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Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia
Brain & Development 22 (2000) 135±138
Case report
www.elsevier.com/locate/braindev
Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia Yoko Ohtsuka*, Masahiro Sato, Satoshi Sanada, Harumi Yoshinaga, Eiji Oka Department of Child Neurology, Okayama University Medical School, 2-5-1, Shikatacho, Okayama, Japan Received 3 September 1999; received in revised form 10 December 1999; accepted 13 December 1999
Abstract We report on a patient with early-onset spasms in series and partial seizures associated with focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy. These electroclinical characteristics suggested a diagnosis of Ohtahara syndrome, but the EEG ®ndings were atypical because of the lack of suppression-burst patterns during wakefulness. In addition, the patient did not have severe psychomotor retardation. With high-dose pyridoxal phosphate therapy, seizures were suppressed and suppression-burst patterns disappeared at 2 months of age. Focal motor seizures recurred later and they often evolved into epilepsia partialis continua. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEGs have several different etiologies, and these patients should be categorized according to their etiology in addition to their syndromic diagnosis. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Focal cortical dysplasia; Suppression-burst pattern; Spasms; Ohtahara syndrome; Early-infantile epileptic encephalopathy with suppression bursts
1. Introduction Some patients with focal cortical dysplasia show earlyonset spasms in series often associated with partial seizures [1,2]. When the EEGs of these patients reveal suppressionburst patterns, they might be diagnosed as having early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome) [3,4]. On the other hand, some cases of early myoclonic encephalopathy, early-onset West syndrome or localized brain malformations, such as hemimegalencephaly, share some ®ndings with cases of Ohtahara syndrome [5]. Thus, the boundaries of Ohtahara syndrome are not necessarily clear even though it is a clearly de®ned electroclinical entity [5]. Herein we report on and discuss a patient with early-onset intractable seizures and focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy.
2. Case report The patient is a 6-year 5-month-old boy. At 2 weeks after birth he began to have spasms in series which looked symmetrical. In addition, focal clonic convulsions involving the left corner of the mouth, the left eyelid and the left arm * Corresponding author. Tel.: 181-86-223-7151; fax: 181-86-2357377.
lasting several seconds to several dozens of seconds began to occur. He was referred to us at 1 month 21 days of age after having been placed on a therapy of 30 mg of phenytoin, 150 mg of valproate and 150 mg of pyridoxal phosphate daily. The EEG on admission showed unilateral suppression-burst patterns on the right side during sleep (Fig. 1). During wakefulness, EEGs showed a basic pattern of asymmetry with more slow waves in the right hemisphere, and multifocal spikes and multifocal spike-waves were observed mainly in the right central region without suppression-burst patterns. Simultaneous video-EEG-EMG polygraphic recordings revealed three types of seizures: a partial seizure followed by spasms in series; a partial seizure followed by spasms in series interspersed with several partial seizures; and spasms in series only. No myoclonus were detected by means of long-term simultaneous video-EEG-EMG polygraphic recordings. At 2 months 2 weeks of age all types of seizures were suppressed by increasing the dosage of pyridoxal phosphate to 360 mg/day. His EEGs also improved dramatically, and suppression-burst patterns disappeared. The patient was free from seizures on the monotherapy of pyridoxal phosphate until one year of age when focal clonic convulsions involving the left upper limb recurred. These focal motor seizures often evolved into epilepsia partialis continua (EPC). Interictal EEGs showed frequent 1.5±2 Hz slow spike-waves in the right frontal-central region in addi-
0387-7604/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S 0387-760 4(00)00090-5
136
Y. Ohtsuka et al. / Brain & Development 22 (2000) 135±138
Fig. 1. Interictal EEG at 1 month of age. During sleep unilateral suppression-burst patterns are observed on the right hemisphere. Calibration: 50 mV, 1 s.
tion to multifocal spikes/spike-waves and infrequent diffuse spike-waves and diffuse slow spike-waves. Ictal EEGs of focal motor seizures revealed 2.5±3 Hz spike-wave complexes in the right frontal-central region. An MRI at 1
year 3 months of age clearly revealed focal cortical dysplasia in the right frontal region (Fig. 2). An interictal SPECT with 99mTc-HMPAO revealed hypoperfusion in the same region. Proton magnetic resonance spectroscopic imaging
Fig. 2. Sagittal and axial MRI scans [3D MP±RAGE:TR(ms)/TE(ms)/TI(ms)/¯ip angle(8) 10/4/300/10] at 2 years 2 month of age shows a focal cortical dysplasia in the right frontal lobe in which the increased thickness of the cortex and widened cerebral sulci are visible (arrow heads).
Y. Ohtsuka et al. / Brain & Development 22 (2000) 135±138
( 1H-MRSI) showed a decrease in the N-acetylaspartate/ creatine (NAA/Cr) resonance intensity ratio in the right frontal lesion compared with the corresponding region in the left frontal lobe (1.95 in the right frontal lobe; 2.89 in the left frontal lobe). At 1 year 11 months of age, he began to have complex partial seizures, and at 2 years 1 month of age, these evolved into status epilepticus. Conversely, the focal motor seizures disappeared. Drip infusion of lidocaine (4 mg/kg per h) suppressed the complex partial status epilepticus. Five months later, focal motor seizures and EPC recurred. In spite of the persistence of seizures and the deterioration of the EEG ®ndings, his mental functions gradually developed. He started walking at 1 year 6 months of age, and saying meaningful words at 2 years 3 months of age. His developmental quotient as assessed by Enjoji Developmental Scales, was 57 at the age of 6 years 5 months. At 6 months of age, mild paresis of the left upper limb was noted. At 4 years 1 month of age, he underwent subpial transection of the right frontal lobe. The frequency of seizures gradually decreased after the surgery. He has had several focal motor seizures per week without EPC for the previous 6 months. His recent EEGs showed continuous epileptic discharges in the right frontal region without generalization of focal epileptic discharges (Fig. 3).
3. Discussion During the ®rst 2 months of this patient's life, his EEGs
Fig. 3. Interictal EEG during drowsy state at 6 years 5 months of age. Continuous spikes are observed on the right frontal region without generalization both during waking and sleeping states. Calibration: 50 mV, 1 s.
137
showed suppression-burst patterns only during sleep. In typical cases of Ohtahara syndrome, suppression-burst patterns appear both during waking and sleeping states [5]. It is speculated that suppression-burst patterns are caused by a subcortical-cortical regulation disorder, which is also associated with severe dysfunction of the cortex [5]. If this dysfunction is very severe, suppression-burst patterns appear both during waking and sleeping states. However, if this dysfunction is not very severe, suppression-burst patterns might be observed only during sleep. Thus, it is likely that the mode of appearance of suppression-burst patterns depends on the condition of the cortex. In this patient, the function of other cortical areas seems to be preserved relatively well because he does not suffer from severe psychomotor retardation and MRI ®ndings are almost normal for other cortical areas. Regarding the relationship between brain malformations such as focal cortical dysplasia and suppression-burst patterns on EEGs, it has been reported that a patient with olivary-dentate dysplasia showed early-onset partial seizures associated with suppression-burst patterns only during sleep on EEGs [6]. It is also well known that unilateral suppression-burst patterns are observed in hemimegalencephaly mostly during the ®rst few months after birth [7]. Moreover, some patients with hemimegalencephaly show early-onset partial seizures associated with suppression-burst patterns only during sleep [8]. These patients cannot be classi®ed as suffering from Ohtahara syndrome in the narrow sense because of the lack of tonic spasms and suppression-burst patterns during wakefulness. However, the diagnosis of Ohtahara syndrome is justi®ed if patients with hemimegalencephaly show early onset spasms in series and suppression-burst patterns on EEG both during waking and sleeping states [5,8]. Regarding the diagnosis of the patient in this report, in addition to his atypical EEG ®ndings, he has relatively favorable mental and motor development, compared with typical cases of Ohtahara syndrome. In conclusion, the diagnosis of Ohtahara syndrome is not justi®ed for this patient. However, the fact that there are some cases of Ohtahara syndrome associated with localized brain malformations, such as hemimegalencephaly and focal cortical dysplasia, and the similarity in electroclinical ®ndings between this case and some of the other cases mentioned herein may indicate that they share some of the same pathophysiological mechanisms. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEG have several different etiologies [3±8], and they should be categorized according to their etiology in addition to their syndromic diagnosis. Characteristic continuous or recurrent epileptic discharges on electrocorticograms [9] and rhythmic epileptiform discharges on scalp EEGs [10] have been reported in patients with focal cortical dysplasia and intractable epilepsy. However, changes in EEG ®ndings with age in these patients have not been clari®ed. EEGs of our patient
138
Y. Ohtsuka et al. / Brain & Development 22 (2000) 135±138
showed the characteristic change from unilateral suppression-burst patterns into continuous epileptic discharges in the region corresponding to the focal cortical dysplasia with increasing age. In order to use EEGs more speci®cally in the diagnosis of brain malformations, more detailed studies on age-dependent changes in EEG abnormalities are needed. References [1] Dulac O, Pinard JM, Plouin P. Infantile spasms associated with cortical dysplasia and tuberous sclerosis. In: Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin BG, Pfanner P, eds. Dysplasias of cerebral cortex and epilepsy, Philadelphia: Lippincott-Raven, 1996. pp. 217±225. [2] Ohtsuka Y. West syndrome and its related epileptic syndromes. Epilepsia 1998;39(Suppl 5):30±37. [3] Pedespan JM, Loiseau H, Vital A, Marchal C, Fontan D, Rougier A. Surgical treatment of an early epileptic encephalopathy with suppression-bursts and focal cortical dysplasia. Epilespia 1995;36:37± 40. [4] Komaki H, Sugai K, Sasaki M, Hashimoto T, Arai N, Takeda E, et al. Surgical treatment of a case of early infantile epileptic encephalopa-
[5]
[6] [7]
[8] [9]
[10]
thy with suppression-bursts associated with focal cortical dysplasia. Epilepsia 1999;40:365±369. Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E, Inoue H. Early-infantile epileptic encephalopathy with suppression-bursts. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, eds. Epileptic syndromes in infancy, childhood and adolescence, 2nd edn. London: John Libbey, 1992. pp. 25±34. Robain O, Dulac O. Early epileptic encephalopathy with suppression bursts and olivary-dentate dysplasia. Neuropediatrics 1992;23:162± 164. Vigevano F, Fusco L, Granata T, Fariello G, Di Rocco C, Cusmai R. Hemimegalencephaly: clinical and EEG characteristics. In: Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin BG, Pfanner P, eds. Dysplasias of cerebral cortex and epilepsy, Philadelphia: LippincottRaven, 1996. pp. 285±294. Ohtsuka Y, Ohno S, Oka E. Electroclinical characteristics of hemimegalencephaly. Pediatr Neurol 1999;20:390±393. Palmini A, Gambardella A, Andermann F, Dubeau F, da Costa JC, Olivier A, et al. Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results. Ann Neurol 1995;37:476±487. Gambardella A, Palmini A, Andermann F, Dubeau F, da Costa JC, Quesney LF, et al. Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy. Electroenceph Clin Neurophysiol 1996;98:243±249.
Case report
www.elsevier.com/locate/braindev
Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia Yoko Ohtsuka*, Masahiro Sato, Satoshi Sanada, Harumi Yoshinaga, Eiji Oka Department of Child Neurology, Okayama University Medical School, 2-5-1, Shikatacho, Okayama, Japan Received 3 September 1999; received in revised form 10 December 1999; accepted 13 December 1999
Abstract We report on a patient with early-onset spasms in series and partial seizures associated with focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy. These electroclinical characteristics suggested a diagnosis of Ohtahara syndrome, but the EEG ®ndings were atypical because of the lack of suppression-burst patterns during wakefulness. In addition, the patient did not have severe psychomotor retardation. With high-dose pyridoxal phosphate therapy, seizures were suppressed and suppression-burst patterns disappeared at 2 months of age. Focal motor seizures recurred later and they often evolved into epilepsia partialis continua. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEGs have several different etiologies, and these patients should be categorized according to their etiology in addition to their syndromic diagnosis. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Focal cortical dysplasia; Suppression-burst pattern; Spasms; Ohtahara syndrome; Early-infantile epileptic encephalopathy with suppression bursts
1. Introduction Some patients with focal cortical dysplasia show earlyonset spasms in series often associated with partial seizures [1,2]. When the EEGs of these patients reveal suppressionburst patterns, they might be diagnosed as having early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome) [3,4]. On the other hand, some cases of early myoclonic encephalopathy, early-onset West syndrome or localized brain malformations, such as hemimegalencephaly, share some ®ndings with cases of Ohtahara syndrome [5]. Thus, the boundaries of Ohtahara syndrome are not necessarily clear even though it is a clearly de®ned electroclinical entity [5]. Herein we report on and discuss a patient with early-onset intractable seizures and focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy.
2. Case report The patient is a 6-year 5-month-old boy. At 2 weeks after birth he began to have spasms in series which looked symmetrical. In addition, focal clonic convulsions involving the left corner of the mouth, the left eyelid and the left arm * Corresponding author. Tel.: 181-86-223-7151; fax: 181-86-2357377.
lasting several seconds to several dozens of seconds began to occur. He was referred to us at 1 month 21 days of age after having been placed on a therapy of 30 mg of phenytoin, 150 mg of valproate and 150 mg of pyridoxal phosphate daily. The EEG on admission showed unilateral suppression-burst patterns on the right side during sleep (Fig. 1). During wakefulness, EEGs showed a basic pattern of asymmetry with more slow waves in the right hemisphere, and multifocal spikes and multifocal spike-waves were observed mainly in the right central region without suppression-burst patterns. Simultaneous video-EEG-EMG polygraphic recordings revealed three types of seizures: a partial seizure followed by spasms in series; a partial seizure followed by spasms in series interspersed with several partial seizures; and spasms in series only. No myoclonus were detected by means of long-term simultaneous video-EEG-EMG polygraphic recordings. At 2 months 2 weeks of age all types of seizures were suppressed by increasing the dosage of pyridoxal phosphate to 360 mg/day. His EEGs also improved dramatically, and suppression-burst patterns disappeared. The patient was free from seizures on the monotherapy of pyridoxal phosphate until one year of age when focal clonic convulsions involving the left upper limb recurred. These focal motor seizures often evolved into epilepsia partialis continua (EPC). Interictal EEGs showed frequent 1.5±2 Hz slow spike-waves in the right frontal-central region in addi-
0387-7604/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S 0387-760 4(00)00090-5
136
Y. Ohtsuka et al. / Brain & Development 22 (2000) 135±138
Fig. 1. Interictal EEG at 1 month of age. During sleep unilateral suppression-burst patterns are observed on the right hemisphere. Calibration: 50 mV, 1 s.
tion to multifocal spikes/spike-waves and infrequent diffuse spike-waves and diffuse slow spike-waves. Ictal EEGs of focal motor seizures revealed 2.5±3 Hz spike-wave complexes in the right frontal-central region. An MRI at 1
year 3 months of age clearly revealed focal cortical dysplasia in the right frontal region (Fig. 2). An interictal SPECT with 99mTc-HMPAO revealed hypoperfusion in the same region. Proton magnetic resonance spectroscopic imaging
Fig. 2. Sagittal and axial MRI scans [3D MP±RAGE:TR(ms)/TE(ms)/TI(ms)/¯ip angle(8) 10/4/300/10] at 2 years 2 month of age shows a focal cortical dysplasia in the right frontal lobe in which the increased thickness of the cortex and widened cerebral sulci are visible (arrow heads).
Y. Ohtsuka et al. / Brain & Development 22 (2000) 135±138
( 1H-MRSI) showed a decrease in the N-acetylaspartate/ creatine (NAA/Cr) resonance intensity ratio in the right frontal lesion compared with the corresponding region in the left frontal lobe (1.95 in the right frontal lobe; 2.89 in the left frontal lobe). At 1 year 11 months of age, he began to have complex partial seizures, and at 2 years 1 month of age, these evolved into status epilepticus. Conversely, the focal motor seizures disappeared. Drip infusion of lidocaine (4 mg/kg per h) suppressed the complex partial status epilepticus. Five months later, focal motor seizures and EPC recurred. In spite of the persistence of seizures and the deterioration of the EEG ®ndings, his mental functions gradually developed. He started walking at 1 year 6 months of age, and saying meaningful words at 2 years 3 months of age. His developmental quotient as assessed by Enjoji Developmental Scales, was 57 at the age of 6 years 5 months. At 6 months of age, mild paresis of the left upper limb was noted. At 4 years 1 month of age, he underwent subpial transection of the right frontal lobe. The frequency of seizures gradually decreased after the surgery. He has had several focal motor seizures per week without EPC for the previous 6 months. His recent EEGs showed continuous epileptic discharges in the right frontal region without generalization of focal epileptic discharges (Fig. 3).
3. Discussion During the ®rst 2 months of this patient's life, his EEGs
Fig. 3. Interictal EEG during drowsy state at 6 years 5 months of age. Continuous spikes are observed on the right frontal region without generalization both during waking and sleeping states. Calibration: 50 mV, 1 s.
137
showed suppression-burst patterns only during sleep. In typical cases of Ohtahara syndrome, suppression-burst patterns appear both during waking and sleeping states [5]. It is speculated that suppression-burst patterns are caused by a subcortical-cortical regulation disorder, which is also associated with severe dysfunction of the cortex [5]. If this dysfunction is very severe, suppression-burst patterns appear both during waking and sleeping states. However, if this dysfunction is not very severe, suppression-burst patterns might be observed only during sleep. Thus, it is likely that the mode of appearance of suppression-burst patterns depends on the condition of the cortex. In this patient, the function of other cortical areas seems to be preserved relatively well because he does not suffer from severe psychomotor retardation and MRI ®ndings are almost normal for other cortical areas. Regarding the relationship between brain malformations such as focal cortical dysplasia and suppression-burst patterns on EEGs, it has been reported that a patient with olivary-dentate dysplasia showed early-onset partial seizures associated with suppression-burst patterns only during sleep on EEGs [6]. It is also well known that unilateral suppression-burst patterns are observed in hemimegalencephaly mostly during the ®rst few months after birth [7]. Moreover, some patients with hemimegalencephaly show early-onset partial seizures associated with suppression-burst patterns only during sleep [8]. These patients cannot be classi®ed as suffering from Ohtahara syndrome in the narrow sense because of the lack of tonic spasms and suppression-burst patterns during wakefulness. However, the diagnosis of Ohtahara syndrome is justi®ed if patients with hemimegalencephaly show early onset spasms in series and suppression-burst patterns on EEG both during waking and sleeping states [5,8]. Regarding the diagnosis of the patient in this report, in addition to his atypical EEG ®ndings, he has relatively favorable mental and motor development, compared with typical cases of Ohtahara syndrome. In conclusion, the diagnosis of Ohtahara syndrome is not justi®ed for this patient. However, the fact that there are some cases of Ohtahara syndrome associated with localized brain malformations, such as hemimegalencephaly and focal cortical dysplasia, and the similarity in electroclinical ®ndings between this case and some of the other cases mentioned herein may indicate that they share some of the same pathophysiological mechanisms. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEG have several different etiologies [3±8], and they should be categorized according to their etiology in addition to their syndromic diagnosis. Characteristic continuous or recurrent epileptic discharges on electrocorticograms [9] and rhythmic epileptiform discharges on scalp EEGs [10] have been reported in patients with focal cortical dysplasia and intractable epilepsy. However, changes in EEG ®ndings with age in these patients have not been clari®ed. EEGs of our patient
138
Y. Ohtsuka et al. / Brain & Development 22 (2000) 135±138
showed the characteristic change from unilateral suppression-burst patterns into continuous epileptic discharges in the region corresponding to the focal cortical dysplasia with increasing age. In order to use EEGs more speci®cally in the diagnosis of brain malformations, more detailed studies on age-dependent changes in EEG abnormalities are needed. References [1] Dulac O, Pinard JM, Plouin P. Infantile spasms associated with cortical dysplasia and tuberous sclerosis. In: Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin BG, Pfanner P, eds. Dysplasias of cerebral cortex and epilepsy, Philadelphia: Lippincott-Raven, 1996. pp. 217±225. [2] Ohtsuka Y. West syndrome and its related epileptic syndromes. Epilepsia 1998;39(Suppl 5):30±37. [3] Pedespan JM, Loiseau H, Vital A, Marchal C, Fontan D, Rougier A. Surgical treatment of an early epileptic encephalopathy with suppression-bursts and focal cortical dysplasia. Epilespia 1995;36:37± 40. [4] Komaki H, Sugai K, Sasaki M, Hashimoto T, Arai N, Takeda E, et al. Surgical treatment of a case of early infantile epileptic encephalopa-
[5]
[6] [7]
[8] [9]
[10]
thy with suppression-bursts associated with focal cortical dysplasia. Epilepsia 1999;40:365±369. Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E, Inoue H. Early-infantile epileptic encephalopathy with suppression-bursts. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, eds. Epileptic syndromes in infancy, childhood and adolescence, 2nd edn. London: John Libbey, 1992. pp. 25±34. Robain O, Dulac O. Early epileptic encephalopathy with suppression bursts and olivary-dentate dysplasia. Neuropediatrics 1992;23:162± 164. Vigevano F, Fusco L, Granata T, Fariello G, Di Rocco C, Cusmai R. Hemimegalencephaly: clinical and EEG characteristics. In: Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin BG, Pfanner P, eds. Dysplasias of cerebral cortex and epilepsy, Philadelphia: LippincottRaven, 1996. pp. 285±294. Ohtsuka Y, Ohno S, Oka E. Electroclinical characteristics of hemimegalencephaly. Pediatr Neurol 1999;20:390±393. Palmini A, Gambardella A, Andermann F, Dubeau F, da Costa JC, Olivier A, et al. Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results. Ann Neurol 1995;37:476±487. Gambardella A, Palmini A, Andermann F, Dubeau F, da Costa JC, Quesney LF, et al. Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy. Electroenceph Clin Neurophysiol 1996;98:243±249.