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Keywords:

  • Electronic screen game–induced seizure (ESGS);
  • Photosensitivity;
  • Pattern-reversal stimulation;
  • Intermittent photic stimulation;
  • Visual perception

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Summary:  Purpose: With the ever-increasing popularity of computers, electronic screen game–induced seizure (ESGS) is beginning to pose a serious social problem. To elucidate the pathophysiology of ESGS, with the ultimate goal of prevention, we have been studying photo-pattern sensitivity in detail with a pattern-stimulation test using a CRT (cathode ray tube) display. This method is referred to as the “CRT-pattern test.”

Methods: We studied 17 patients brought to our department for evaluation of ESGS. EEG responses were recorded during exposure to various patterns consisting of three elements: spatial resolution, brightness perception, and pattern-movement recognition displayed on a CRT monitor. Photo-paroxysmal response (PPR) frequencies were compiled for each stimulation.

Results: PPR was induced by the CRT-pattern test in nine of the 17 cases. In four cases, PPR induction was obtained only after introducing CRT-pattern tests in addition to standard intermittent photic stimulation (IPS). The rate of PPR induction differed according to the type of pattern, spatial frequency, and pattern-reversal frequency. However, neither the clarity of the edges of a pattern nor changes in the brightness of a pattern element had any effect on the rate of PPR induction. With the exception of a few subjects, the stimulation caused by pattern movement was not effective in eliciting PPR. Six cases in whom spatial resolution was involved showed occipital dominance in PPR provocation, and three in whom brightness perception and pattern movement recognition was involved showed frontal dominance.

Conclusions: The CRT-pattern test is useful for identifying patients with photosensitivity among patients considered to have incidental or nonphotosensitive seizures unresponsive to standard IPS. Patients with ESGS caused by photosensitivity can be divided into two groups: those with occipital dominance for PPR provocation, in whom spatial resolution is involved; and another group with frontal dominance, in whom brightness perception and pattern-movement recognition (or possibly perception of colors) are involved.

With the ever-increasing use of computers, it has become impossible to avoid exposure in everyday life. Television games (games that use a television screen to display their images), games using computer screens or portable liquid crystal displays (LCDs), and arcade games using large image displays at so-called game centers are now popular, not only among children but also in adults. In some patients with no seizure history, these epileptic responses develop as isolated incidents. Sudden convulsions provoked by the visual stimulation of staring at these screens, or from stimulation associated with the operation of these screens, constitute not only a medical but also a social problem.

The display, the culprit in the seizure response triggered by playing these games, is not limited to television sets. LCDs and plasma displays, in addition to cathode-ray tubes (CRTs) which are common in home television sets and personal computers, also can be responsible.

The term electronic screen game–induced seizure (ESGS) has now replaced video-game epilepsy (1). There are reports on ESGS unrelated to visual stimulation (i.e., not associated with photo-pattern sensitivity). However, to distinguish these from incidental epileptic episodes, it is essential to obtain electroencephalographic (EEG) recordings while the patient is exposed to intermittent photic stimulation (IPS) and pattern stimulation, as proposed by Harding et al. (2).

For the past 4 years, we have been conducting detailed studies on the photo-pattern sensitivity of patients with ESGS by using a special test (pattern-stimulation test using a CRT display), termed the “CRT-pattern test,” in addition to standard IPS. New perspectives on the pathophysiology and prevention of ESGS have emerged. The details of these insights are discussed.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Subjects

This study on photo-pattern sensitivity was conducted by using a CRT-pattern test on 17 patients brought to our department for medical care. Their seizures during ESG were clinically well defined. The age at onset of ESGS ranged from 8 years and 5 months to 19 years and 2 months (mean, 13 years ± 2 years and 8 months). There were 14 male and three female patients (male/female ratio, 4.7:1).

Before starting all procedures, we fully explained the individual test to the patients and their families, and consent was obtained.

Methods

The standard EEG test, complemented by IPS, hyperventilation, and sleep, was initially performed. Before and after the CRT-pattern test, a photo-pattern stimulation test using a strobe light (i.e., the “strobe-pattern test”) also was conducted on seven patients. The CRT-pattern test and the strobe-pattern test were conducted on separate days.

The subjects were divided into two groups according to PPR-positivity by the CRT-pattern test, and then clinical backgrounds and EEG and seizure findings were compared between these two groups.

CRT-pattern test

Various patterns that had been prepared on a computer (described later) were displayed on a 21-inch multi-monitor (Iiyama, MT-8521E, Japan), and EEG responses were recorded simultaneously. The monitor screen has interlaced scanning lines with a flickering component of 60 Hz and 30 frames/s. The baseline conditions were a sitting posture, 1 m distance between the monitor and the test subject, and a dark environment. The test was conducted during the day, with the patient fully awake after adequate sleep.

The elements of the patterns used for stimulation were divided and tested in the following sequence: (a) spatial resolution, (b) brightness perception, and (c) pattern-movement recognition. For the first two elements, a pattern-reversal stimulation method was used, and each pattern was displayed for 10 s at 10-s intervals at pattern-reversal frequencies of 5, 10, 20, and 30 Hz.

Spatial resolution.

The patterns used for the study of spatial resolution consisted of (a) vertical stripes, (b) horizontal stripes, (c) checkered patterns, (d) grid patterns, and (e) concentric circles.

For a comparative evaluation, well-defined patterns (a border consisting of square waves) and not so well defined patterns (a border consisting of sine waves) were prepared (Fig. 1). The first pattern used square waves with two levels of brightness (0 and 100%) for a periodic function contrasting the dark and light tones. For the second pattern, sine waves were used as the periodic coefficient [brightness = a* sin(x) × b* sin (y), where a* and b* are constants required by spatial frequencies], for a smooth transition from darkness to brightness.

image

Figure 1. Patterns used to study edge effects and spatial resolution. On the left, the border is marked by a sine-wave pattern and is poorly defined; the pattern on the right shows a clear square-wave border. Increasing the spacial frequency produces finer patterns. Spatial frequency of patterns on the right is the double of left ones.

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The size of each pattern was varied to achieve three levels during the test (spatial frequencies at 1.0, 2.0, and 4.0 cpd).

Brightness perception.

To evaluate brightness perception, checkered patterns—a pattern in yellow and blue, complementary to yellow with limited brightness change, and one in yellow and black with an exaggerated brightness change—were used (Fig. 2). The size of these checkered patterns was varied to achieve three levels during the test (spatial frequencies at 1.0, 2.0, and 4.0 cpd.)

image

Figure 2. Patterns used to study sensitivity to changes in the brightness. The left checkered pattern of yellow and blue that is complementary to yellow has been prepared to minimize change in the brightness. The right yellow-and-black checkered pattern has been prepared as a combination, maximizing change in the brightness.

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Pattern-movement recognition.

For the study of movement recognition, patterns composed of fine line segments and circles were used. The line segments were moved in four directions (horizontally and vertically) at five speeds (3, 6, 12, 24, and 48 deg/s), whereas the circles were moved in two directions (centripetally and centrifugally) at five speeds (1, 2, 4, 8, and 16 deg/s). Each pattern was moved for 10 s at 10-s intervals for stimulation.

Each test procedure required ∼70 min (including a 5-min rest period). In each procedure, EEG signs of PPR were monitored, and the stimulation was immediately interrupted if a sign was recognized. The succeeding stimulation was resumed only after EEG recovery had been confirmed. The development of diffuse spike-and-wave complexes was taken as a sign of PPR provocation (type 4 of the Waltz classification) (3). When the amplitudes of these spike-and-wave complexes were focally exaggerated despite the EEG pattern being diffuse, or the spike-and-wave complexes locally preceded the diffuse pattern, the particular brain region was designated as PPR-dominant (Fig. 3). When spike-and-wave complexes were localized (type 2 or 3 of the Waltz classification) rather than generalized, a designation of probable PPR-positivity was assigned.

imageimage

Figure 3. An example of photo-paroxysmal response (PPR) provocation. A: Frontal dominance; it represents diffuse PPR, but the amplitude of spike-and-wave complexes is exaggerated focally at the frontal region. B: Occipital dominance; PPR is diffuse, but it was preceded by spike-and-wave complexes that were localized at the occipital region but later became diffuse.

To evaluate the effects of spatial frequencies (fineness of the patterns), pattern border definition, pattern types, changes in the brightness of pattern elements, and pattern-reversal frequencies on PPR provocation, PPR frequencies were compiled for each stimulation in a single test subject. The localized spike-and-wave complexes were added to the compilation, with each being counted as 0.5.

The actual procedure by which stimuli were presented was as follows. To compare spatial frequencies, patients were exposed to 48 stimuli, which consisted of five patterns, with two border patterns each, and two checkered patterns (5 × 2 + 2 = 12), with four different pattern-reversal frequencies (12 × 4 = 48). To compare the influences of pattern border definition, patients were exposed to 60 stimuli consisting of five patterns with four different pattern-reversal frequencies each, presented with three spatial frequencies (5 × 4 × 3 = 60). When we compared the pattern types, patients were exposed to 24 stimuli consisting of two different border patterns with four pattern-reversal frequencies each, again presented with three spatial frequencies (2 × 4 × 3 = 24). In an evaluation of brightness perception, patients were exposed to 12 stimuli consisting of a checkered pattern, with four pattern-reversal frequencies, presented with three spatial frequencies (1 × 4 × 3 = 12). To evaluate PPR induction by different pattern-reversal frequencies in the spatial resolution and brightness-perception tests, patients were exposed to 36 stimuli [i.e., five patterns with two border patterns each, and two checkered patterns (5 × 2 + 2 = 12), all presented with three spatial frequencies (12 × 3 = 36)].

The data were expressed as means ± standard deviation. The Student t test was used to compare the frequencies of provoked PPR and localized spike-and-wave complexes among PPR-positive patients. The statistical significance was set at p < 0.05 for the two-tailed test.

Strobe-pattern test

In addition to the standard white IPS, various filters that produce impressions of a deep red color (>600 nm, stimulates only red cones), polka dots, and oblique line patterns (Nihon Kohden R-11, DU-12, GO-12), were mounted on the front part of a flicker device (Nihon Kohden lamp, LS-703A, 0.6J) at a distance of 30 cm from the eye, as described by Takahashi et al. (4–6). The flicker frequency was set at 3–30 Hz. Each stimulation was delivered at 10-s intervals and lasted for 10 s.

Stimulation with white light also was evaluated under the following three ocular conditions: (a) with the eyes closed (kept closed during flicker stimulation); (b) with the eyes open (kept open during flicker stimulation); and (c) with eyes open or closed (with the eyes closed when the flicker stimulation was started, open during the test, and closed again during stimulation). Reactions also were observed while the subjects gazed for 10 s at patterns produced by polka-dot and oblique-design filters located at a distance of 30 cm from the eye. The following sequence was used for these tests: white flickering light (eyes open or closed, open, and then closed); red flickering light, flickering polka dots, flickering oblique line, and pattern gazing. The flicker stimulation were set at 3, 6, 8, 10, 12, 14, 16, 18, 20, 21, 24, 27, and 30 Hz. Preliminary practice was necessary to prompt the test subjects to open or close their eyes during flicker stimulation. For practice, the subjects were instructed to open and close their eyes several times without stimuli, after which a series of tests was conducted. This necessitated the sequence given earlier.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Clinical background, ESGS manifestations and their precipitating factors in the 17 patients (Table 1, 2)

Table 1. Clinical backgrounds and ESGS manifestations
CaseAge (onset)Age (exam)SexFamily Hx.Past Hx.ACD (onset)ACD (exam)IQSz. typePlay timeFeverSleep deprivationHunger
  1. NF-1, neurofibromatosis type 1; PS, photosensitivity; HD, hemodialysis; O.C., Hx of ordinary class; FC, febrile convulsion; PB, phenobarbital; CBZ, carbamazepine; PHT, phenytoin; VPA, valproic acid; GTCS, generalized tonic–clonic seizure; 2nd, secondarily; CPS, complex partial seizure.

114y5m14y5mMFCFC, Epi1142nd GTCS1.5 h
212y7m12y11mMFC 83GTCS20 min?
313y5m13y6mMEpi(PS+)O.C.GTCS10 min+?
410y0m10y2mFFCFCO.C.GTCS30 min+
5 8y5m 9y5mFEpi 962nd GTCS30 min?
614y1m14y6mFNephritis(HD)O.C.GTCS1.5 h?
7 8y10m 9y2mMNF-1NF-1, aFCVPA1072nd GTCS2 h?
815y1m15y2mMVPAO.C.GTCS1 h++
919y2m20y11mMFCFC, EpiVPA 582nd GTCS?
1014y4m14y9mMFC, aFC116GTCS?++
1113y3m16y5mMEpiPBPBO.C.2nd GTCS3.5 h+?
1214y4m16y2mMO.C.GTCS?+?
1314y1m14y8mMFC, EpiCBZCBZ 782nd GTCS??
1412y9m16y5mMFCVPA 82CPS???
15 9y6m22y4mMVPAO.C.GTCS???
1614y0m16y9mMEpiPBVPA 98GTCS???
1712y4m14y6mMFCFC, EpiPHTVPA113CPS?+?
Table 2. EEG, seizure findings, and precipitating factors
CaseEEG findingsSeizure frequencyMonitorCategory of ESG
ESGSOther than ESGSpontaneous (Pre.) Exam
IPS (Pre.)Awake/ SleepIPSStrobe patternCRT pattern
  • IPS, intermittent photic stimulation; CRT, cathode ray tube; ESGS, electronic screen game–induced seizure; (Pre.), previously; NE, not examined; N, normal; A, abnormal; J.C., Japanese chess; Sun., sunlight; Com., computer; Fig., small figure; S, simulation; A, action; R, role-playing game; P, puzzle.

  • a

     Receiving valproic acid.

1(N)A/ANNA10(2) —Com. (CRT)S
2(NE)N/ANAA10(0) —TV (CRT)A
3(NE)N/AANEA10(0) —TV (CRT)R
4(NE)A/NANEA10(0) —Handheld (LCD)P
5(NE)N/AAAA10(0) —TV (CRT)P
6(NE)A/AAAA10(0) —Handheld (LCD)P
7(NE)N/AaNaNaAa10(1) —Handheld (LCD)?
8(NE)A/AaNaNEaAa11 (J.C.)(0) —TV (CRT)R
9(A)N/NaAaNEaAa11 (TV)(10<) —TV (CRT)A
10(NE)N/NNNN10(2) +Arcade (CRT)A
11(N)N/NNNEN20(3) —TV (CRT)A
          /Handheld (LCD)R
12(NE)N/NNNEN40(0) —TV (CRT)A
13(N)N/ANNEN12 (TV)(10<) +TV (CRT)?
14(N)N/NaNaNEaNa10(5) +Handheld (LCD)?
15(A)N/NaNaNaNa32 (Sun.)(2) —TV (CRT)?
16(A)N/NEaNEaNEaNa11 (IPS)(3) —Arcade (CRT)?
17(A)N/NaNaNEaNa510< (Sun. TV(10<) —TV (CRT)A
        /Com. Fig.)  /Handheld (LCD)?

Based on medical history, an ESGS seizure type was tentatively assigned to each case as follows: generalized tonic–clonic seizure, nine cases (53%); secondarily generalized seizure, six (35%); and complex partial seizure, two (12%). Thus a focal seizure origin was suggested in about half of the cases.

The time span from the start of the game to the onset of the seizure, which was confirmed in 11 cases, ranged from 10 min to 3.5 h, with a mean of 1.2 h.

Among possible provocative factors, sleep deprivation was confirmed in seven (78%) of the nine and hunger in two (20%) of the 10 questioned. In addition, two (cases 7, 16) reported a headache before onset.

The culprit monitors were predominantly television screens (10 cases, 59%), followed by portable LCDs (6), arcade games (2), and a computer display (1). Thirteen kinds of game software (action, six; puzzles, three; role-playing games, three; and simulation, one) were identified in 12 cases.

Clinical analysis based on the results of CRT-pattern tests

Details of patients with positive CRT-pattern test results

A positive CRT-pattern test was recognized in nine (53%) (cases 1–9) of the 17 subjects tested. AEDs were not administered in cases 1–6, whereas valproate (VPA) was initiated in cases 7–9 (Tables 1 and 2).

Case 1.

A 14-year, 5-month-old boy showed no response to IPS or the strobe-pattern test. He experienced two spontaneous seizures before the onset of ESGS that developed during a simulation game displayed on the computer monitor.

Case 2.

A 12-year, 7-month-old boy exhibited no response to IPS, but the strobe-pattern test was positive. He experienced only one episode of ESGS, during an action game displayed on the TV monitor, and no spontaneous seizures.

Case 3.

A 13-year, 5-month-old boy had a positive response to IPS. He did not have spontaneous seizures, but one episode of ESGS occurred during a role-playing game displayed on the TV monitor.

Case 4.

A 10-year-old girl showed a positive IPS response. She had no spontaneous seizures, but did experience one episode of ESGS during a puzzle game displayed on the handheld LCD monitor.

Case 5.

An 8-year, 5-month-old girl exhibited positive IPS and strobe-pattern test responses. She experienced one episode of ESGS while a puzzle game was displayed on the TV monitor, but no spontaneous seizures.

Case 6.

A 14-year, 1-month-old girl demonstrated positive IPS and strobe-pattern test responses. She had only one episode of ESGS while a puzzle game was displayed on the handheld LCD monitor, but no spontaneous seizures.

Case 7.

An 8-year, 10-month-old boy showed no response to either IPS or the strobe-pattern test. He experienced one spontaneous seizure and another episode of ESGS while a game was displayed on the handheld LCD monitor.

Case 8.

A 15-year, 1-month-old boy exhibited no response to IPS. He had no spontaneous seizures, but did experience one episode of ESGS while a role-playing game was displayed on the TV monitor, as well as another seizure provoked by a Japanese chess game.

Case 9.

A 19-year, 2-month-old man demonstrated a positive response to IPS. He had experienced >10 spontaneous seizures before the onset of ESGS, which developed during display of an action game on the TV monitor. He had a history of another seizure provoked by TV viewing.

None of these nine patients, even the four with positive CRT-pattern and negative IPS tests, showed occipital spikes on the EEG even during stimulation.

Comparison of clinical backgrounds between PPR-positive and PPR-negative cases by CRT-pattern test

Among the nine PPR-positive patients (cases 1–9), four (44%) had a history of convulsive episodes, and six (67%) had a family history of convulsions. None had been taking AEDs before the onset of ESGS. At the time the test was administered, three (33%) were being treated with VPA. One of five patients who underwent IQ testing showed a borderline intellectual disability. Those not given an IQ test had performed adequately in regular schools (Table 1).

The eight patients in whom there was no proof of PPR were all boys (cases 10–17). Convulsive episodes had been experienced by five (63%) and had occurred in family member(s) of two (25%). AEDs were being used by four (50%) at the onset of ESGS and by six (75%) at the time of testing. Four (50%) children had taken VPA since the onset of ESGS. None exhibited evident retardation.

Comparison of EEG and seizure findings between PPR-positive and PPR-negative cases by CRT-pattern test

Among the nine PPR-positive cases, two had undergone EEG testing before this study, and one (case 9) was found to be PPR positive by conventional IPS. On the EEG obtained in the present test, paroxysmal abnormal discharge was noted in four (44%) while awakening and in seven (78%) during sleep. Photo-pattern sensitivity was discovered for the first time by this CRT-pattern test in four (44%) with negative responses to conventional IPS. Two (cases 1 and 7) of the four patients also had negative reactions on the strobe-pattern test. Two (cases 7 and 8) of three patients (cases 7, 8, and 9) who were already being treated with VPA at the time of testing showed negative PPR to conventional IPS but positive reactions to the CRT-pattern test used herein (Table 2).

The strobe-pattern test produced positive PPR in three cases. PPR was provoked by white flickering light stimulation (eyes open and closed) in case 2, by either white flickering light (eyes open or closed) or flickering polka dots–oblique line stimulation in case 5, and by white flickering light stimulation (eyes open or closed) in case 6.

ESGS was provoked only once during this study in each patient, and seizure was provoked by stimuli other than ESG only once in two patients [television viewing and shogi (Japanese chess game) playing]. Two of the three patients with a history of spontaneous seizures had experienced these attacks no more than twice. On the other hand, the remaining six had never had a seizure episode before the onset of ESGS.

Among the eight patients without PPR on the CRT-pattern test, six had undergone EEG tests before this study and three (cases 15, 16, and 17) showed a positive PPR to conventional IPS. The EEG conducted during the present study showed no paroxysmal abnormal discharges in any subjects during awakening and in only one of the seven while asleep. The PPR was negative in all seven who underwent conventional IPS and in two who were given the strobe-pattern test. At the time of the CRT-pattern test, four patients had experienced ESGS only once. The remaining four had had multiple experiences. The frequency of seizures caused by stimuli other than ESG was once in one and multiple times in the remaining three. These stimuli included sparkling sunlight, television viewing, operating personal computers, staring at books with small geometric figures, and IPS used in normal EEG tests. Five patients (the majority) had experienced spontaneous seizures (with no obvious provocation) more than 3 times, whereas one patient without a history of spontaneous seizure experienced four seizures that were all classified as ESGS. Three patients (cases 10, 13, and 14) had repeated spontaneous seizures between the onset of ESGS and the start of the CRT-pattern test.

PPR induction by CRT-pattern test

Spatial resolution
Comparing spatial frequencies.

PPR was more frequently induced in all nine patients when they were exposed to finer patterns (2.0 cpd or more). Specifically, the frequencies of PPR and localized spike-and-wave complexes after 48 stimuli delivered with three different spatial frequencies were compiled for each individual, and the means were 1.9 ± 3.3 for 1.0 cpd; 6.1 ± 7.2 for 2.0 cpd; and 8.2 ± 6.6 for 4.0 cpd. Statistically significant differences were noted between stimuli of 4.0 or 2.0 cpd versus 1.0 cpd (p = 0.01 and p = 0.03) (Tables 3 and 4, and Fig. 4).

Table 3. Photo-paroxysmal response induction by pattern-reversal stimuli
CaseSpatial frequency (cpd)Definition of pattern bordersChanges in brightnessPattern-reversal frequency (Hz)Pattern types
1.02.04.0sinesquareY–BlueY–Black5102030VHChGCo
  1. V, vertical stripe; H, horizontal stripe; Ch, checkered pattern; G, grid pattern; Co, concentric circle.

10.517.536001.51.53363000
28.521.51423.520.52.5371411127.5118.51.515.5
308.517.5131300178101010006
404.51068.51012.53.57.57.530.503.5
50.58.587100016.53.568.51.5205
60000003000000000
771115151813.58.57116.51194.54.54
80000001000000000
9101.51.51000.510.50.500.5200
Mean1.96.18.27.78.60.51.22.34.44.55.15.64.21.90.73.8
SD3.37.26.68.07.60.91.53.24.64.44.44.44.52.91.55.0
Table 4. Evaluation of the anatomic sites favoring the development of photo-paroxysmal response
CaseSpatial resolution PPR inductionBrightness-perception PPR inductionMovement-recognition PPRAnatomic sites
Spatial frequencyPattern typesY–Blue vs. Y–Black
11.0 ≪ 4.0G ≪ VP-O
21.0 ≪ 2.0G ≪ HY–Blue ≦ Y–BlackP-O
31.0 ≪ 2.0G ≪ VO
41.0 ≪ 4.0G ≪ VT–Blue > Y–BlackO
51.0 ≪ 2.0G ≪ VO
6Y–Black only+F
7Y–Blue ≪ Y–Black+F
8Y–Black onlyF
9P-O
 P-interblobHighLowLow  
 P-blobLowHighLow  
 Magno.LowHighHigh  
image

Figure 4. Photo-paroxymal response induction by pattern-reversal stimulation. *p < 0.05.

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Next, the number of patients among the nine with PPR was tabulated. At 1.0 cpd, only three produced definitive positive reactions: 2.0 and 4.0 cpd elicited positive responses in six and seven patients, respectively.

Comparing pattern border definition.

Patterns with clearer borders appeared to be more likely to provoke PPR, but the difference was not significant. When the frequencies of PPR and localized spike-and-wave complexes after 60 stimuli delivered with two distinct pattern borders each were compiled for each individual, the mean for patterns with an ambiguous outline (border defined by sine waves) was 7.7 ± 8.0. For patterns with a clearer outline (border defined by square waves), it was 8.6 ± 7.6, with no statistically significant difference between the two (p = 0.24).

Comparing pattern types on PPR provocation.

Vertical and horizontal stripe patterns were found to be more likely to provoke PPR than were grid patterns. The frequencies of PPR and localized spike-and-wave complexes after 24 stimuli delivered with five different pattern types were compiled for each individual. The means were 5.6 ± 4.4 for vertical stripes, 4.2 ± 4.5 for horizontal stripes, 3.8 ± 5.0 for concentric circles, 1.9 ± 2.9 for checkered patterns, and 0.7 ± 1.5 for grid patterns. Significant differences were noted between the vertical or horizontal stripes and the grid patterns (p = 0.01 and p = 0.02, respectively). A significant difference also was noted between the vertical stripes and the checkered patterns (p = 0.04).

Next, the number of patients developing PPR was tabulated: those developing definite PPR with the stimulation of observing vertical stripes, horizontal stripes, checkered patterns, grid patterns, and concentric circles were 6, 6, 4, 2, and 5, respectively.

Brightness perception

The changes in the brightness of pattern elements were compared. There was no difference in the incidence of PPR caused by stimulation with a yellow–blue checkered pattern versus a yellow–black checkered pattern. When the frequencies of PPR and localized spike-and-wave complexes after 12 stimuli delivered with two different brightness changes each were compiled for each individual and a mean was computed; with the yellow–blue checkered pattern it was 0.5 ± 0.9; and with the yellow–black checkered pattern, 1.2 ± 1.5. There was no statistically significant difference between the two (p = 0.16).

Pattern movement recognition

Stimulation caused by moving the patterns provoked PPR or localized spike-and-wave complexes in only two of the nine test subjects. Specifically, case 7 developed PPR once when the line section moved from left to right (6 deg/s); and case 6 developed localized spike-and-wave complexes 10 times when exposed to the following stimuli: a line section moving from left to right (3, 12, and 24 deg/s), a line section moving from right to left (3 and 48 deg/s), a circle collapsing centripetally (4, 8, and 16 deg/s), and a circle expanding centrifugally (4 and 16 deg/s). PPR or localized spike-and-wave complexes are more likely to develop when stimuli move more quickly, but the number of reacting individuals was too small to allow a meaningful statistical evaluation.

PPR induction by different pattern-reversal frequencies in the spatial resolution and brightness-perception tests

Pattern-reversal frequency in a range of 10 to 30 Hz was highly effective in provoking PPR. The frequencies of PPR and localized spike-and-wave complexes after 36 stimuli delivered with four different pattern-reversal frequencies were compiled for each individual. The means were 2.3 ± 3.2 for 5 Hz, 4.4 ± 4.6 for 10 Hz, 4.5 ± 4.4 for 20 Hz, and 5.1 ± 4.4 for 30 Hz. There was a tendency for the PPR and localized spike-and-wave complexes to be provoked more frequently with pattern-reversal stimulation at ≥10 Hz, but the variation among individuals was too great, such that statistically significant differences were noted only between 20 and 5 Hz (p = 0.07 between 10 and 5 Hz, p = 0.02 between 20 and 5 Hz, and p = 0.05 between 30 and 5 Hz).

Next, the number of patients developing PPR was tabulated. At 10 Hz, seven were PPR positive; and six had positive reactions at 5, 20, and 30 Hz.

Evaluation of anatomic sites favoring the development of PPR

The nine individuals who developed PPR during the CRT-pattern test were roughly divided, according to PPR dominance, into two groups: one showed occipital dominance and comprised the majority of patients (cases 1–5 and 9), the other showed frontal dominance and represented one third of the patients (cases 6, 7, and 8). Some differences in their reactions to the CRT-pattern test were observed. Among the cases with frontal dominance, for example, the yellow–black stimulus with greater brightness change, in comparison with the yellow–blue stimulus with limited change in brightness, provoked PPR or localized spike-and-wave complexes much more frequently in two patients (cases 6 and 7). When the patterns were compared, PPR was provoked only by the yellow–black checkered pattern in two cases (cases 6 and 8). Pattern movements provoked PPR or localized spike-and-wave complexes in only two cases (cases 6 and 7), both belonging to the frontal dominance group (Tables 3 and 4).

The incidences of the development of PPR and localized spike-and-wave complexes, in association with spatial frequency, were tabulated individually for the six patients in the occipital dominance group. The incidence was significantly higher at 2.0 or 4.0 cpd than at 1.0 cpd, in all but one case. The incidence of provocation by pattern type also was investigated in the same subjects. The incidence was found to be significantly elevated by exposure to vertical or horizontal stripe patterns in comparison with the grid pattern.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Causes and definition of ESGS

ESGS was first reported by Rushton and Ferry, who coined the term, “video-game epilepsy”(7,8). With the subsequent rapid dissemination of these games, increasing numbers of studies have been conducted, but the definition of ESGS has not yet been established.

No clear definition is given even in the Consensus Statement prepared by the Video-Game Epilepsy Consensus Group, which was published in 1994. The statement merely introduces the following as its causes (9): (a) a photosensitive response to the physical characteristics of a television display, i.e.; (b) a photosensitive response to the visual content of the game; (c) seizure precipitation by specific cognitive activities, decision making, hand movements, etc.; (d) seizure precipitation by nonspecific emotional factors relating to the subject's engagement in the game, such as anxiety or excitement; (e) lowering of seizure threshold by fatigue or sleep deprivation; and (f) chance occurrence of a spontaneous seizure in a person with epilepsy playing a video-game.

Accordingly, if ESGS is defined as any seizure activity that develops when one plays a video game, it may include even those that incidentally occur while playing such a game.

For the diagnosis of an epileptic seizure provoked while playing a video game, William et al. (10) emphasized the following: (a) the repeated occurrence of seizures during video games; (b) a history of previous epileptic manifestations triggered by other visual stimuli; and (c) laboratory demonstration of EEG paroxysmal responses to a variety of visual excitations, including actual video-game playing, stroboscopic stimulation, and presentation of line patterns.

Identification of photo-pattern–sensitive individuals

Based on the theories described earlier, we studied 17 patients with ESGS. Among them, three (cases 10, 13, and 14) experienced repeated spontaneous non-ESGS seizures between the onset of ESGS and the CRT-pattern test, raising the possibility that their ESGS was incidental. Fourteen others did not experience a spontaneous seizure during this period: nine (cases 1–9) were PPR-positive on the CRT-pattern test, and photosensitivity had already been proved in three of the remaining five (cases 15, 16, and 17). VPA has been shown to be the most effective agent for the treatment of photosensitivity (11). The three patients taking VPA were PPR-positive on the previous conventional IPS test before the introduction of VPA, but PPR-negative on the CRT-pattern test after the initiation of this treatment. It is plausible that these 12 patients (cases 1–9, and 15, 16, and 17) represent ESGS caused by photo-pattern sensitivity. The remaining two (cases 11 and 12) were PPR-negative, had no history of spontaneous seizures other than ESGS, and experienced repeated ESGS. Therefore, it is highly likely that in these cases, ESGS were induced by a factor other than photo-pattern sensitivity.

In a survey conducted by Quirk et al. (1) throughout England, and based on EEGs and other findings, it was believed that 47 (40%) of 118 patients who experienced ESGS for the first time represented incidental seizures. In the same survey, incidental seizures were defined as those in which there was no PPR provocation and they were not classified as types 1 through 4, according to Waltz et al. (3); those with no subsequent occurrence of other photic-induced seizures or no occurrence of seizures in association with playing ESGs with subsequent exposure; and those with no occipital epileptiform discharges in the resting EEG. Only two patients (12%, cases 10 and 14) in the present study matched these descriptions. Conversely, 64 (54%) patients in the survey by Quirk et al. were judged to represent the condition in which photosensitivity was involved in the pathogenesis of ESGS. Their study was community based and restricted to patients with a first seizure while playing ESGs. In contrast, our study is hospital based, including not only the patients experiencing their first seizure but also patients with two or more seizures. A simple comparison was believed to be inadequate, but in the present study, 13 (76%) patients were placed in this category—the aforementioned 12 in whom photo-pattern sensitivity was presumably the cause of their seizures; and one (case 13) in whom photo-pattern sensitivity was not confirmed but who had a history of seizures provoked by visual stimulation other than ESGs.

The present study was extended to identify a diagnostic test that would be suitable for detecting PPR positivity. The four patients with negative responses to conventional IPS reacted positively to the CRT-pattern test used in this study. Specifically, cases 1 and 7 showed no response to either IPS or the strobe-pattern test, but both were PPR positive on the CRT-pattern test. Case 2 showed a negative response to IPS but responded positively to the strobe-pattern test and the conditions of the CRT-pattern test. Case 8, who did not undergo strobe-pattern testing, reacted negatively to IPS but showed a positive response to the CRT-pattern test. Moreover, cases 7 and 8 responded positively to the CRT-pattern test even while receiving VPA treatment. These observations indicated that all four patients had only pattern sensitivity (i.e., not photosensitivity), or that the CRT-pattern test, followed by the strobe-pattern test, and finally the IPS test, was useful for detecting PPR-positivity. In Japan, the Nihon-Kohden photic stimulator is the most common means of delivering IPS. Although we did not compare the PPR-eliciting effectiveness of this device with those of other stimulators, such as the Grass and Nihon-Kohden types, or the former and the CRT monitor, the present results suggest the CRT-pattern test to be more useful than the conventional IPS test. Thus, by introducing special stimulation tests (such as the CRT-pattern test), it may be possible to discover patients with photo-pattern sensitivity among those who have been considered to represent incidental seizure or nonphotosensitive seizure, based on the results of conventional IPS testing.

There has been a paucity of reports on the incidence of ESGS not caused by photosensitivity. According to the survey by Quirk et al. (1), seven (6%) patients had recurrent seizures on repeated exposure to ESGs without electroclinical evidence of photosensitivity. By introducing this special stimulation test, it may be possible to obtain more accurate data on this incidence. In this study, the incidence of non-photosensitive ESGS was 12% (two of the 17 cases).

Pathophysiology of ESGS

In this study, pattern stimulation provided by the CRT-pattern test was divided according to three elements, spatial resolution, brightness perception, and pattern-movement recognition. These three elements are examined when processing information on visual perception. According to Livingstone and Hubel (12), the visual information-processing pathway, which begins at the retinal level and reaches the cerebral cortex—including the primary and succeeding fields of visual perception—can be roughly divided into two parts, each of which is involved in selective information-processing tasks.

The first is the P-cell pathway represented by the parvocellular layers of the lateral geniculate body. It receives information projected from the small cells of the retina and ends at the 4Cβ layer of the primary visual field. This pathway then divides, and the information is transmitted to blobs, which exist in layers 2 and 3, and are darkly stained by cytochrome oxidase (CO), or to an interblob. From the blobs, the information is further transmitted to the CO-positive thin stria of the secondary visual field, and then to the higher V4 field, which is involved mainly in processing color perception (partly for brightness and form). From the interblob, information is projected to the CO-negative sections between the stria of the secondary visual field, and then probably to the V4 field, which is involved mainly in processing information on form and its edges.

The second is the M-cell pathway represented by magnocellular layers of the lateral geniculate body. It receives information projected from the large cells of the retina and ends at the 4Cα layer of the primary visual field. From there, the information is transmitted directly to the higher MT area (middle temporal area) through the 4B layer; or it is projected from the 4B layer to the MT area through the CO-positive thick-stria section of the secondary visual field. The MT area is involved in processing information concerning form, movement, and stereoscopic characteristics.

Processing through the blobs in the P-cell system excels in color selectivity and brightness perception but is inferior in spatial resolution or speed perception. The pathway through the interblobs is color selective and outstanding in spatial resolution but is less sensitive in brightness perception or speed perception. The M-cell pathway, on the other hand, excels in brightness perception or speed perception; but it lacks color selectivity and is inferior in spatial resolution (Table 4).

In an isoluminescence test for the study of visual perception, the M-cell pathway, which transmits information on differences in brightness including distance perception, stereoscopic view, and perception of pattern movements, is ineffective when patterns of equal brightness are compared. In a test designed to recognize fine patterns with high spatial frequencies, perception by the M-cell pathway or the P-cell pathway, especially via blobs, which are inferior in spatial resolution, become invalid (i.e., perception of pattern movements and color perception).

Zeki (13) proposed two similar systems in regard to visual information processing. Specifically, the P-cell pathway pertains to color vision and the perception of form that is related to color, whereas the M-cell pathway is related to perception of the form and position of moving objects (movement perception). However, this theory suggests that these pathways are not independent: instead they advance to a higher level while exchanging information and jointly compiling the visual information thus obtained.

According to the studies by Wilkins and Binnie et al. (14–16), oriented lines or oscillating patterns are considered to be more epileptogenic than are checkerboards or static patterns. A spatial frequency of two to four cycles per degree and a reversal frequency of 10–20 Hz have also been shown to be most epileptogenic. Thus the results of the present study are not inconsistent with those of their experiments.

Binnie and Wilkins (16) also stated that the M-cell pathway plays an important role in the two visual information-processing systems described earlier in relation to the pathophysiology of pattern-sensitive epilepsy. They cited the following factors to illustrate the importance of this pathway: (a) the patterns of stripes that differ in brightness are far more epileptogenic than are those with stripes that differ only in color, strongly suggesting the participation by the M-cell pathway without color information; (b) movement perception and binocular vision pertain to information that is processed by the M-cell pathway; (c) flickering pattern stimuli with low spatial frequencies and frequencies >20 Hz are likely to provoke EEG abnormalities, and inferior spatial resolution and detecting speed are characteristic of the M-cell pathway; and (d) EEG abnormality provoked by pattern stimulation, when focal, is usually dominant at the parietal region, which is consistent with the M-cell pathway projecting to the parietal lobe.

Conversely, Harding and Fylan (17) emphasized linear luminance contrast dependency in PPR, in addition to color sensitivity, because they believed that PPR is generated by the P-cell pathway. Porciatti et al. (18) studied patients with photosensitive epilepsy by recording visually evoked potentials in response to temporally modulated patterns of different contrast. Their results also indicated that pattern stimuli of relatively low temporal frequency and high luminance contrast may operate in the cortical hyperexcitability of photosensitive epilepsy (18).

According to the results of the present study, the circumstances for PPR induction by the CRT-pattern test can be described as follows: (a) percentage PPR induction differed according to pattern, with the vertical stripe pattern provoking this response most frequently; (b) percentage PPR provocation also differs depending on spatial frequency (highest at 2.0 to 4.0 cpd); (c) percentage PPR differs depending on pattern-reversal frequencies (highest at 20 Hz); (d) the clarity of the edges of a pattern has no bearing on percentage PPR induction; (e) changes in the brightness of pattern elements do not affect percentage PPR induction; and (f) with the exception of the two subjects who showed dominance of the frontal region, the stimulation caused by pattern movement is not effective in eliciting PPR.

When these findings are superimposed on the characteristics of the two visual information-processing systems described earlier, the P-cell pathway, especially the one traversing the interblob, rather than the M-cell pathway, appears to correspond more closely to the process of PPR provocation. In particular, the lack of significance of brightness perception and the importance of high spatial resolution in provoking PPR differ from the findings of Binnie et al (16). In the present study, spatial frequencies produced the most significant difference in provoking PPR. In other words, PPR was induced more readily with stimulation by finer patterns, and pattern types altered percentage PPR induction. These responses illustrate the characteristics of the P-cell (interblob) pathway that are outstanding in spatial resolution and are essential for “form” perception. Lack of involvement of changes in the brightness and the relative insignificance of pattern movement noted in the test results further illustrate the characteristics of the P-cell (interblob) pathway. However, the observation that the definition of the edges of a pattern is not important in PPR provocation is not consistent with the known characteristics of this pathway. This discrepancy can be explained as follows: when the spatial frequency exceeds 2.0 cpd, it becomes difficult to perceive a difference in the definition of an edge because the pattern is too fine. Another finding, the correlation between pattern-reversal frequency and percentage PPR induction, also is contrary to the characteristics of the P-cell pathway, which is not sensitive to speed. However, pattern-reversal velocity is not believed to be a stimulus related to the speed of pattern movement; rather, like a dot-flickering stimulus, it is related to the synchronicity of the stimulus (i.e., the P-cell pathway is stimulated repeatedly and at regular intervals) and the activation of neurons is synchronized at the cerebral level and induces PPR. In fact, percentage PPR induction is significantly higher at 20 Hz than at lower frequencies, although there was no significant difference between 30 Hz and the lower frequencies. This finding is in agreement with the results of an earlier study indicating that PPR is readily provoked with flickering-flash stimulation at 15 to 20 Hz (19). In other studies, when the number of PPR-positive patients was compared in terms of pattern-reversal frequencies, no significant difference was found. Therefore, as compared with spatial frequencies and pattern types (forms), pattern-reversal frequencies do not constitute an important element in PPR induction.

The present cases showing PPR on the CRT-pattern test were divided into two groups, one with occipital dominance, comprising the majority, and the other with frontal dominance. The two groups reacted differently to pattern stimulation. The latter group included cases in which stimulation with a greater change in the brightness evidently resulted in a higher frequency of PPR or localized spike-and-wave complexes, suggesting the importance of sensitivity to changes in the brightness. When the pattern types were compared, the latter group also included cases in which stimulation caused by a black-and-white pattern or a yellow–blue checkered pattern with little change in the brightness did not provoke PPR; only stimulation by a yellow–black checkered pattern with a greater change in the brightness provoked PPR. This finding suggests that sensitivity to changes in the brightness or color elements (not studied here) has some effect on PPR induction in the latter group. The stimulation caused by pattern movements provoked PPR or localized spike-and-wave complexes in only those cases belonging to the group with frontal dominance, which casts some doubt on the correlation between PPR and pattern movements in this group. Binnie et al. (15) emphasized that the drifting pattern is less epileptogenic than the oscillating and phase-reversing patterns (15). The spatial resolution and brightness-perception tests in the present study used a phase-reversal stimulation method, whereas the pattern movement test used strictly the drifting pattern. The poor activation rate in our pattern-movement test does not contradict that reported by Binnie et al. However, the pattern-movement test, despite producing a less epileptogenic result, might be related to the frontal dominant EEG activation shown in our frontal dominant group.

In examining the significance of spatial frequencies and pattern types in provoking PPR in each individual, most of the cases belonging to the group with occipital dominance showed a significant difference. The correlation obtained between PPR and spatial resolution in this group is probably of importance.

Because the number of patients is small, hasty conclusions are unwarranted. However, the results of this study allow us to hypothesize that patients with ESGS caused by photosensitivity can be divided into two groups: one with occipital dominance for PPR provocation in whom the P-cell (interblob) pathway, which is outstanding in spatial resolution among visual perceptions, is involved; and the other group with frontal dominance for PPR provocation, in whom the M-cell pathway, which is outstanding in brightness perception or perceiving pattern movements among visual perceptions, or the P-cell (blob) that is outstanding in brightness perception or perceiving colors, is involved. Mishkin and Ungerleider (20) stated that the M-cell pathway projects to the parietal cortex. Binnie et al. (16) also emphasized that PPR provoked by pattern stimulation is usually dominant in the parietal region, which is consistent with their observations. However, Goldman-Rakic (21) also suggested that there is a further projection from the parietal to the frontal cortex. Thus our speculation that the M-cell pathway is involved in the group with frontal dominance may not contradict the Mishkin concept. As the number of patients is still too limited to confirm this theory, and our interpretation of the results is inconclusive, especially for the frontal dominant group, it will be necessary to amass data from a larger patient population.

Prevention of ESGS

To prevent ESGS, it is necessary to pay sufficient attention to the physical properties characteristic of the television screen as well as the nature of the visual stimulation associated with the type of game, if the condition is caused by photo-pattern sensitivity. It is difficult to determine who among these 17 patients might have had seizures due to exposure to the television screen itself and how many would have the potential for seizures only in the setting of very specific additional material. If one experienced recurrent seizures induced by a specific game, the cause would be not the television screen itself, but the nature of the visual stimulation associated with the game. In the present study, all nine patients with a positive CRT-pattern test experienced only one episode of ESGS. However, in cases 4, 6, and 7, their ESGS were induced by games on portable LCDs. Generally, LCD shows the effect of afterimage, such that it seems to be less flickering. Furthermore, the LCD itself does not radiate, but rather reflects, the surrounding room light. Thus the cause of ESGS in these three patients might be not the inherent flickering of the television screen itself, but rather the nature of the visual stimulation associated with the game.

In Japan, television sets are manufactured under the NTSC (National Television System Committee) system, with a flickering component of 60 Hz and 30 frames/s. Fylan and Harding (22) described the use of a high frame-rate television as possibly being beneficial in reducing the risk of ESGS caused by photosensitivity. However, it will be more important for patients, who are sensitive to the specific pattern itself within the video game, to avoid the following: (a) geometric patterns (especially vertical stripes) that occupy most of the display; (b) fine patterns with a spatial frequency exceeding 2.0 cpd; (c) rapid (around 20 Hz) pattern-reversal stimulation; (d) patterns with large differences in the brightness; and (e) rapid pattern movements. The establishment of universal guidelines with these recommendations in mind, when creating software for video games, is anticipated to be effective in preventing ESGS caused by photo-pattern sensitivity.

Acknowledgment: Part of this study was introduced at the Third Meeting of the Joint Domestic Study on ESGS (held at Osaka). This study was funded by the aforementioned study group.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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