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Reflex epilepsy induced by playing Go-stop or Baduk games
Seizure 21 (2012) 770–774
Contents lists available at SciVerse ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Reflex epilepsy induced by playing Go-stop or Baduk games Moon Kyu Lee a,b, JoonSang Yoo a, Yang-Je Cho a,b, Byung In Lee a,b, Kyoung Heo a,b,* a b
Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 April 2012 Received in revised form 19 August 2012 Accepted 21 August 2012
Purpose: Seizures can be triggered by complex mental activities. The aim of this study was to investigate the clinical characteristics of reflex epilepsy induced by playing Go-stop or Baduk games. Methods: The study comprised 11 patients with this type of reflex epilepsy identified from our patient database. We collected data on clinical features, EEG, and brain MRI as well as seizure outcomes. Results: The patients had a late age of onset (range, 43–65 years, except for one patient with an age of onset of 11 years). An MRI abnormality and interictal EEG abnormalities were found in one patient respectively. The seizures exhibited diverse semiological features suggesting a focal or generalized onset. No myoclonic seizures were observed. Individualized strategies such as avoiding the precipitating game or reducing exposure to the stimulus were most effective in preventing the seizures. Conclusion: The pathophysiological mechanisms underlying Go-stop- or Baduk-induced seizures may be different from other cognition-associated reflex epileptic phenomena. This type of reflex epilepsy may be a heterogeneous syndrome manifesting in a range of diverse semiological features. ß 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords: Reflex epilepsy Late age of onset Heterogeneous semiological features Seizure and epilepsy classification Individualized strategy
1. Introduction
2. Methods
Seizures can be triggered by various stimuli, ranging from primary sensory stimuli to more complex mental activities. Since the detailed description of ‘‘epilepsia arithmetices’’ by Ingvar and Nyman in 1962, many cognitive activities have been reported as triggering stimuli.1 These cognitive tasks include calculation, decision making, thinking, Mah-Jong, and card games.2–7 Precipitating cognitive tasks can be single or multiple.8 Typically, the clinical characteristics of cognitive task-induced reflex epilepsy include a young age of onset, absence seizure, myoclonic jerks, and generalized epileptiform discharges on EEG.9,10 However, incongruent findings have also been reported in the literature.6,11–13 The Go-stop game is a poker-like card game played by two to four persons usually for recreation in Korea. Baduk is a popular board game in East Asia including Korea, Japan, and China. Although the provocation of reflex epilepsy by the Go-stop and Baduk games has been previously reported, the delineation of the clinical characteristics thereof has yet to reach a general consensus.11 In this study, we analyzed 11 cases of reflex epilepsy induced by the Go-stop or Baduk games.
We included patients that experienced most of their seizures while playing Go-stop or Baduk games. Eleven patients were selected from the database of the Epilepsy Clinic of Severance Hospital (K. Heo). Clinical information concerning age at onset, family history of epilepsy, significant antecedents for seizure, pre-existing spontaneous seizure, and seizure semiology was collected. Seizure outcomes were also investigated in each patient. All patients underwent scalp EEG recording with nasopharyngeal electrodes and brain MRI scan. Routine scalp EEG recording using the international 10/20 system included sleep deprivation, photic stimulation, and hyperventilation as provocation. One patient underwent prolonged EEG monitoring while playing Baduk. MR studies were performed on either 1.5-T or 3.0-T MR imaging using the same protocol. The following MR images were obtained: axial T2-weighted and FLAIR images as well as T2weighted and FLAIR images in the oblique coronal plane, perpendicular to the long axis of the hippocampus; coronal 3D T1-weighted gradient echo images reconstructed to 1 or 1.5 mm thickness; and axial T1-weighted images with enhancement. The Institutional Review Board of Severance Hospital approved this study. 3. Results 3.1. Demographic data
* Corresponding author at: 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Tel.: +82 2 2228 1607; fax: +82 2 393 0705. E-mail address: [email protected] (K. Heo).
Demographic data are summarized in Table 1. Eight patients were men, and the ages at seizure onset ranged from 11 to 65 years
1059-1311/$ – see front matter ß 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.seizure.2012.08.007
M.K. Lee et al. / Seizure 21 (2012) 770–774
771
Table 1 Demographic and clinical characteristics. No.
Sex/age
Age of onset (yr)
F/U (yr)
Antecedents
FHx
Interictal EEG
Brain MRI
1 2 3 4 5 6
M/50 F/62 M/54 F/66 M/65 F/63
43 55 50 65 61 62
6.7 NA 5.8 2.8 7.1 7.7
( ( ( ( ( (
( ( ( ( ( (
NL NL NL NL NL NL
7 8 9
M/50 M/70 M/32
46 57 11
5.7 5.5 3.8
( ) ( ) FS
( ) ( ) ( )
NL NL NL NL NL Rare left temporal sharp waves NL NL NL
10 11
M/70 M/57
47 51
3.7 NA
( ) ( )
( ) ( )
NL NL
) ) ) ) ) )
) ) ) ) ) )
NL NL Cerebromalacia in both occipital lobes NL NL
F/U, follow-up period; FHx, family history for epilepsy; NA, not available; NL, normal; FS, febrile seizure.
(mean 49.8 years). All patients reported that they had enjoyed the games since adolescence or as a young adult. Ten of the 11 patients experienced only game-related seizures. Among these ten patients, seizures developed in eight patients while playing the games, and occurred additionally, immediately after playing the games in two patients (Patients 1 and 6). The mean age at onset was 53.7 years in the game-related seizure-only group. One patient (Patient 9) with a history of febrile seizure had experienced spontaneous seizures since the age of 11 years. He noticed a close relationship between game playing and seizure occurrence at the age of 20 years old. The duration of epilepsy ranged from one to 23 years (mean 8.3 years) in each patient. There were no significant antecedents, family history for epilepsy, intellectual handicaps, or neurological deficits in all patients, except for Patient 9 with bilateral inferior quadrantanopsia. EEG and MRI findings are summarized in Table 1. Left temporal sharp waves were found in one patient (Patient 6) (Fig. 1). Patient 8 underwent prolonged EEG monitoring while playing Baduk with his friend, but no ictal or interictal discharges were observed. Brain MRIs were normal in ten patients. Patient 9 had cerebromalatic lesions in both occipital lobes, which were presumably related to a perinatal hypoxic insult. None of the patients showed photoparoxysmal responses on EEG.
3.2. Tasks and seizure semiology The types of seizure-evoking task, seizure latency after task, and seizure semiology are described in Table 2. Seven patients (Patients 1, 2, 3, 4, 6, 7, and 11) involved a single trigger of seizure (Go-stop, five patients; Baduk, two patients). Seizures were triggered while playing both Go-stop and Baduk in Patients 5 and 10. In Patient 8, seizures were triggered while playing both Baduk and ‘‘Janggi’’ (Korean chess). One patient (Patient 9) reported playing Baduk and billiards as triggers. Seven patients (Patients 2, 4, 5, 6, 8, 9, and 10) could describe their seizure latencies after beginning to play the games, which were different in each individual, ranging from 0.5 to 7 h after the start of a game. Seizure latencies in two patients (Patients 5 and 10) were different for each game. Seizure latencies varied for each seizure in the others. There were no myoclonic jerks observed in any patient. Ten patients (Patients 1, 2, 3, 4, 5, 7, 8, 9, 10, and 11) exhibited generalized tonic–clonic seizures (GTCSs). Patient 2 experienced only GTCSs. Patient 11 had motionless staring before GTCS. Three patients (Patients 1, 3, and 5) reported nonspecific symptoms such as dizziness, difficulty with concentration, mental clouding, and an indescribable feeling which occurred before GTCS or in isolation. Six patients had irrational speech (Patient 4), a facial expression of
[(Fig._1)TD$IG]
Fig. 1. Interictal EEG of Patient 6 showing left temporal sharp wave (black arrow).
M.K. Lee et al. / Seizure 21 (2012) 770–774
772 Table 2 Seizure manifestation and prognosis. No
Task
Seizure latency after task
Description
Spontaneous seizure
AED
Prognosis
1
Go-stop
VA
( )
None
SF
2 3
Go-stop Baduk
0.5–2 h VA
( ) ( )
VPA None
NA SF
4
Go-stop
6–7 h
( )
VPA
SF
5
Go-stop (later, Baduk)
10 h for Go-stop 3 h for Baduk
( )
VPA
SF
6
Go-stop
3h
( )
LTG
SF
7
Baduk
VA
( )
VPA
SF
8
Baduk (later, Janggi)
1.5 h
( )
LTG
R
9
Baduk and Billiards
0.5–2 h
(+)
CBZ and VPA
R
10
Go-stop and Baduk
6 h for Go-stop, 2 h for Baduk
( )
LTG
SF
11
Go-stop
VA
Prolonged dizziness, difficulty with concentrating, calculating, and paring cards during the game. Two episodes of GTCS preceded by dizziness after finishing the game Seven episodes of GTCS Brief mental clouding (seven episodes evolving into GTCS) One episode of motionless staring with irrational speech, one episode of GTCS Seven episodes of GTCS during Go-stop, indescribable feeling only during Baduk Seven episodes of motionless staring and facial smiling (six episodes occurred during the game, one episode occurred 30 min after finishing the game) Indescribable feeling with or without smelling a strange odor (eight episodes evolving into GTCS) Mental clouding, motionless staring, lip smacking, and automatisms of a right upper extremity during Baduk (seven episodes evolving into GTCS), mental clouding during Janggi Spontaneous and game-related attacks of indescribable feeling with or without conscious version to the right or left side (16 episodes evolving into GTCS during the game) Eight episodes of pain across the entire head followed by conscious version to the left side with clonic movement of the left face (three episodes evolving into GTCS) Four episodes of motionless staring followed by GTCS
( )
None
NA
VA, variable; GTCS, generalized tonic–clonic seizure; AED, antiepileptic drug; LTG, lamotrigine; VPA, valproate; CBZ, carbamazepine; NA, not available; SF, seizure free; R, marked seizure reduction.
laughter (Patient 6), a strange smell (Patient 7), prominent automatisms (Patient 8), and conscious head version or unilateral clonic movements (Patients 9 and 10). Seizure semiologies are described in detail in Table 2. 3.3. Prognosis Nine of the 11 patients were followed-up for a mean of 5.4 years (range, 2.8–7.7 year). Treatment outcomes were unavailable in two patients (Patients 2 and 11) due to a loss of followup. At the initial visit, all patients were recommended to avoid the ‘‘triggering’’ game. Two patients (Patients 1 and 3) accepted the recommendation and received no antiepileptic drug (AED). They achieved seizure freedom. Eight patients were treated with AEDs and five of them achieved seizure freedom (Patients 4, 5, 6, 7, and 10). Patient 4 changed from playing off-line Go-stop game to playing a less-exciting internet based Go-stop game after experiencing seizure relapse. Patient 5 played Baduk instead of Go-stop. Later, he quit playing Baduk due to relapse of a stereotypic indescribable feeling. Patients 6 and 10 reduced the number of times they played in addition the duration of play.
Patient 7 completely discontinued playing games after experiencing seizure relapse. Two patients (Patients 8 and 9) could not achieve seizure freedom. Patient 8 continued game playing. Whenever he felt mental clouding, he withdrew from the game. Patient 9 completely quit games. He is now experiencing rare episodes of auras. Treatment responses are summarized in Table 2. 4. Discussion Reflex epilepsy is defined as recurrent seizures exclusively precipitated by specific stimuli. In 1962, Ingvar and Nyman reported a case of reflex seizure with evidence of activation of generalized epileptiform discharges on EEG by performing calculations and introduced the term ‘‘epilepsia arithmetices’’.1 Since various cognitive tasks are known to trigger reflex seizure, game-induced seizures are naturally incorporated among reflex seizures. The Go-stop game is a Korean card game similar to poker. Baduk is a popular board game in Asia, called ‘‘Weiqi’’ in China and ‘‘Go game’’ in Japan. Janggi is a board game similar to chess.
M.K. Lee et al. / Seizure 21 (2012) 770–774
These games demand complex mental activities including calculation, judgment, prediction, and strategy that are sufficient enough to elicit reflex seizure.11 In 1989, three cases of cognitive task-induced epilepsy, characterized by a young age of onset, generalized epileptiform discharges in EEG, and myoclonic jerks with or without GTCS, were reported.10 These findings were strongly supported by Andermann and colleagues who paid attention to the overlapping clinical features of cognitive task-induced reflex epilepsy with idiopathic generalized epilepsy (IGE).9 They summarized the clinical characteristics as male predominance, adolescent onset, GTCS, co-existing spontaneous generalized seizure, and generalized epileptiform discharges on EEG. In a large group of 480 patients with epilepsy, induction of epileptiform discharges with or without seizures by cognitive activities was found almost exclusively in IGE (36 of 38 patients), particularly juvenile myoclonic epilepsy (JME) (22 of 36; 47% of patients with JME).12 A similar provocative effect was found in 38% of patients with JME in another study.13 However, incongruent findings have also been reported. Wiebers et al. reported an adult-onset reflex seizure induced by calculation with activation of focal (right frontal) epileptiform discharges.14 Anderson and Wallis described a patient with focal EEG abnormalities who showed the activation of generalized spike and slow activity while performing mental arithmetic.2 Also, epileptiform discharges were induced in two patients with temporal lobe epilepsy while performing cognitive activities among 283 patients with focal epilepsy.12 Chuang et al. compared the difference between a Mah-Jong induced seizure only group and a Mah-Jong induced seizure with co-existing spontaneous seizure group.15 The age at onset was significantly older and focal features were more frequent in the Mah-Jong induced seizure only group. Later, they suggested that Mah-Jong induced epilepsy is not in the clinical spectrum of idiopathic generalized epilepsy, considering distinctive clinicoelectrophysiological features, such as late age at onset, different seizure patterns, lack of spontaneous seizures, and the absence of generalized epileptiform discharges.16 In this study, clinically prominent findings included an old age at onset (mean 49.8 years), the absence of spontaneous seizure, variable semiological features, and the frequent association of GTCS. Eight of 11 patients were men, but the male predominance remains uncertain because of the small sample size and the prevalence for males to play these games compared to females. Particularly, Baduk is enjoyed predominantly by men in Korea. The semiological features were heterogeneous in these patients. Five patients experienced isolated attacks of GTCSs or non-specific symptoms of motionless staring, dizziness, mental clouding, and an indescribable feeling before GTCSs. Various prodromal symptoms for the Gostop and Baduk-induced seizures were mentioned in the literature, in which the symptoms were regarded as absence seizures or a part of complex partial seizures.11 Brief focal features, automatisms, asymmetric ictal manifestations, head version, or circling seizure could be manifested in IGE.17–21 Focal EEG features in IGE are often found in the temporal or frontal region, which could be pronounced with aging.22,23 In a recent study, a limited number of late onset IGE patients manifested myoclonic (7.1%) and absence (14.3%) seizures.24 In this study, six patients had focal findings in EEG, MRI, or semiology such as irrational speech, facial expression of laughter, smelling a strange odor, prominent automatisms, conscious head version, and unilateral clonic movements. A family history of epilepsy, which may be a clue for IGE, was not reported among the patients of this study.25 Idiopathic generalized epilepsies usually begin at an early age. Considering the limitations with evaluation methods and the ambiguities of semiological
773
features, classifying seizures as either a generalized or a focal seizure is still difficult in most patients. Nevertheless, the possibility of a focal seizure in these patients should be considered irrespective of the paucity of focal EEG or MRI abnormalities. Little is known about the underlying etiologies of adult onset cognitive task-induced seizure. Most of our patients did not have any etiology or antecedent, as also found in previous studies that evaluated the same type of reflex epilepsy and Mah-Jong induced epilepsy.11,15 Most patients enjoyed games for two to four decades without seizure. Therefore, aging may be an important factor in generation of this type of reflex epilepsy. The brain undergoes nonuniform degeneration with aging.26 Neural plasticity can be modulated by individual specific behaviors for a long time, which may affect the degenerative processes of the brain differently.27–29 The mechanism for the generation of reflex seizure is not yet fully understood. In JME, great effort has been made to shed new light on understanding activation of the reflex circuit. Recently, Vollmar et al., using functional MRI with an executive frontal lobe paradigm in patients with JME, reported increased functional connectivity between the motor system and frontoparietal cognitive networks, and suggested that coactivation of the motor cortex and supplementary motor area as well as increased functional coupling between the motor system and cognitive networks, along with increased cognitive load, provide an explanation for how cognitive effort can cause myoclonic jerks in JME.30 The combination of a cognitive task with a manual motor response was a stronger precipitant of EEG discharges than a purely cognitive task in patients with JME, which may emphasize an involvement of the motor network.12,13 This finding may be in line with continuous manual activities necessary for Go-stop and Baduk games. However, the complexity of cognitive functions and the heterogeneity of environments while playing games made it difficult to depict uniform characteristics in our patients. Many cognitive processes are required to play Go-stop and Baduk games, and one or more of these processes could play a critical role in inducing seizures. Different forms of cognitive processing while performing similar cognitive tasks in each individual may result in the activation of different brain regions. Non-uniform changes with aging and different cognitive processes while performing similar cognitive tasks in each individual may lead to diverse clinical phenotypes. Also, emotional responses and fatigue may be important factors. Patient 8, who failed to show habitual gamerelated seizure during prolonged EEG recording, reported a lesser degree of becoming emotionally upset in the hospitalized setting than in his usual environments of game playing. The internet-based Go-stop game which may produce a lesser degree of mental stress did not provoke seizures in Patient 4, although she did receive AED treatment. Most of our patients required a prolonged time after beginning the games until seizure occurrence, which may suggest that fatigue is necessary to generate such seizures. Treatment responses were favorable among the patients of this study. Individualized strategies such as avoiding the precipitating game or reducing exposure to the stimulus were the most effective. AED treatment alone did not guarantee a favorable outcome, which is supported in the literature.11,31 In conclusion, the semiological features of Go-stop- and Baduk-induced seizures may be different from other cognitionassociated reflex epileptic phenomena. It is presumed that this type of reflex epilepsy may be a heterogeneous syndrome, expressed as diverse semiological features, according to the functionally epileptogenic regions disproportionally affected by aging. Further clarification of the pathogenesis by ictal EEG monitoring and functional neuroimaging is required.
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References 1. Ingvar DH, Nyman GE. Epilepsia arithmetices. Neurology 1962;12:282–7. 2. Anderson NE, Wallis WE. Activation of epileptiform activity by mental arithmetic. Archives of Neurology 1986;43:624–6. 3. Cirignotta F, Cicogna P, Lugaresi E. Epileptic seizures during card games and draughts. Epilepsia 1980;21:137–40. 4. Tatsuzawa Y, Yoshino A, Nomura S. A case of seizures induced by abstract reasoning. Epilepsy & Behavior 2010;17:552–4. 5. Wilkins AJ, Zifkin B, Andermann F, McGovern E. Seizures induced by thinking. Annals of Neurology 1982;11:608–12. 6. Kwan SY, Su MS. Mah-jong epilepsy: a new reflex epilepsy. Zhonghua Yi Xue Za Zhi (Taipei) 2000;63:316–21. 7. Senanayake N. Epileptic seizures evoked by card games, draughts, and similar games. Epilepsia 1987;28:356–61. 8. Ritaccio AL, Singh A, Devinsky O. Cognition-induced epilepsy. Epilepsy & Behavior 2002;3:496–501. 9. Goossens LA, Andermann F, Andermann E, Remillard GM. Reflex seizures induced by calculation, card or board games, and spatial tasks: a review of 25 patients and delineation of the epileptic syndrome. Neurology 1990;40: 1171–6. 10. Senanayake N. Epilepsia arithmetices revisited. Epilepsy Research 1989;3: 167–73. 11. Lee SA, Choi EJ, Kang JK. Reflex epilepsy induced by playing oriental card or board games. Journal of Clinical Neurology 2006;2:262–7. 12. Matsuoka H, Takahashi T, Sasaki M, Matsumoto K, Yoshida S, Numachi Y, et al. Neuropsychological EEG activation in patients with epilepsy. Brain 2000;123:318–30. 13. Guaranha MS, da Silva Sousa P, de Araujo-Filho GM, Lin K, Guilhoto LM, Caboclo LO, et al. Provocative and inhibitory effects of a video-EEG neuropsychologic protocol in juvenile myoclonic epilepsy. Epilepsia 2009;50:2446–55. 14. Wiebers DO, Westmoreland BF, Klass DW. EEG activation and mathematical calculation. Neurology 1979;29:1499–503. 15. Chuang YC, Chang WN, Lin TK, Lu CH, Chen SD, Huang CR. Game-related seizures presenting with two types of clinical features. Seizure 2006;15:98–105. 16. Chang RS, Cheung RT, Ho SL, Mak W. Mah-jong-induced seizures: case reports and review of twenty-three patients. Hong Kong Medical Journal 2007;13:314–8.
17. Leutmezer F, Lurger S, Baumgartner C. Focal features in patients with idiopathic generalized epilepsy. Epilepsy Research 2002;50:293–300. 18. Sadleir LG, Scheffer IE, Smith S, Connolly MB, Farrell K. Automatisms in absence seizures in children with idiopathic generalized epilepsy. Archives of Neurology 2009;66:729–34. 19. Pedersen SB, Petersen KA. Juvenile myoclonic epilepsy: clinical and EEG features. Acta Neurologica Scandinavica 1998;97:160–3. 20. Aguglia U, Gambardella A, Le Piane E, Messina D, Russo C, Oliveri RL, et al. Idiopathic generalized epilepsies with versive or circling seizures. Acta Neurologica Scandinavica 1999;99:219–24. 21. Saka E, Saygi S, Ciger A, Selekler K. Circling seizures. Seizure 1996;5:299–302. 22. Lombroso CT, Consistent EEG. focalities detected in subjects with primary generalized epilepsies monitored for two decades. Epilepsia 1997;38:797–812. 23. Betting LE, Mory SB, Lopes-Cendes I, Li LM, Guerreiro MM, Guerreiro CA, et al. EEG features in idiopathic generalized epilepsy: clues to diagnosis. Epilepsia 2006;47:523–8. 24. Reichsoellner J, Larch J, Unterberger I, Dobesberger J, Kuchukhidze G, Luef G, et al. Idiopathic generalised epilepsy of late onset: a separate nosological entity? Journal of Neurology Neurosurgery and Psychiatry 2010;81:1218–22. 25. Marini C, King MA, Archer JS, Newton MR, Berkovic SF. Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics. Journal of Neurology Neurosurgery and Psychiatry 2003;74:192–6. 26. Terry RD, DeTeresa R, Hansen LA. Neocortical cell counts in normal human adult aging. Annals of Neurology 1987;21:530–9. 27. Gaser C, Schlaug G. Gray matter differences between musicians and nonmusicians. Annals of the New York Academy of Sciences 2003;999:514–7. 28. Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A. Neuroplasticity: changes in grey matter induced by training. Nature 2004;427:311–2. 29. Bonilha L, Eckert MA, Fridriksson J, Hirth VA, Moser D, Morgan PS, et al. Agerelated relative volume preservation of the dominant hand cortical region. Brain Research 2009;1305:14–9. 30. Vollmar C, O’Muircheartaigh J, Barker GJ, Symms MR, Thompson P, Kumari V, et al. Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study. Brain 2011;134: 1710–9. 31. Zeki G, Ilker IH, Hidir UU, Zeki O. Hot water epilepsy: seizure type, water temperature, EEG findings and treatment. Neurologist 2010;16:109–12.
Contents lists available at SciVerse ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Reflex epilepsy induced by playing Go-stop or Baduk games Moon Kyu Lee a,b, JoonSang Yoo a, Yang-Je Cho a,b, Byung In Lee a,b, Kyoung Heo a,b,* a b
Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 April 2012 Received in revised form 19 August 2012 Accepted 21 August 2012
Purpose: Seizures can be triggered by complex mental activities. The aim of this study was to investigate the clinical characteristics of reflex epilepsy induced by playing Go-stop or Baduk games. Methods: The study comprised 11 patients with this type of reflex epilepsy identified from our patient database. We collected data on clinical features, EEG, and brain MRI as well as seizure outcomes. Results: The patients had a late age of onset (range, 43–65 years, except for one patient with an age of onset of 11 years). An MRI abnormality and interictal EEG abnormalities were found in one patient respectively. The seizures exhibited diverse semiological features suggesting a focal or generalized onset. No myoclonic seizures were observed. Individualized strategies such as avoiding the precipitating game or reducing exposure to the stimulus were most effective in preventing the seizures. Conclusion: The pathophysiological mechanisms underlying Go-stop- or Baduk-induced seizures may be different from other cognition-associated reflex epileptic phenomena. This type of reflex epilepsy may be a heterogeneous syndrome manifesting in a range of diverse semiological features. ß 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords: Reflex epilepsy Late age of onset Heterogeneous semiological features Seizure and epilepsy classification Individualized strategy
1. Introduction
2. Methods
Seizures can be triggered by various stimuli, ranging from primary sensory stimuli to more complex mental activities. Since the detailed description of ‘‘epilepsia arithmetices’’ by Ingvar and Nyman in 1962, many cognitive activities have been reported as triggering stimuli.1 These cognitive tasks include calculation, decision making, thinking, Mah-Jong, and card games.2–7 Precipitating cognitive tasks can be single or multiple.8 Typically, the clinical characteristics of cognitive task-induced reflex epilepsy include a young age of onset, absence seizure, myoclonic jerks, and generalized epileptiform discharges on EEG.9,10 However, incongruent findings have also been reported in the literature.6,11–13 The Go-stop game is a poker-like card game played by two to four persons usually for recreation in Korea. Baduk is a popular board game in East Asia including Korea, Japan, and China. Although the provocation of reflex epilepsy by the Go-stop and Baduk games has been previously reported, the delineation of the clinical characteristics thereof has yet to reach a general consensus.11 In this study, we analyzed 11 cases of reflex epilepsy induced by the Go-stop or Baduk games.
We included patients that experienced most of their seizures while playing Go-stop or Baduk games. Eleven patients were selected from the database of the Epilepsy Clinic of Severance Hospital (K. Heo). Clinical information concerning age at onset, family history of epilepsy, significant antecedents for seizure, pre-existing spontaneous seizure, and seizure semiology was collected. Seizure outcomes were also investigated in each patient. All patients underwent scalp EEG recording with nasopharyngeal electrodes and brain MRI scan. Routine scalp EEG recording using the international 10/20 system included sleep deprivation, photic stimulation, and hyperventilation as provocation. One patient underwent prolonged EEG monitoring while playing Baduk. MR studies were performed on either 1.5-T or 3.0-T MR imaging using the same protocol. The following MR images were obtained: axial T2-weighted and FLAIR images as well as T2weighted and FLAIR images in the oblique coronal plane, perpendicular to the long axis of the hippocampus; coronal 3D T1-weighted gradient echo images reconstructed to 1 or 1.5 mm thickness; and axial T1-weighted images with enhancement. The Institutional Review Board of Severance Hospital approved this study. 3. Results 3.1. Demographic data
* Corresponding author at: 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Tel.: +82 2 2228 1607; fax: +82 2 393 0705. E-mail address: [email protected] (K. Heo).
Demographic data are summarized in Table 1. Eight patients were men, and the ages at seizure onset ranged from 11 to 65 years
1059-1311/$ – see front matter ß 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.seizure.2012.08.007
M.K. Lee et al. / Seizure 21 (2012) 770–774
771
Table 1 Demographic and clinical characteristics. No.
Sex/age
Age of onset (yr)
F/U (yr)
Antecedents
FHx
Interictal EEG
Brain MRI
1 2 3 4 5 6
M/50 F/62 M/54 F/66 M/65 F/63
43 55 50 65 61 62
6.7 NA 5.8 2.8 7.1 7.7
( ( ( ( ( (
( ( ( ( ( (
NL NL NL NL NL NL
7 8 9
M/50 M/70 M/32
46 57 11
5.7 5.5 3.8
( ) ( ) FS
( ) ( ) ( )
NL NL NL NL NL Rare left temporal sharp waves NL NL NL
10 11
M/70 M/57
47 51
3.7 NA
( ) ( )
( ) ( )
NL NL
) ) ) ) ) )
) ) ) ) ) )
NL NL Cerebromalacia in both occipital lobes NL NL
F/U, follow-up period; FHx, family history for epilepsy; NA, not available; NL, normal; FS, febrile seizure.
(mean 49.8 years). All patients reported that they had enjoyed the games since adolescence or as a young adult. Ten of the 11 patients experienced only game-related seizures. Among these ten patients, seizures developed in eight patients while playing the games, and occurred additionally, immediately after playing the games in two patients (Patients 1 and 6). The mean age at onset was 53.7 years in the game-related seizure-only group. One patient (Patient 9) with a history of febrile seizure had experienced spontaneous seizures since the age of 11 years. He noticed a close relationship between game playing and seizure occurrence at the age of 20 years old. The duration of epilepsy ranged from one to 23 years (mean 8.3 years) in each patient. There were no significant antecedents, family history for epilepsy, intellectual handicaps, or neurological deficits in all patients, except for Patient 9 with bilateral inferior quadrantanopsia. EEG and MRI findings are summarized in Table 1. Left temporal sharp waves were found in one patient (Patient 6) (Fig. 1). Patient 8 underwent prolonged EEG monitoring while playing Baduk with his friend, but no ictal or interictal discharges were observed. Brain MRIs were normal in ten patients. Patient 9 had cerebromalatic lesions in both occipital lobes, which were presumably related to a perinatal hypoxic insult. None of the patients showed photoparoxysmal responses on EEG.
3.2. Tasks and seizure semiology The types of seizure-evoking task, seizure latency after task, and seizure semiology are described in Table 2. Seven patients (Patients 1, 2, 3, 4, 6, 7, and 11) involved a single trigger of seizure (Go-stop, five patients; Baduk, two patients). Seizures were triggered while playing both Go-stop and Baduk in Patients 5 and 10. In Patient 8, seizures were triggered while playing both Baduk and ‘‘Janggi’’ (Korean chess). One patient (Patient 9) reported playing Baduk and billiards as triggers. Seven patients (Patients 2, 4, 5, 6, 8, 9, and 10) could describe their seizure latencies after beginning to play the games, which were different in each individual, ranging from 0.5 to 7 h after the start of a game. Seizure latencies in two patients (Patients 5 and 10) were different for each game. Seizure latencies varied for each seizure in the others. There were no myoclonic jerks observed in any patient. Ten patients (Patients 1, 2, 3, 4, 5, 7, 8, 9, 10, and 11) exhibited generalized tonic–clonic seizures (GTCSs). Patient 2 experienced only GTCSs. Patient 11 had motionless staring before GTCS. Three patients (Patients 1, 3, and 5) reported nonspecific symptoms such as dizziness, difficulty with concentration, mental clouding, and an indescribable feeling which occurred before GTCS or in isolation. Six patients had irrational speech (Patient 4), a facial expression of
[(Fig._1)TD$IG]
Fig. 1. Interictal EEG of Patient 6 showing left temporal sharp wave (black arrow).
M.K. Lee et al. / Seizure 21 (2012) 770–774
772 Table 2 Seizure manifestation and prognosis. No
Task
Seizure latency after task
Description
Spontaneous seizure
AED
Prognosis
1
Go-stop
VA
( )
None
SF
2 3
Go-stop Baduk
0.5–2 h VA
( ) ( )
VPA None
NA SF
4
Go-stop
6–7 h
( )
VPA
SF
5
Go-stop (later, Baduk)
10 h for Go-stop 3 h for Baduk
( )
VPA
SF
6
Go-stop
3h
( )
LTG
SF
7
Baduk
VA
( )
VPA
SF
8
Baduk (later, Janggi)
1.5 h
( )
LTG
R
9
Baduk and Billiards
0.5–2 h
(+)
CBZ and VPA
R
10
Go-stop and Baduk
6 h for Go-stop, 2 h for Baduk
( )
LTG
SF
11
Go-stop
VA
Prolonged dizziness, difficulty with concentrating, calculating, and paring cards during the game. Two episodes of GTCS preceded by dizziness after finishing the game Seven episodes of GTCS Brief mental clouding (seven episodes evolving into GTCS) One episode of motionless staring with irrational speech, one episode of GTCS Seven episodes of GTCS during Go-stop, indescribable feeling only during Baduk Seven episodes of motionless staring and facial smiling (six episodes occurred during the game, one episode occurred 30 min after finishing the game) Indescribable feeling with or without smelling a strange odor (eight episodes evolving into GTCS) Mental clouding, motionless staring, lip smacking, and automatisms of a right upper extremity during Baduk (seven episodes evolving into GTCS), mental clouding during Janggi Spontaneous and game-related attacks of indescribable feeling with or without conscious version to the right or left side (16 episodes evolving into GTCS during the game) Eight episodes of pain across the entire head followed by conscious version to the left side with clonic movement of the left face (three episodes evolving into GTCS) Four episodes of motionless staring followed by GTCS
( )
None
NA
VA, variable; GTCS, generalized tonic–clonic seizure; AED, antiepileptic drug; LTG, lamotrigine; VPA, valproate; CBZ, carbamazepine; NA, not available; SF, seizure free; R, marked seizure reduction.
laughter (Patient 6), a strange smell (Patient 7), prominent automatisms (Patient 8), and conscious head version or unilateral clonic movements (Patients 9 and 10). Seizure semiologies are described in detail in Table 2. 3.3. Prognosis Nine of the 11 patients were followed-up for a mean of 5.4 years (range, 2.8–7.7 year). Treatment outcomes were unavailable in two patients (Patients 2 and 11) due to a loss of followup. At the initial visit, all patients were recommended to avoid the ‘‘triggering’’ game. Two patients (Patients 1 and 3) accepted the recommendation and received no antiepileptic drug (AED). They achieved seizure freedom. Eight patients were treated with AEDs and five of them achieved seizure freedom (Patients 4, 5, 6, 7, and 10). Patient 4 changed from playing off-line Go-stop game to playing a less-exciting internet based Go-stop game after experiencing seizure relapse. Patient 5 played Baduk instead of Go-stop. Later, he quit playing Baduk due to relapse of a stereotypic indescribable feeling. Patients 6 and 10 reduced the number of times they played in addition the duration of play.
Patient 7 completely discontinued playing games after experiencing seizure relapse. Two patients (Patients 8 and 9) could not achieve seizure freedom. Patient 8 continued game playing. Whenever he felt mental clouding, he withdrew from the game. Patient 9 completely quit games. He is now experiencing rare episodes of auras. Treatment responses are summarized in Table 2. 4. Discussion Reflex epilepsy is defined as recurrent seizures exclusively precipitated by specific stimuli. In 1962, Ingvar and Nyman reported a case of reflex seizure with evidence of activation of generalized epileptiform discharges on EEG by performing calculations and introduced the term ‘‘epilepsia arithmetices’’.1 Since various cognitive tasks are known to trigger reflex seizure, game-induced seizures are naturally incorporated among reflex seizures. The Go-stop game is a Korean card game similar to poker. Baduk is a popular board game in Asia, called ‘‘Weiqi’’ in China and ‘‘Go game’’ in Japan. Janggi is a board game similar to chess.
M.K. Lee et al. / Seizure 21 (2012) 770–774
These games demand complex mental activities including calculation, judgment, prediction, and strategy that are sufficient enough to elicit reflex seizure.11 In 1989, three cases of cognitive task-induced epilepsy, characterized by a young age of onset, generalized epileptiform discharges in EEG, and myoclonic jerks with or without GTCS, were reported.10 These findings were strongly supported by Andermann and colleagues who paid attention to the overlapping clinical features of cognitive task-induced reflex epilepsy with idiopathic generalized epilepsy (IGE).9 They summarized the clinical characteristics as male predominance, adolescent onset, GTCS, co-existing spontaneous generalized seizure, and generalized epileptiform discharges on EEG. In a large group of 480 patients with epilepsy, induction of epileptiform discharges with or without seizures by cognitive activities was found almost exclusively in IGE (36 of 38 patients), particularly juvenile myoclonic epilepsy (JME) (22 of 36; 47% of patients with JME).12 A similar provocative effect was found in 38% of patients with JME in another study.13 However, incongruent findings have also been reported. Wiebers et al. reported an adult-onset reflex seizure induced by calculation with activation of focal (right frontal) epileptiform discharges.14 Anderson and Wallis described a patient with focal EEG abnormalities who showed the activation of generalized spike and slow activity while performing mental arithmetic.2 Also, epileptiform discharges were induced in two patients with temporal lobe epilepsy while performing cognitive activities among 283 patients with focal epilepsy.12 Chuang et al. compared the difference between a Mah-Jong induced seizure only group and a Mah-Jong induced seizure with co-existing spontaneous seizure group.15 The age at onset was significantly older and focal features were more frequent in the Mah-Jong induced seizure only group. Later, they suggested that Mah-Jong induced epilepsy is not in the clinical spectrum of idiopathic generalized epilepsy, considering distinctive clinicoelectrophysiological features, such as late age at onset, different seizure patterns, lack of spontaneous seizures, and the absence of generalized epileptiform discharges.16 In this study, clinically prominent findings included an old age at onset (mean 49.8 years), the absence of spontaneous seizure, variable semiological features, and the frequent association of GTCS. Eight of 11 patients were men, but the male predominance remains uncertain because of the small sample size and the prevalence for males to play these games compared to females. Particularly, Baduk is enjoyed predominantly by men in Korea. The semiological features were heterogeneous in these patients. Five patients experienced isolated attacks of GTCSs or non-specific symptoms of motionless staring, dizziness, mental clouding, and an indescribable feeling before GTCSs. Various prodromal symptoms for the Gostop and Baduk-induced seizures were mentioned in the literature, in which the symptoms were regarded as absence seizures or a part of complex partial seizures.11 Brief focal features, automatisms, asymmetric ictal manifestations, head version, or circling seizure could be manifested in IGE.17–21 Focal EEG features in IGE are often found in the temporal or frontal region, which could be pronounced with aging.22,23 In a recent study, a limited number of late onset IGE patients manifested myoclonic (7.1%) and absence (14.3%) seizures.24 In this study, six patients had focal findings in EEG, MRI, or semiology such as irrational speech, facial expression of laughter, smelling a strange odor, prominent automatisms, conscious head version, and unilateral clonic movements. A family history of epilepsy, which may be a clue for IGE, was not reported among the patients of this study.25 Idiopathic generalized epilepsies usually begin at an early age. Considering the limitations with evaluation methods and the ambiguities of semiological
773
features, classifying seizures as either a generalized or a focal seizure is still difficult in most patients. Nevertheless, the possibility of a focal seizure in these patients should be considered irrespective of the paucity of focal EEG or MRI abnormalities. Little is known about the underlying etiologies of adult onset cognitive task-induced seizure. Most of our patients did not have any etiology or antecedent, as also found in previous studies that evaluated the same type of reflex epilepsy and Mah-Jong induced epilepsy.11,15 Most patients enjoyed games for two to four decades without seizure. Therefore, aging may be an important factor in generation of this type of reflex epilepsy. The brain undergoes nonuniform degeneration with aging.26 Neural plasticity can be modulated by individual specific behaviors for a long time, which may affect the degenerative processes of the brain differently.27–29 The mechanism for the generation of reflex seizure is not yet fully understood. In JME, great effort has been made to shed new light on understanding activation of the reflex circuit. Recently, Vollmar et al., using functional MRI with an executive frontal lobe paradigm in patients with JME, reported increased functional connectivity between the motor system and frontoparietal cognitive networks, and suggested that coactivation of the motor cortex and supplementary motor area as well as increased functional coupling between the motor system and cognitive networks, along with increased cognitive load, provide an explanation for how cognitive effort can cause myoclonic jerks in JME.30 The combination of a cognitive task with a manual motor response was a stronger precipitant of EEG discharges than a purely cognitive task in patients with JME, which may emphasize an involvement of the motor network.12,13 This finding may be in line with continuous manual activities necessary for Go-stop and Baduk games. However, the complexity of cognitive functions and the heterogeneity of environments while playing games made it difficult to depict uniform characteristics in our patients. Many cognitive processes are required to play Go-stop and Baduk games, and one or more of these processes could play a critical role in inducing seizures. Different forms of cognitive processing while performing similar cognitive tasks in each individual may result in the activation of different brain regions. Non-uniform changes with aging and different cognitive processes while performing similar cognitive tasks in each individual may lead to diverse clinical phenotypes. Also, emotional responses and fatigue may be important factors. Patient 8, who failed to show habitual gamerelated seizure during prolonged EEG recording, reported a lesser degree of becoming emotionally upset in the hospitalized setting than in his usual environments of game playing. The internet-based Go-stop game which may produce a lesser degree of mental stress did not provoke seizures in Patient 4, although she did receive AED treatment. Most of our patients required a prolonged time after beginning the games until seizure occurrence, which may suggest that fatigue is necessary to generate such seizures. Treatment responses were favorable among the patients of this study. Individualized strategies such as avoiding the precipitating game or reducing exposure to the stimulus were the most effective. AED treatment alone did not guarantee a favorable outcome, which is supported in the literature.11,31 In conclusion, the semiological features of Go-stop- and Baduk-induced seizures may be different from other cognitionassociated reflex epileptic phenomena. It is presumed that this type of reflex epilepsy may be a heterogeneous syndrome, expressed as diverse semiological features, according to the functionally epileptogenic regions disproportionally affected by aging. Further clarification of the pathogenesis by ictal EEG monitoring and functional neuroimaging is required.
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