involved in the initiation and spread of the PPR [9,10].

Neural gamma oscillations of 30 to 80 Hz in occipital cortex may play a role in seizure generation [11]. EEG techniques like gamma wave detection have shown neuronal synchrony with photic stimulation [11,12].

Genetics — Genes like SCN1A, BRD2, SCNM1, CHD2, and SYNGAP1 have been linked to syndromes in which photosensitivity plays an important role. As an example, in a study of 53 patients with SCN1A-related Dravet syndrome, IPS evoked a PPR on EEG in 40 percent of cases [13]. (See "Dravet syndrome: Genetics, clinical features, and diagnosis".)

Potential photosensitivity loci have also been detected in patients with juvenile myoclonic epilepsy on chromosomes 6, 7, 13, and 16 at regions 6p21.2, 7q32, 13q31.3, and 16p13 [14,15]. Most likely, an interaction among various loci is necessary for PPR susceptibility [16]. (See "Juvenile myoclonic epilepsy".)

EPIDEMIOLOGY — Photosensitive epilepsies together are the most common and well-known type of reflex epilepsy, making up approximately 5 percent of all reflex epilepsies. While estimates vary by age and population, photosensitive epilepsies comprise 2 to 10 percent of all patients with epilepsy [17-19]; the highest prevalence is found in younger patients, particularly adolescent females [6,20]. Unlike other reflex epilepsies, people of European descent are commonly affected. In a study from the United Kingdom, the estimated annual incidence of photosensitive epilepsy was 1.1 per 100,000, or approximately 2 percent of all new epilepsy cases [18].

CLINICAL FEATURES — The provoking visual features in patients with photosensitive epilepsy are related to flash frequency (especially 10 to 30 flashes per second), intensity of light, duration of stimulus, retinal coverage, and particular patterns and colors (black-and-white stripes and pure red) [1].

Certain visual stimuli, such as sunlight and flickering artificial lights, especially evoke myoclonus of eyelids, neck, and whole body. Approximately 25 percent of photosensitive patients will experience absence-type or focal (occipital and parieto-temporal) seizures. Pattern stimulation evokes predominantly absence and focal seizures (occipital seizures) [21]. Some patients with photosensitivity try to avoid strong visual stimuli by looking away; a small but intriguing subset with Sunflower syndrome shows the opposite behavior.

The clinical features of photosensitive epilepsies vary by phenotype.

Photosensitive occipital lobe epilepsy — With photosensitive occipital lobe epilepsy, the age of onset ranges from 4 to 12 years. Seizures are precipitated by light stimulation, particularly video games or television. The seizures are typically focal, consisting of visual blurring, hallucinations, or blindness, lasting for approximately a minute and, in some cases, progressing to generalized tonic-clonic seizures [5,6]. The seizures may be accompanied by head and eye version or vomiting.

Epilepsy with eyelid myoclonia (Jeavons syndrome) — Epilepsy with eyelid myoclonia (EEM) is a female-predominant generalized epilepsy syndrome characterized by eyelid myoclonia, photosensitivity, and eye-closure induced seizures or paroxysms on EEG [22]. A positive family history is present in up to one-half of patients [6,22]. Onset occurs from 3 to 12 years of age [22]. Seizures are provoked by eye closure, which results in loss of fixation. While loss of fixation has been implicated as a provoking stimulus, eyelid closure itself is thought to be the more important inciting factor [23]. Seizures are characterized most often by eyelid myoclonia (brief, repetitive upward myoclonic jerks of the eyelids, with upward eye deviation and sometimes with head jerks), absences, and, less often, with generalized tonic-clonic seizures [22,24-26]. Seizures usually persist into adulthood; earlier age at onset has been associated with an increased risk of intellectual disability and drug-resistant epilepsy [27].

An international expert consensus panel stressed that EEM is often underdiagnosed and that a correct diagnosis can only be made with electroencephalography (EEG) including photic stimulation [22]. Patients may not be aware of isolated eyelid myoclonus, which may contribute to delay in the diagnosis [24].

Sunflower syndrome — Sunflower syndrome is a rare photosensitive epilepsy characterized by heliotropism (a compulsive attraction to sun or light) and stereotyped seizures (table 1) [28,29]. The age at onset ranges from two to eight years (average six years) [29]. Patients typically present with hand-waving episodes; whether these are a manifestation of seizure activity, a method of seizure self-induction, or both, remains controversial [28-31]. These hand-waving episodes are described as "pausing when in bright sunlight, turning their bodies toward the sun, and extending their elbows outwards while lifting one of their hands to wave in front of their eyes" [29]. Patients may also exhibit hand-waving episodes in the presence of artificial bright light. In addition, patients may have other seizure types, including absence, eyelid myoclonia, and/or generalized tonic-clonic seizures.

Cognition may be normal, but cognitive and/or behavioral conditions, mainly attention deficit hyperactivity disorder and intellectual disability, have been reported in approximately one-half of patients with Sunflower syndrome [32-34].

Many experts, including the authors, consider Sunflower syndrome to be an example of a self-induced epilepsy, often acknowledged by the patient themselves; hand-waving episodes and other behaviors, including repetitive eye fluttering or slow eye closures, imitate a flashing visual stimulus that induces a photosensitive seizure, which in some reports is accompanied by pleasurable or even erotic gratification [33,35-37]. Other experts cite evidence that, at least in some patients, hand-waving is part of the seizure itself rather than a means of inducing a seizure [29,38,39].

There is overlap between Sunflower syndrome and Jeavons syndrome (table 1) [1].

Idiopathic and genetic epilepsy syndromes — Photosensitivity is also a common feature in many generalized epilepsy syndromes, including [1]:

●Juvenile myoclonic epilepsy (see "Juvenile myoclonic epilepsy")

●Childhood absence epilepsy and juvenile absence epilepsy (see "Childhood absence epilepsy")

●Epilepsy with generalized tonic-clonic seizures alone

●Myoclonic epilepsy of infancy (see "Overview of infantile epilepsy syndromes", section on 'Myoclonic epilepsy in infancy')

●Dravet syndrome (see "Dravet syndrome: Genetics, clinical features, and diagnosis")

●Lennox-Gastaut syndrome (see "Lennox-Gastaut syndrome")

●Lafora disease (see "Hyperkinetic movement disorders in children", section on 'Lafora body disease')

●Unverricht-Lundborg disease (see "Hyperkinetic movement disorders in children", section on 'Unverricht-Lundborg disease')

●Myoclonic epilepsy with ragged-red fibers (MERRF) (see "Mitochondrial myopathies: Clinical features and diagnosis", section on 'MERRF')

●Neuronal ceroid lipofuscinosis, type 2 (CLN2) (see "Neuronal ceroid lipofuscinosis")

DIAGNOSIS

Identifying the provoking stimuli — A detailed clinical history is paramount for revealing whether patients have suspected seizures or symptoms provoked by any of the following visual stimuli [40]:

●Sunlight

●Artificial light (eg, fluorescent or LED lamps)

●Video games

●Watching television

●Specific programs on computer screens

●Striped high-contrast patterns

●Eye closure

Differentiation from psychiatric tics is not always easy [41].

Utility of IPS — For patients with suspected seizures provoked by such visual stimuli, a video-EEG with a standardized intermittent photic stimulation (IPS) protocol is indicated [42,43]. The IPS procedure will provoke epileptiform activity in 90 percent of patients with photosensitivity [20]. The use of a high-quality photic stimulator is important [44]. Testing with a variety of visual stimuli can help to establish or exclude specific sensitivities; it is best to test the specific pattern or video game known from the patient history to induce seizures or symptoms.

Determination of thresholds of IPS-evoked photoparoxysmal response (PPR) by delivering flashes in three separate conditions (at the act of eye closure, with eyes closed, and with eyes open) gives maximal information about the risk of provocation in daily life, without evoking a generalized tonic-clonic seizure in the EEG laboratory [45].

IPS should be stopped immediately if the EEG shows generalized epileptiform discharges in order to reduce the risk of a seizure during the procedure [20].

Utility of video-EEG — Close observation with video-EEG recording will reveal minor ictal symptoms or signs during a PPR in approximately 70 percent of patients. The majority will be eyelid myoclonia and myoclonus of neck and arms; approximately one-quarter will involve brief loss of consciousness, blurred vision, dizziness, and/or nausea [46]. These clinical signs help to classify the epilepsy (generalized or focal) and to inform the patient about what signs and symptoms are connected with their photosensitivity. This knowledge also helps them to detect and prevent potentially provocative situations.

When Sunflower syndrome is suspected, long-term video-EEG recording is indicated with the patient in a "sunny" environment; daylight is necessary. In clinical practice, it is not easy to distinguish epilepsy with eyelid myoclonia from Sunflower syndrome based upon EEG findings alone (table 1).

MANAGEMENT

Nonpharmacologic — In general, management of photosensitivity involves avoidance of provoking factors, use of dark or tinted glasses, watching television or screens in a highly-illuminated room, limiting screen time, and reducing contrast [1,17,24,47]. When unexpectedly exposed to a provoking light stimulus, covering one eye can reduce the likelihood of a seizure, as monocular input reduces the light intensity reaching the eyes by half.

Additional approaches that may be helpful with Sunflower syndrome include wearing hats, staying indoors during sunny days, distraction, and restraining or engaging the hand used in hand-waving [1]. Psychotherapy or behavioral modification may be additional options for patients with Sunflower syndrome and poor seizure control, whereas increased doses of antiseizure medication (ASM) are unlikely to be helpful [35].

In a retrospective study of six patients with epilepsy with eyelid myoclonia (Jeavons syndrome), treatment with the modified Atkins diet, a form of ketogenic dietary therapy, was associated with improved seizure control [48]. All six patients had a >50 percent reduction in seizure frequency, three had a >90 percent reduction in seizure frequency, and one patient became seizure-free. (See "Ketogenic dietary therapies for the treatment of epilepsy", section on 'Modified Atkins diet'.)

Pharmacologic — Some patients with photosensitive epilepsies who do not achieve adequate control with nonpharmacologic measures may respond to treatment with ASM, but high-quality evidence is lacking. Pharmacologic treatment may be particularly useful for patients who are not aware of their seizures and/or provoking visual stimuli and who therefore cannot benefit from nonpharmacologic measures, and for patients with a large range of flash frequency sensitivity (eg, 6 to 50 Hz) who are therefore vulnerable to many different visual stimuli. However, Sunflower syndrome is often drug resistant [49], and many adults have poor adherence [50].

The choice of ASM in photosensitive patients is primarily dependent on the epilepsy syndrome and the patient’s age and sex [51]. Based upon clinical experience and limited observational studies, levetiracetam and valproate (the latter for males) are first-choice ASMs for generalized epilepsies with predominantly myoclonic jerks such as Jeavons syndrome and Sunflower syndrome. Similarly, levetiracetam or valproate are first-choice ASMs for patients with occipital lobe epilepsy [52]. In small observational studies, valproate, levetiracetam, brivaracetam, clobazam, ethosuximide, and lamotrigine have been associated with improved seizure control for patients with reflex epilepsies [6,17,27,53,54]. However, valproate is teratogenic and is generally avoided in females of child-bearing potential.

The treatment of other epilepsy syndromes associated with photosensitivity is reviewed separately:

●(See "Juvenile myoclonic epilepsy", section on 'Treatment'.)

●(See "Dravet syndrome: Management and prognosis".)

●(See "Hyperkinetic movement disorders in children", section on 'Unverricht-Lundborg disease'.)

Although based on limited evidence, many experts avoid phenytoin and, to a lesser extent, carbamazepine and lamotrigine, which may provoke myoclonic jerks in patients with photosensitive seizures [24].

ASM treatment often suppresses the photoparoxysmal response (PPR) reaction to intermittent photic stimulation (IPS), and when withdrawal of medication is considered, the EEG can help in predicting if the photosensitivity is outgrown or not; return of PPR upon ASM withdrawal suggests a higher risk of seizure recurrence.

OUTCOMES — Prognosis is dependent on the type of photosensitive epilepsy.

Photosensitive occipital lobe epilepsy (POLE) tends to have a good prognosis. In a report of 29 patients diagnosed with POLE with five or more years of follow-up, the remission rate was approximately 80 percent [55]. However, despite clinical remission, photosensitivity by EEG persisted in approximately 80 percent, and relapse after clinical remission occurred in over one-half of patients.

In epilepsy with eyelid myoclonia (Jeavons syndrome), seizures are often persistent throughout life, and a substantial number of patients develop drug-resistant epilepsy [56]. In one small study, generalized tonic-clonic seizures and seizure types other than absence seizures were associated with an increased risk of drug-resistant epilepsy [57].

Sunflower syndrome is often associated with lifelong persistent seizures, and more than half of patients have drug resistance [49].

The prognosis of patients with idiopathic generalized epilepsies is reviewed separately for childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. (See "Childhood absence epilepsy", section on 'Prognosis' and "Juvenile myoclonic epilepsy", section on 'Prognosis'.)

The prognosis of patients with developmental and epileptic encephalopathies including Dravet syndrome and Lennox-Gastaut syndrome are also discussed separately. (See "Dravet syndrome: Management and prognosis" and "Lennox-Gastaut syndrome", section on 'Outcomes'.)

Progressive myoclonic epilepsies such as Unverricht-Lundborg and Lafora disease generally have an intractable and catastrophic course. (See "Hyperkinetic movement disorders in children", section on 'Unverricht-Lundborg disease' and "Hyperkinetic movement disorders in children", section on 'Lafora body disease'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in children" and "Society guideline links: Seizures and epilepsy in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Seizures (The Basics)" and "Patient education: Epilepsy in adults (The Basics)" and "Patient education: Epilepsy in children (The Basics)")

●Beyond the Basics topics (see "Patient education: Seizures in children (Beyond the Basics)" and "Patient education: Seizures in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Photosensitive epilepsies – Photosensitive epilepsies constitute a heterogeneous group of reflex epilepsies that are triggered by visual stimuli. (See 'Introduction' above.)

●Pathophysiology – Patients exhibit a photoparoxysmal response (PPR) (epileptiform activity on EEG) provoked by intermittent photic stimulation (IPS). The provoking visual features in patients with photosensitive epilepsy are related to flash frequency, intensity, duration, retinal coverage, and particular patterns and colors. (See 'Pathophysiology' above.)

●Epidemiology – Photosensitive epilepsies together are the most common type of reflex epilepsy. (See 'Epidemiology' above.)

●Clinical features – Onset is usually in the first decade of life. The clinical features vary by phenotype:

•Photosensitive occipital lobe epilepsy – Seizures are precipitated by light stimulation, particularly video games or television. The seizures are typically focal, consisting of visual blurring, hallucinations, or blindness, lasting for approximately a minute, and in some cases progressing to generalized tonic-clonic seizures. (See 'Photosensitive occipital lobe epilepsy' above.)

•Epilepsy with eyelid myoclonia (Jeavons syndrome) – This is a genetic generalized epilepsy. Seizures are provoked by eye closure. Seizures are characterized most often by eyelid myoclonia, absences, and less often with generalized tonic-clonic seizures. (See 'Epilepsy with eyelid myoclonia (Jeavons syndrome)' above.)

•Sunflower syndrome – This syndrome is characterized by heliotropism (a compulsive attraction to sun or light) and stereotyped seizures (table 1). Patients typically present with hand-waving episodes, described as turning toward the sun, and waving one hand in front of their eyes; hand-waving may be a manifestation of seizure activity, a method of seizure self-induction, or both. Other seizure types include absence, eyelid myoclonia, and/or generalized tonic-clonic seizures. (See 'Sunflower syndrome' above.)

Photosensitivity is also a common feature in many generalized epilepsy syndromes (eg, childhood absence epilepsy, Lennox-Gastaut syndrome, and many others), as listed above. (See 'Idiopathic and genetic epilepsy syndromes' above.)

●Diagnosis – A detailed clinical history is needed to determine if patients have seizures provoked by visual stimuli such as sunlight, artificial light, television, video games, striped high-contrast patterns, or eye closure. A video-EEG with a standardized IPS protocol is indicated to confirm photosensitivity and classify the epilepsy. (See 'Diagnosis' above.)

●Management – In general, management of photosensitivity involves avoidance of provoking factors, use of dark or tinted glasses, watching television or screens in a highly illuminated room, limiting screen time, and reducing contrast. Some patients who do not achieve adequate control with nonpharmacologic measures may respond to antiseizure medication such as levetiracetam or valproate, but valproate is teratogenic and is generally avoided in females. (See 'Management' above.)

●Outcomes – Photosensitive occipital lobe epilepsy tends to have a high remission rate, but many patients will have a relapse. Seizures with Jeavons syndrome and Sunflower syndrome are typically persistent and drug resistant. (See 'Outcomes' above.)