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A case of Panayiotopoulos syndrome showing an atypical course
Seizure (2006) 15, 643—648
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CASE REPORT
A case of Panayiotopoulos syndrome showing an atypical course Makiko Saitoh a,*, Masaya Kubota b, Ikumi Kimura c, Masashi Mizuguchi a, Takashi Igarashi a a
Department of Pediatrics, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, Japan b Department of Pediatrics, Tokyo Metropolitan Hachiouji Children’s Hospital, Japan c Department of Pediatric Neurology, National Center for Child Health and Development, Japan Received 20 April 2006; received in revised form 27 July 2006; accepted 28 August 2006
KEYWORDS Panayiotopoulos syndrome; Magnetoencephalography; Idiopathic partial epilepsy
Summary We describe herein a patient with Panayiotopoulos syndrome (PS) showing an atypical course. The patient initially had seizures typical of this syndrome from 3 to 5 years of age. EEG showed right occipital high-amplitude sharp and slowwave complexes followed by brief generalized discharges of slow waves. Sequential EEGs obtained from 5 to 11 years of age showed both multifocal discharges and generalized spike and wave complexes. With these changes in EEG findings, the patient experienced various types of seizures. The seizures were frequent and showed oculocephalic deviation followed by absence, atonic seizures, generalized tonic clonic convulsions and clonic seizures of the eyelids, which were observed between 7 and 10 years of age. Antiepileptic drugs were only partially effective for these seizures. Ictal EEG recorded at 8 years of age revealed high-voltage slow waves from the bilateral frontal and occipital regions prior to diffuse high-amplitude spike— wave bursts. At 9 years of age, magnetoencephalography (MEG) revealed the calculated dipoles of the preceding bifrontal spike—wave discharges to be in the frontal areas, while those of the following generalized spike—wave bursts were in the bilateral mid-temporal areas. In PS, reportedly, dipoles of multifocal epileptic discharges are usually located in the occipital and Rolandic areas. The unique clinical evolution in our case may be associated with the unusual frontal localization of dipoles detected by MEG. # 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Introduction
* Corresponding author. Tel.: +81 3 3815 5411x33454; fax: +81 3 3816 4108. E-mail address: [email protected] (M. Saitoh).
Panayiotopoulos syndrome (PS) was first reported as benign childhood epilepsy with occipital paroxysms.1 EEG examinations of patients with PS demonstrated the interictal spike foci to frequently shift
1059-1311/$ — see front matter # 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2006.08.010
644 and become multiple. Despite the multifocal appearance of paroxysmal discharges, PS patients usually have an excellent prognosis.1—7 Dipole source analyses in PS have demonstrated the various types of spikes observed to have similar and stable dipole locations.8—10 We describe herein a patient with an atypical PS course, who showed variable and frequent seizures 4 years after the onset of typical PS. To understand the electrophysiological mechanism in this patient, we identified the epileptic foci using interictal magnetoencephalography (MEG).
Case report This patient was a Japanese girl born to healthy and nonconsanguineous parents, with normal psychomotor development. She had the first PS seizure at 3.5 years of age. In the daytime, she suddenly complained of feeling sick, followed by repeated vomiting and facial pallor, and then upward deviation of the eyes. After being unresponsive for half an hour, she gradually recovered and felt normal after several hours of sleep. Initial EEG at 4 years and 1 month revealed right occipital-dominant, highamplitude sharp and slow-wave complexes followed by a brief generalized discharge of slow waves during sleep (Fig. 1a). Based on the ictal symptoms and EEG findings, the diagnosis of PS was made. Carbamazepine (7 mg/kg/day) was administered,
M. Saitoh et al. and the serum level was maintained at the lower limit of the therapeutic range (4—5 mg/ml). There was an additional similar attack at the age of 5 years. Focal spikes were seen in the right temporal-occipital area on follow-up EEG at 5 years of age (Fig. 2a). At the age of 6 years, the frequency and duration of the generalized discharges were increased during hyperventilation and sleep. Focal spike foci became bilateral and spread to the parieto-occipital area (Fig. 2b). At the age of 7 years, repeated attacks with brief impairment of consciousness were reported by a schoolteacher. Ictal EEG showed occipitally dominant, diffuse and irregular, 2.5 Hz spike—wave bursts lasting about 10 s. Because of these absence-like seizures, the initial diagnosis of PS was questioned. We suspected that the absence-like seizures might have been paradoxically provoked by carbamazepine. Therefore, carbamazepine was discontinued and replaced by valproate, and then by ethosuximide. However, these antiepileptics also had to be abandoned because of liver dysfunction and drug eruption, respectively. The patient did not receive antiepileptic drugs for 2 months. EEG findings remained unchanged, and there were frequent seizures showing oculocephalic deviation followed by brief impairment of consciousness, but no vomiting. Ictal EEG indicated a diffuse, high-amplitude spike—wave burst (Fig. 1b). Preceding high-voltage slow-wave bursts were seen in both the occipital and the
Figure 1 (a) Interictal EEG at the age of 4 years and 1 month, 6 months after the onset of typical autonomic seizures. Right occipital spike—waves were followed by generalized discharges of sharp and slow waves. (b) Ictal EEG at the age of 8 years. While awoke but with her eyes closed, the patient suddenly opened her eyes and became unresponsive. During the initial 2 s of the seizure, EEG showed a bilateral frontal occipital polyspike—wave burst. A subsequent generalized spike— wave burst continued for 5 s (between the two solid triangles), during which the patient remained unresponsive.
A case of Panayiotopoulos syndrome showing an atypical course frontal region. The voltage of the occipital slow waves was higher than that of the frontal waves. At this stage, our patient’s condition was considered to be PS with an atypical evolution. Carbamazepine was again prescribed, and partially alleviated the oculocephalic deviation. However, the frequency of seizures increased again rising to 30 times per day, and was particularly high when the patient was tired. Interictal EEG showed bilateral frontotemporal spikes and slow waves (Fig. 2c) and right-side dominant frontal spike waves followed by a diffuse spike—wave or sharp wave—wave burst. At the age of 8 years, her seizures transiently showed an atonic component. MRI examinations revealed no abnormal findings. At the age of 9 years, zonisamide was added to the treatment regimen and carbamazepine was gradually decreased, resulting in a reduction of ocular deviation attacks, and the appearance of generalized tonic seizures. Taking into account the possibility of paradoxical effects of antiepileptic drugs, zonisamide and carbamazepine were completely stopped at the age of 9 years and 9 months. The frequency of her ocular deviation attacks gradually decreased. Two months after the withdrawal
645
of antiepileptics, she had clonic seizures of the eyelids without impairment of consciousness every day for a month. At 10 years and 3 months of age, she had a seizure with brief impairment of consciousness, and thereafter was seizure-free. The follow-up EEG at 11 years and 4 months of age showed both isolated left-side dominant parietooccipital and temporal-occipital paroxysms and generalized discharges. Generalized discharges were shorter in duration than with previous seizures, were not associated with ictal phenomena such as unresponsiveness, and attenuated when she opened her eyes.
MEG study MEG was done in a magnetically shielded room with a helmet-shaped 204-channel neuromagnetometer (Neuromag Ltd., Finland) at 9 years and 11 months of age, 2 months after withdrawal of antiepileptics. Simultaneously, EEG recordings were obtained. The equivalent current dipoles (ECD) of spikes were fitted by the least-squares method using a single
Figure 2 Serial interictal EEGs. (a) Sleep recording obtained at 5 years of age reveals a right-side temporal-occipital spike. (b) Spike foci became bilateral and had spread to the central and parietal regions by 7 years of age. (c) Spike foci were located bilaterally in the frontotemporal regions at 8 years of age. The patient had frequent seizures with oculochephalic deviation followed by brief impairment of consciousness.
646 equivalent dipole model in a spherical homogeneous conductor.11 The ECD was accepted, if the correlation coefficient of goodness of fit (GOF) was greater than 0.90. The calculated ECDs of spikes involved in generalized spike—wave discharges were
M. Saitoh et al. superimposed on the patient’s MRI to analyze the three-dimensional relationship between MRI findings and the current source localization of the spikes. As shown in Fig. 3, simultaneous EEG demonstrated a bifrontal spike—wave burst followed by
Figure 3 MEG at the age of 10 years. An EEG was recorded simultaneously. Bilateral frontal paroxysms (frame A) preceded generalized discharges (frame C). The current source of the frontal paroxysms appeared to be localized in the anterior frontal area on the MEG study (B). However, this dipole was not stable (GOF = 0.65—0.70). The current sources of the generalized spike and wave discharges were localized in the bilateral the temporal cortices (D). These dipoles were stable and reproducible, with GOF exceeding 0.90.
A case of Panayiotopoulos syndrome showing an atypical course
647
Figure 4 Whole head MEG at the appearance of a generalized spike and wave burst on simultaneous EEG (shown in Fig. 3, frame C).
generalized discharges. The current source of the bifrontal spike—wave was localized in the anterior frontal area on MEG, but this dipole was not stable (GOF = 0.65—0.70). The current source of the generalized spike—wave was localized bilaterally in the temporal cortices, and both dipoles were stable and reproducible (GOF > 0.90) (Figs. 3 and 4).
Discussion In our case, brief impairments of consciousness were seen 4 years after the onset of typical Panayiotopoulos type seizures. Although initially suspected, a paradoxical effect of CBZ12,13 was eventually ruled out because the absence-like seizures persisted despite withdrawal of the antiepileptic drugs and were then accompanied by oculocephalic deviation. We therefore considered this case to represent an atypical course of PS. Caraballo et al. reported a case who initially had typical PS but later showed behavioral and neuropsychological impairments, probably in association with continuous spikes and waves recorded on EEG during slow sleep.14 Although frequent seizures occurred daily for nearly 2 years, our patient showed neither behavioral problems nor intellectual deterioration. During her course, sleep EEG findings were well organized, and no continuous spike—wave pattern was detectable. After the age of 10 years she had only infrequent seizures. Therefore, we considered this patient to have PS of intermediate severity and with an atypical course, resembling the case described by Ferrie et al.15 In our case, seizure type changes were accompanied by variations in EEG findings, such as shifts in EEG foci and increases in both the duration and the frequency of generalized discharges. Such shifts in EEG foci are well known in childhood
epilepsy. Approximately half of the spike foci initially located in the occipital region reportedly move to the frontal region with age.16 Studies on the epileptogenic foci of PS have employed functional neuroimaging or MEG. A patient with typical PS and diffuse spike—wave complexes on EEG showed decreased cerebral blood flow in the occipital region on interictal SPECT.17 Another report described a 6-year-old boy with ocular deviation followed by impairment of consciousness, in whom MEG at age 12 years revealed the estimated dipoles to be clustered in the left cuneus, whereas EEG foci were localized in the left occipital area.8 Recently, Kanazawa et al. conducted a MEG study of 13 patients with PS and found those with typical PS to show ECDs located mainly in the area alongside the parieto-occipital and/or the calcarine sulcus.9 One patient who was regarded as having a combination of PS and atypical benign epilepsy of childhood had relative broad areas of clustered ECDs in the bilateral Rolandic areas. Yoshinaga et al. reported that, despite the multifocal appearance of the spikes in eight children with PS, their dipole locations were stable in the mesial occipital and Rolandic areas.10 They speculated that the good prognosis of PS is related to the marked stability of dipoles, despite the multifocal appearance of spikes. In such patients with typical PS, neither frontal nor temporal ECDs were identified. It is noteworthy that the dipole was detected in the frontal area in our case. Although the frontal dipole GOF was relatively low at the time of MEG examination, its unusual localization may be related to the atypical course in this case. Furthermore, we must consider the possibility that our patient had an element of frontal lobe epilepsy during the course of PS. This possibility cannot be excluded, because frontal lobe epilepsy, particularly of anterior
648 frontopolar origin, may manifest with loss of contact and adverse movements of the eyes and head, both of which were ictal symptoms in this patient. In conclusion, this patient was initially presented with typical PS seizures, but subsequently experienced a variety of seizures not typical of PS. Her unique clinical evolution may be associated with the unusual frontal localization of dipoles detected by MEG.
References 1. Panayiotopoulos CP. Benign childhood epilepsy with occipital paroxysms: a 15-year prospective study. Ann Neurol 1989;26: 51—6. 2. Ferrie CD, Grunewald RA. Panayiotopoulos syndrome: a common and benign childhood epilepsy. Lancet 2001;357:821—3. 3. Panayiotopoulos CP. Early-onset childhood occipital seizure susceptibility syndrome: a syndrome to recognize.. Epilepsia 1999;40:621—30. 4. Oguni H, Hayashi K, Imai K, Hirano Y, Mutoh A, Osawa M. Study of the early-onset variant of benign childhood epilepsy with occipital paroxysms otherwise described as early-onset benign occipital seizure susceptibility syndrome. Epilepsia 1999;40:1020—30. 5. Caraballo R, Cersosimo R, Medina C, Fejerman N. Panayiotopoulos-type benign childhood occipital epilepsy. A prospective study. Neurology 2000;55:1096—100. 6. Kivity S, Ephraim T, Weitz R, Tamir A. Childhood epilepsy with occipital paroxysms: clinical variants in 134 patients. Epilepsia 2000;41:1522—33. 7. Oguni H, Hayashi K, Funatsuka M, Osawa M. Study on earlyonset benign occipital seizure susceptibility syndrome. Pediatr Neurol 2001;25:312—8.
M. Saitoh et al. 8. Sugita K, Kato Y, Sugita K, Kato M, Tanaka Y. Magnetoencephalographic analysis in a case of early-onset benign childhood occipital seizures. J Child Neurol 2002;17: 851—2. 9. Kanazawa O, Tohyama J, Akasaka N, Kamimura T. A magnetoenchephalographic study of patients with Panayiotopoulos syndrome. Epilepsia 2005;46:1106—13. 10. Yoshinaga H, Koutroumanidis M, Shirasawa A, Kikumoto K, Ohtsuka Y, Oka E. Dipole analysis in Panayiotopoulos syndrome. Brain Dev 2005;27:46—52. 11. Hamalainen M, Hari R, Ilmoniemi R, Knuutila J, Lounasmaa OV. Magnetoencephalography: theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev Mod Phys 1993;65:413—97. 12. Snead OC, Hosey C. Exacerbation of seizures in children by carbamazepine. N Engl J Med 1985;313:916—21. 13. Shields WD, Saslow E. Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children. Neurology 1983;33:1487—9. 14. Caraballo RH, Astorino F, Cersosimo R, Soprano AM, Fejerman N. Atypical evolution in childhood epilepsy with occipital paroxysms (Panayiotopoulos type). Epileptic Disord 2001;3: 157—62. 15. Ferrie C, Koutroumanidis M, Rowlinson S, Sanders S, Panayiotopoulos CP. Atypical evolution of Panayiotopoulos syndrome: a case report. Epileptic Disord 2002;4:35—41. 16. Oguni H, Hayash K, Osawa M, Migration of epileptic foci in children.Stefan H, Andermann F, Chuvel P, Shorvon S, editors. Plasticity in epilepsy: dynamic aspects of brain function advances in neurology, vol. 81. Philadelphia, PA: Lippincott, William & Wilkins; 1999. p. 131—43. 17. Sakagami M, Takahashi Y, Matsuoka H, Hoshida T, Izaki K, Nouka S, et al. A case of early-onset benign occipital seizure susceptibility syndrome: decreased cerebral blood flow in the occipital region detected by interictal single photon emission computed tomography, corresponding to the epileptogenic focus. Brain Dev 2001;23:427—30.
www.elsevier.com/locate/yseiz
CASE REPORT
A case of Panayiotopoulos syndrome showing an atypical course Makiko Saitoh a,*, Masaya Kubota b, Ikumi Kimura c, Masashi Mizuguchi a, Takashi Igarashi a a
Department of Pediatrics, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, Japan b Department of Pediatrics, Tokyo Metropolitan Hachiouji Children’s Hospital, Japan c Department of Pediatric Neurology, National Center for Child Health and Development, Japan Received 20 April 2006; received in revised form 27 July 2006; accepted 28 August 2006
KEYWORDS Panayiotopoulos syndrome; Magnetoencephalography; Idiopathic partial epilepsy
Summary We describe herein a patient with Panayiotopoulos syndrome (PS) showing an atypical course. The patient initially had seizures typical of this syndrome from 3 to 5 years of age. EEG showed right occipital high-amplitude sharp and slowwave complexes followed by brief generalized discharges of slow waves. Sequential EEGs obtained from 5 to 11 years of age showed both multifocal discharges and generalized spike and wave complexes. With these changes in EEG findings, the patient experienced various types of seizures. The seizures were frequent and showed oculocephalic deviation followed by absence, atonic seizures, generalized tonic clonic convulsions and clonic seizures of the eyelids, which were observed between 7 and 10 years of age. Antiepileptic drugs were only partially effective for these seizures. Ictal EEG recorded at 8 years of age revealed high-voltage slow waves from the bilateral frontal and occipital regions prior to diffuse high-amplitude spike— wave bursts. At 9 years of age, magnetoencephalography (MEG) revealed the calculated dipoles of the preceding bifrontal spike—wave discharges to be in the frontal areas, while those of the following generalized spike—wave bursts were in the bilateral mid-temporal areas. In PS, reportedly, dipoles of multifocal epileptic discharges are usually located in the occipital and Rolandic areas. The unique clinical evolution in our case may be associated with the unusual frontal localization of dipoles detected by MEG. # 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Introduction
* Corresponding author. Tel.: +81 3 3815 5411x33454; fax: +81 3 3816 4108. E-mail address: [email protected] (M. Saitoh).
Panayiotopoulos syndrome (PS) was first reported as benign childhood epilepsy with occipital paroxysms.1 EEG examinations of patients with PS demonstrated the interictal spike foci to frequently shift
1059-1311/$ — see front matter # 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2006.08.010
644 and become multiple. Despite the multifocal appearance of paroxysmal discharges, PS patients usually have an excellent prognosis.1—7 Dipole source analyses in PS have demonstrated the various types of spikes observed to have similar and stable dipole locations.8—10 We describe herein a patient with an atypical PS course, who showed variable and frequent seizures 4 years after the onset of typical PS. To understand the electrophysiological mechanism in this patient, we identified the epileptic foci using interictal magnetoencephalography (MEG).
Case report This patient was a Japanese girl born to healthy and nonconsanguineous parents, with normal psychomotor development. She had the first PS seizure at 3.5 years of age. In the daytime, she suddenly complained of feeling sick, followed by repeated vomiting and facial pallor, and then upward deviation of the eyes. After being unresponsive for half an hour, she gradually recovered and felt normal after several hours of sleep. Initial EEG at 4 years and 1 month revealed right occipital-dominant, highamplitude sharp and slow-wave complexes followed by a brief generalized discharge of slow waves during sleep (Fig. 1a). Based on the ictal symptoms and EEG findings, the diagnosis of PS was made. Carbamazepine (7 mg/kg/day) was administered,
M. Saitoh et al. and the serum level was maintained at the lower limit of the therapeutic range (4—5 mg/ml). There was an additional similar attack at the age of 5 years. Focal spikes were seen in the right temporal-occipital area on follow-up EEG at 5 years of age (Fig. 2a). At the age of 6 years, the frequency and duration of the generalized discharges were increased during hyperventilation and sleep. Focal spike foci became bilateral and spread to the parieto-occipital area (Fig. 2b). At the age of 7 years, repeated attacks with brief impairment of consciousness were reported by a schoolteacher. Ictal EEG showed occipitally dominant, diffuse and irregular, 2.5 Hz spike—wave bursts lasting about 10 s. Because of these absence-like seizures, the initial diagnosis of PS was questioned. We suspected that the absence-like seizures might have been paradoxically provoked by carbamazepine. Therefore, carbamazepine was discontinued and replaced by valproate, and then by ethosuximide. However, these antiepileptics also had to be abandoned because of liver dysfunction and drug eruption, respectively. The patient did not receive antiepileptic drugs for 2 months. EEG findings remained unchanged, and there were frequent seizures showing oculocephalic deviation followed by brief impairment of consciousness, but no vomiting. Ictal EEG indicated a diffuse, high-amplitude spike—wave burst (Fig. 1b). Preceding high-voltage slow-wave bursts were seen in both the occipital and the
Figure 1 (a) Interictal EEG at the age of 4 years and 1 month, 6 months after the onset of typical autonomic seizures. Right occipital spike—waves were followed by generalized discharges of sharp and slow waves. (b) Ictal EEG at the age of 8 years. While awoke but with her eyes closed, the patient suddenly opened her eyes and became unresponsive. During the initial 2 s of the seizure, EEG showed a bilateral frontal occipital polyspike—wave burst. A subsequent generalized spike— wave burst continued for 5 s (between the two solid triangles), during which the patient remained unresponsive.
A case of Panayiotopoulos syndrome showing an atypical course frontal region. The voltage of the occipital slow waves was higher than that of the frontal waves. At this stage, our patient’s condition was considered to be PS with an atypical evolution. Carbamazepine was again prescribed, and partially alleviated the oculocephalic deviation. However, the frequency of seizures increased again rising to 30 times per day, and was particularly high when the patient was tired. Interictal EEG showed bilateral frontotemporal spikes and slow waves (Fig. 2c) and right-side dominant frontal spike waves followed by a diffuse spike—wave or sharp wave—wave burst. At the age of 8 years, her seizures transiently showed an atonic component. MRI examinations revealed no abnormal findings. At the age of 9 years, zonisamide was added to the treatment regimen and carbamazepine was gradually decreased, resulting in a reduction of ocular deviation attacks, and the appearance of generalized tonic seizures. Taking into account the possibility of paradoxical effects of antiepileptic drugs, zonisamide and carbamazepine were completely stopped at the age of 9 years and 9 months. The frequency of her ocular deviation attacks gradually decreased. Two months after the withdrawal
645
of antiepileptics, she had clonic seizures of the eyelids without impairment of consciousness every day for a month. At 10 years and 3 months of age, she had a seizure with brief impairment of consciousness, and thereafter was seizure-free. The follow-up EEG at 11 years and 4 months of age showed both isolated left-side dominant parietooccipital and temporal-occipital paroxysms and generalized discharges. Generalized discharges were shorter in duration than with previous seizures, were not associated with ictal phenomena such as unresponsiveness, and attenuated when she opened her eyes.
MEG study MEG was done in a magnetically shielded room with a helmet-shaped 204-channel neuromagnetometer (Neuromag Ltd., Finland) at 9 years and 11 months of age, 2 months after withdrawal of antiepileptics. Simultaneously, EEG recordings were obtained. The equivalent current dipoles (ECD) of spikes were fitted by the least-squares method using a single
Figure 2 Serial interictal EEGs. (a) Sleep recording obtained at 5 years of age reveals a right-side temporal-occipital spike. (b) Spike foci became bilateral and had spread to the central and parietal regions by 7 years of age. (c) Spike foci were located bilaterally in the frontotemporal regions at 8 years of age. The patient had frequent seizures with oculochephalic deviation followed by brief impairment of consciousness.
646 equivalent dipole model in a spherical homogeneous conductor.11 The ECD was accepted, if the correlation coefficient of goodness of fit (GOF) was greater than 0.90. The calculated ECDs of spikes involved in generalized spike—wave discharges were
M. Saitoh et al. superimposed on the patient’s MRI to analyze the three-dimensional relationship between MRI findings and the current source localization of the spikes. As shown in Fig. 3, simultaneous EEG demonstrated a bifrontal spike—wave burst followed by
Figure 3 MEG at the age of 10 years. An EEG was recorded simultaneously. Bilateral frontal paroxysms (frame A) preceded generalized discharges (frame C). The current source of the frontal paroxysms appeared to be localized in the anterior frontal area on the MEG study (B). However, this dipole was not stable (GOF = 0.65—0.70). The current sources of the generalized spike and wave discharges were localized in the bilateral the temporal cortices (D). These dipoles were stable and reproducible, with GOF exceeding 0.90.
A case of Panayiotopoulos syndrome showing an atypical course
647
Figure 4 Whole head MEG at the appearance of a generalized spike and wave burst on simultaneous EEG (shown in Fig. 3, frame C).
generalized discharges. The current source of the bifrontal spike—wave was localized in the anterior frontal area on MEG, but this dipole was not stable (GOF = 0.65—0.70). The current source of the generalized spike—wave was localized bilaterally in the temporal cortices, and both dipoles were stable and reproducible (GOF > 0.90) (Figs. 3 and 4).
Discussion In our case, brief impairments of consciousness were seen 4 years after the onset of typical Panayiotopoulos type seizures. Although initially suspected, a paradoxical effect of CBZ12,13 was eventually ruled out because the absence-like seizures persisted despite withdrawal of the antiepileptic drugs and were then accompanied by oculocephalic deviation. We therefore considered this case to represent an atypical course of PS. Caraballo et al. reported a case who initially had typical PS but later showed behavioral and neuropsychological impairments, probably in association with continuous spikes and waves recorded on EEG during slow sleep.14 Although frequent seizures occurred daily for nearly 2 years, our patient showed neither behavioral problems nor intellectual deterioration. During her course, sleep EEG findings were well organized, and no continuous spike—wave pattern was detectable. After the age of 10 years she had only infrequent seizures. Therefore, we considered this patient to have PS of intermediate severity and with an atypical course, resembling the case described by Ferrie et al.15 In our case, seizure type changes were accompanied by variations in EEG findings, such as shifts in EEG foci and increases in both the duration and the frequency of generalized discharges. Such shifts in EEG foci are well known in childhood
epilepsy. Approximately half of the spike foci initially located in the occipital region reportedly move to the frontal region with age.16 Studies on the epileptogenic foci of PS have employed functional neuroimaging or MEG. A patient with typical PS and diffuse spike—wave complexes on EEG showed decreased cerebral blood flow in the occipital region on interictal SPECT.17 Another report described a 6-year-old boy with ocular deviation followed by impairment of consciousness, in whom MEG at age 12 years revealed the estimated dipoles to be clustered in the left cuneus, whereas EEG foci were localized in the left occipital area.8 Recently, Kanazawa et al. conducted a MEG study of 13 patients with PS and found those with typical PS to show ECDs located mainly in the area alongside the parieto-occipital and/or the calcarine sulcus.9 One patient who was regarded as having a combination of PS and atypical benign epilepsy of childhood had relative broad areas of clustered ECDs in the bilateral Rolandic areas. Yoshinaga et al. reported that, despite the multifocal appearance of the spikes in eight children with PS, their dipole locations were stable in the mesial occipital and Rolandic areas.10 They speculated that the good prognosis of PS is related to the marked stability of dipoles, despite the multifocal appearance of spikes. In such patients with typical PS, neither frontal nor temporal ECDs were identified. It is noteworthy that the dipole was detected in the frontal area in our case. Although the frontal dipole GOF was relatively low at the time of MEG examination, its unusual localization may be related to the atypical course in this case. Furthermore, we must consider the possibility that our patient had an element of frontal lobe epilepsy during the course of PS. This possibility cannot be excluded, because frontal lobe epilepsy, particularly of anterior
648 frontopolar origin, may manifest with loss of contact and adverse movements of the eyes and head, both of which were ictal symptoms in this patient. In conclusion, this patient was initially presented with typical PS seizures, but subsequently experienced a variety of seizures not typical of PS. Her unique clinical evolution may be associated with the unusual frontal localization of dipoles detected by MEG.
References 1. Panayiotopoulos CP. Benign childhood epilepsy with occipital paroxysms: a 15-year prospective study. Ann Neurol 1989;26: 51—6. 2. Ferrie CD, Grunewald RA. Panayiotopoulos syndrome: a common and benign childhood epilepsy. Lancet 2001;357:821—3. 3. Panayiotopoulos CP. Early-onset childhood occipital seizure susceptibility syndrome: a syndrome to recognize.. Epilepsia 1999;40:621—30. 4. Oguni H, Hayashi K, Imai K, Hirano Y, Mutoh A, Osawa M. Study of the early-onset variant of benign childhood epilepsy with occipital paroxysms otherwise described as early-onset benign occipital seizure susceptibility syndrome. Epilepsia 1999;40:1020—30. 5. Caraballo R, Cersosimo R, Medina C, Fejerman N. Panayiotopoulos-type benign childhood occipital epilepsy. A prospective study. Neurology 2000;55:1096—100. 6. Kivity S, Ephraim T, Weitz R, Tamir A. Childhood epilepsy with occipital paroxysms: clinical variants in 134 patients. Epilepsia 2000;41:1522—33. 7. Oguni H, Hayashi K, Funatsuka M, Osawa M. Study on earlyonset benign occipital seizure susceptibility syndrome. Pediatr Neurol 2001;25:312—8.
M. Saitoh et al. 8. Sugita K, Kato Y, Sugita K, Kato M, Tanaka Y. Magnetoencephalographic analysis in a case of early-onset benign childhood occipital seizures. J Child Neurol 2002;17: 851—2. 9. Kanazawa O, Tohyama J, Akasaka N, Kamimura T. A magnetoenchephalographic study of patients with Panayiotopoulos syndrome. Epilepsia 2005;46:1106—13. 10. Yoshinaga H, Koutroumanidis M, Shirasawa A, Kikumoto K, Ohtsuka Y, Oka E. Dipole analysis in Panayiotopoulos syndrome. Brain Dev 2005;27:46—52. 11. Hamalainen M, Hari R, Ilmoniemi R, Knuutila J, Lounasmaa OV. Magnetoencephalography: theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev Mod Phys 1993;65:413—97. 12. Snead OC, Hosey C. Exacerbation of seizures in children by carbamazepine. N Engl J Med 1985;313:916—21. 13. Shields WD, Saslow E. Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children. Neurology 1983;33:1487—9. 14. Caraballo RH, Astorino F, Cersosimo R, Soprano AM, Fejerman N. Atypical evolution in childhood epilepsy with occipital paroxysms (Panayiotopoulos type). Epileptic Disord 2001;3: 157—62. 15. Ferrie C, Koutroumanidis M, Rowlinson S, Sanders S, Panayiotopoulos CP. Atypical evolution of Panayiotopoulos syndrome: a case report. Epileptic Disord 2002;4:35—41. 16. Oguni H, Hayash K, Osawa M, Migration of epileptic foci in children.Stefan H, Andermann F, Chuvel P, Shorvon S, editors. Plasticity in epilepsy: dynamic aspects of brain function advances in neurology, vol. 81. Philadelphia, PA: Lippincott, William & Wilkins; 1999. p. 131—43. 17. Sakagami M, Takahashi Y, Matsuoka H, Hoshida T, Izaki K, Nouka S, et al. A case of early-onset benign occipital seizure susceptibility syndrome: decreased cerebral blood flow in the occipital region detected by interictal single photon emission computed tomography, corresponding to the epileptogenic focus. Brain Dev 2001;23:427—30.