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A case of malignant migrating partial seizures in infancy as a continuum of infantile epileptic encephalopathy
Brain & Development 34 (2012) 768–772 www.elsevier.com/locate/braindev
Case report
A case of malignant migrating partial seizures in infancy as a continuum of infantile epileptic encephalopathy Eun Hye Lee a, Mi-Sun Yum b, Min-Hee Jeong c, Kyung Yeon Lee d, Tae-Sung Ko b,⇑ b
a Department of Pediatrics, College of Medicine, Kyung Hee University, Seoul, Republic of Korea Department of Pediatrics, Asan Medical Center, Children’s Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea c Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea d Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
Received 26 August 2011; received in revised form 28 November 2011; accepted 28 November 2011
Abstract The syndrome of malignant migrating partial seizures in infancy (MMPSI) is characterized by onset before the age of 6 months, nearly continuous electrographic seizures involving multiple independent areas of onset in both hemispheres, and poor developmental outcome. This report presents a case involving a patient with MMPSI, who later developed West syndrome. At the age of 2 months old, he showed multifocal partial seizures, which were refractory to antiepileptic drugs. His electroencephalogram (EEG) revealed characteristic migrating multifocal epileptiform activities and neuroimaging finding was normal. The focal seizures were refractory to antiepileptic drugs and ketogenic diet. When he was 9 months old, epilepic spasms were observed with hypsarrhythmia on EEG. He also showed severe developmental delay. MMPSI may be a continuum of infantile epileptic encephalpathy and could evolve to West syndrome. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Migrating partial seizure; Epileptic encephalopathy; Infantile spasms
1. Introduction Malignant migrating partial seizures in infancy (MMPSI) is a rare, early onset epilepsy syndrome, which is known to be associated with intractable seizures and developmental arrest. Sixteen years ago, Coppola et al. [1] first described a previously unreported epileptic syndrome in 14 infants with seizure onset during the first year of life, focal motor seizures at onset, nearly continuous multifocal seizure involving both hemispheres, progression through a period of intractable seizures,
and subsequent severe psychomotor retardation. Characteristically, focal electroencephalographic discharges migrate from one brain region to another, arising from different areas of the same or the opposite hemisphere. Although cases are identified in various countries to date [2–9], only few reports described its evolution to West syndrome. Here we report on an infant who first presented with malignant migrating partial seizures in infancy, who later developed West syndrome. 2. Case report
⇑ Corresponding author. Address: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine 388-1, Poongnap-dong, Songpa-ku, Seoul 138 736, Republic of Korea. Tel.: +82 2 3010 3388; fax: +82 2 473 3725. E-mail address: [email protected] (T.-S. Ko).
The patient was the second born infant after a normal pregnancy and delivery to non-consanguineous parents. He was born at 40 + 1 weeks of gestation with a birth weight of 4000 g. At 3 months of age, he was admitted
0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.11.011
E.H. Lee et al. / Brain & Development 34 (2012) 768–772
769
Fig. 1. Electroencephalogram showing seizures originating from the left temporo-parietal region (A, B) and another one from the right parietooccipital region (C). After 30 s, ictal discharges shift to the left parieto-occipital region (D).
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E.H. Lee et al. / Brain & Development 34 (2012) 768–772
Fig 1. (continued)
E.H. Lee et al. / Brain & Development 34 (2012) 768–772
771
Fig. 2. Electroencephalogram recorded at 9 months-old showed multifocal spike discharges with high amplitude background activity (hypsarrhythmia).
to our hospital due to intractable partial seizures. His seizures were characterized by lateral deviation of the head and eyes, tonic elevation of one or both limbs on one side, alternatively, clonic twiches of the eyelieds and flushing of the face. The seizures lasted between 1 and 20 min, ocurring more than 10 times a day in clusters. On admission to our hospital, his weight was 8.3 kg (90–95th percentile), height 67.3 cm (90–95th percentile), and head circumference was 42.5 cm (75th percentile). His neurologic examination and pychomotor development were unremarkable at that time. Biochemical investigations, extensive metabolic screening tests remained negative. Brain magnetic resonance imging (MRI) was normal. The electroencephalogram (EEG) showed frequent rhythmic sharp wave discharges starting from the left temporo-parietal region, and spreading to the right pareito-occipital region (Fig. 1). Various antiepileptic drugs (phenobarbital, valproate, phenytoin, topiramate, pyridoxine, levetiracetam, vigabatrin, and clobazam) failed to control his frequent partial seizures. At the age of 4 months, ketogenic diet was tried, and seizure frequency decreased to two to three times
per day. Despite continuing the antiepileptic drug medication and ketogenic diet, epileptic spasms began to occur at the age of 9 months. EEG performed at that time showed a modified hypsarrhythmia pattern (Fig. 2). At the last evaluation of 14 months, his head circumference had dropped to the third percentile (43.5 cm) with normal weight and height for his age. He has shown severe neurologic impairment with poor visual following and generalized hypotonia. He is now on nasogastric tube feeding due to difficulty with swallowing, and he cannot reach for objects. 3. Discussion MMPSI is a rare, age-specific epileptic encephalopathy with intractable seizures and developmental arrest [1,5]. The patient in this report fulfills the diagnostic criteria of MMPSI described by Coppola et al. [1]: onset before 6 months of age, migrating focal motor seizures at onset, multifocal seizures intractable to conventional antiepileptic drugs, and severe psychomotor delay. Our patient had focal migrating seizures at the onset of dis-
772
E.H. Lee et al. / Brain & Development 34 (2012) 768–772
ease, and characterfully began to have epileptic spasms at the age of 9 months. The EEG at this time showed modified hypsarrhythmia. Although several studies have reported longditudinal follow-up data on this syndrome, few cases involving evolution to other age-related epileptic encephalopathy have been reported [1,9,10]. Only two patients in the entire reported series exhibited epileptic spasms. One patient had epileptic spasms associated with a focal discharge beginning at the age of 9 months, which persisted until the age of 18 months[1]. The other patient was an infant with Aicardi syndrome. In the second report, epileptic spasms were observed at the age of 6 months without the typical hypsarrhythmic pattern [9]. Thus, our patient represents the first case with epileptic spasms and hypsarrhythmia on EEG. This condition is comparable to the other neonatal epileptic encephalopathies: early infantile epileptic encephalopathy (EIEE) and early myoclonic encephalopathy (EME). It shares some common features with these two syndromes (early onset, intractability and grave prognosis) [11,12]. Along with these findings, our case report support the hypothesis that they may be a spectrum of age-related epileptic encephalopathy sharing a common mechanism. On the other hand, MMPSI has distinct EEG features from these two syndromes. The focal migrating epileptic discharges in this syndrome are belived due to diffuse cortical hyperexcitability, while brain stem is assumed to be involved in pathogenesis of the two neonatal epileptic encepahalopathies and epileptic spasms [8,12]. We suggest that a time-specific maturation pattern of the developing brain may play an important role in determine different electroclinical presentations in these age- related epileptic syndromes. In addition, this case inform us that West syndrome is not limitied in specific conditions but represent an age specific “common pathway” in various epileptic conditions with different etiologies. It is well known that West syndrome has heterogeneous etiologies such as neonatal asphyxia, brain malformation, inborn errors of metabolism, and tubersous sclerosis [13]. Further studies are needed to identify the precise mechanism of these age-related epileptic
encephalopathies and factors influencing the evolution within these syndromes. We report here on the first Korean patient with MMPSI. Our patient first presented with MMPSI and later evolved to West syndrome. This finding supports the hypothesis that this condition may be a continuum of infantile epileptic encephalopathy, probably sharing a common pathophysiology with maturation related hyperexcitability. References [1] Coppola G, Plouin P, Chiron C, Robain O, Dulac O. Migrating partial seizures in infancy: a malignant disorder with developmental arrest. Epilepsia 1995;36:1017–24. [2] Okuda K, Yasuhara A, Kamei A, Araki A, Kitamura N, Kobayashi Y. Successful control with bromide of two patients with malignant migrating partial seizures in infancy. Brain Dev 2000;22:56–9. [3] Wilmshurst JM, Appleton DB, Grattan-Smith PJ. Migrating partial seizures in infancy: two new cases. J Child Neurol 2000;15: 717–22. [4] Veneselli E, Perrone MV, Di Rocco M, Gaggero R, Biancheri R. Malignant migrating partial seizures in infancy. Epilepsy Res 2001;46:27–32. [5] Gross-Tsur V, Ben-Zeev B, Shalev RS. Malignant migrating partial seizures in infancy. Pediatr Neurol 2004;31:287–90. [6] Marsh E, Melamed SE, Barron T, Clancy RR. Migrating partial seizures in infancy: expanding the phenotype of a rare seizure syndrome. Epilepsia 2005;46:568–72. [7] Hmaimess G, Kadhim H, Nassogne MC, Bonnier C, van Rijckevorsel K. Levetiracetam in a neonate with malignant migrating partial seizures. Pediatr Neurol 2006;34:55–9. [8] Hahn A, Heckel M, Neubauer BA. Pronounced microcephaly in a patient with malignant migrating partial seizures in infancy. Epileptic Disord 2007;9:94–7. [9] Jocic-Jakubi B, Lagae L. Malignant migrating partial seizures in Aicardi syndrome. Dev Med Child Neurol 2008;50:790–2. [10] Caraballo RH, Fontana E, Darra F, Cassar L, Negrini F, Fiorini E, et al. Migrating focal seizures in infancy: analysis of the electroclinical patterns in 17 patients. J Child Neurol 2008;23:497–506. [11] Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special references to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res 2006;70S:S58–67. [12] Djukic A, Lado FA, Shinnar S, Moshe SL. Are myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independet each other? Epilepsy Res 2006;70S:S68–76. [13] Donat Jane F. Topical review article: the age-dependent epileptic encephalopathies. J Child Neurol 1992;7:7–21.
Case report
A case of malignant migrating partial seizures in infancy as a continuum of infantile epileptic encephalopathy Eun Hye Lee a, Mi-Sun Yum b, Min-Hee Jeong c, Kyung Yeon Lee d, Tae-Sung Ko b,⇑ b
a Department of Pediatrics, College of Medicine, Kyung Hee University, Seoul, Republic of Korea Department of Pediatrics, Asan Medical Center, Children’s Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea c Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea d Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
Received 26 August 2011; received in revised form 28 November 2011; accepted 28 November 2011
Abstract The syndrome of malignant migrating partial seizures in infancy (MMPSI) is characterized by onset before the age of 6 months, nearly continuous electrographic seizures involving multiple independent areas of onset in both hemispheres, and poor developmental outcome. This report presents a case involving a patient with MMPSI, who later developed West syndrome. At the age of 2 months old, he showed multifocal partial seizures, which were refractory to antiepileptic drugs. His electroencephalogram (EEG) revealed characteristic migrating multifocal epileptiform activities and neuroimaging finding was normal. The focal seizures were refractory to antiepileptic drugs and ketogenic diet. When he was 9 months old, epilepic spasms were observed with hypsarrhythmia on EEG. He also showed severe developmental delay. MMPSI may be a continuum of infantile epileptic encephalpathy and could evolve to West syndrome. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Migrating partial seizure; Epileptic encephalopathy; Infantile spasms
1. Introduction Malignant migrating partial seizures in infancy (MMPSI) is a rare, early onset epilepsy syndrome, which is known to be associated with intractable seizures and developmental arrest. Sixteen years ago, Coppola et al. [1] first described a previously unreported epileptic syndrome in 14 infants with seizure onset during the first year of life, focal motor seizures at onset, nearly continuous multifocal seizure involving both hemispheres, progression through a period of intractable seizures,
and subsequent severe psychomotor retardation. Characteristically, focal electroencephalographic discharges migrate from one brain region to another, arising from different areas of the same or the opposite hemisphere. Although cases are identified in various countries to date [2–9], only few reports described its evolution to West syndrome. Here we report on an infant who first presented with malignant migrating partial seizures in infancy, who later developed West syndrome. 2. Case report
⇑ Corresponding author. Address: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine 388-1, Poongnap-dong, Songpa-ku, Seoul 138 736, Republic of Korea. Tel.: +82 2 3010 3388; fax: +82 2 473 3725. E-mail address: [email protected] (T.-S. Ko).
The patient was the second born infant after a normal pregnancy and delivery to non-consanguineous parents. He was born at 40 + 1 weeks of gestation with a birth weight of 4000 g. At 3 months of age, he was admitted
0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.11.011
E.H. Lee et al. / Brain & Development 34 (2012) 768–772
769
Fig. 1. Electroencephalogram showing seizures originating from the left temporo-parietal region (A, B) and another one from the right parietooccipital region (C). After 30 s, ictal discharges shift to the left parieto-occipital region (D).
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E.H. Lee et al. / Brain & Development 34 (2012) 768–772
Fig 1. (continued)
E.H. Lee et al. / Brain & Development 34 (2012) 768–772
771
Fig. 2. Electroencephalogram recorded at 9 months-old showed multifocal spike discharges with high amplitude background activity (hypsarrhythmia).
to our hospital due to intractable partial seizures. His seizures were characterized by lateral deviation of the head and eyes, tonic elevation of one or both limbs on one side, alternatively, clonic twiches of the eyelieds and flushing of the face. The seizures lasted between 1 and 20 min, ocurring more than 10 times a day in clusters. On admission to our hospital, his weight was 8.3 kg (90–95th percentile), height 67.3 cm (90–95th percentile), and head circumference was 42.5 cm (75th percentile). His neurologic examination and pychomotor development were unremarkable at that time. Biochemical investigations, extensive metabolic screening tests remained negative. Brain magnetic resonance imging (MRI) was normal. The electroencephalogram (EEG) showed frequent rhythmic sharp wave discharges starting from the left temporo-parietal region, and spreading to the right pareito-occipital region (Fig. 1). Various antiepileptic drugs (phenobarbital, valproate, phenytoin, topiramate, pyridoxine, levetiracetam, vigabatrin, and clobazam) failed to control his frequent partial seizures. At the age of 4 months, ketogenic diet was tried, and seizure frequency decreased to two to three times
per day. Despite continuing the antiepileptic drug medication and ketogenic diet, epileptic spasms began to occur at the age of 9 months. EEG performed at that time showed a modified hypsarrhythmia pattern (Fig. 2). At the last evaluation of 14 months, his head circumference had dropped to the third percentile (43.5 cm) with normal weight and height for his age. He has shown severe neurologic impairment with poor visual following and generalized hypotonia. He is now on nasogastric tube feeding due to difficulty with swallowing, and he cannot reach for objects. 3. Discussion MMPSI is a rare, age-specific epileptic encephalopathy with intractable seizures and developmental arrest [1,5]. The patient in this report fulfills the diagnostic criteria of MMPSI described by Coppola et al. [1]: onset before 6 months of age, migrating focal motor seizures at onset, multifocal seizures intractable to conventional antiepileptic drugs, and severe psychomotor delay. Our patient had focal migrating seizures at the onset of dis-
772
E.H. Lee et al. / Brain & Development 34 (2012) 768–772
ease, and characterfully began to have epileptic spasms at the age of 9 months. The EEG at this time showed modified hypsarrhythmia. Although several studies have reported longditudinal follow-up data on this syndrome, few cases involving evolution to other age-related epileptic encephalopathy have been reported [1,9,10]. Only two patients in the entire reported series exhibited epileptic spasms. One patient had epileptic spasms associated with a focal discharge beginning at the age of 9 months, which persisted until the age of 18 months[1]. The other patient was an infant with Aicardi syndrome. In the second report, epileptic spasms were observed at the age of 6 months without the typical hypsarrhythmic pattern [9]. Thus, our patient represents the first case with epileptic spasms and hypsarrhythmia on EEG. This condition is comparable to the other neonatal epileptic encephalopathies: early infantile epileptic encephalopathy (EIEE) and early myoclonic encephalopathy (EME). It shares some common features with these two syndromes (early onset, intractability and grave prognosis) [11,12]. Along with these findings, our case report support the hypothesis that they may be a spectrum of age-related epileptic encephalopathy sharing a common mechanism. On the other hand, MMPSI has distinct EEG features from these two syndromes. The focal migrating epileptic discharges in this syndrome are belived due to diffuse cortical hyperexcitability, while brain stem is assumed to be involved in pathogenesis of the two neonatal epileptic encepahalopathies and epileptic spasms [8,12]. We suggest that a time-specific maturation pattern of the developing brain may play an important role in determine different electroclinical presentations in these age- related epileptic syndromes. In addition, this case inform us that West syndrome is not limitied in specific conditions but represent an age specific “common pathway” in various epileptic conditions with different etiologies. It is well known that West syndrome has heterogeneous etiologies such as neonatal asphyxia, brain malformation, inborn errors of metabolism, and tubersous sclerosis [13]. Further studies are needed to identify the precise mechanism of these age-related epileptic
encephalopathies and factors influencing the evolution within these syndromes. We report here on the first Korean patient with MMPSI. Our patient first presented with MMPSI and later evolved to West syndrome. This finding supports the hypothesis that this condition may be a continuum of infantile epileptic encephalopathy, probably sharing a common pathophysiology with maturation related hyperexcitability. References [1] Coppola G, Plouin P, Chiron C, Robain O, Dulac O. Migrating partial seizures in infancy: a malignant disorder with developmental arrest. Epilepsia 1995;36:1017–24. [2] Okuda K, Yasuhara A, Kamei A, Araki A, Kitamura N, Kobayashi Y. Successful control with bromide of two patients with malignant migrating partial seizures in infancy. Brain Dev 2000;22:56–9. [3] Wilmshurst JM, Appleton DB, Grattan-Smith PJ. Migrating partial seizures in infancy: two new cases. J Child Neurol 2000;15: 717–22. [4] Veneselli E, Perrone MV, Di Rocco M, Gaggero R, Biancheri R. Malignant migrating partial seizures in infancy. Epilepsy Res 2001;46:27–32. [5] Gross-Tsur V, Ben-Zeev B, Shalev RS. Malignant migrating partial seizures in infancy. Pediatr Neurol 2004;31:287–90. [6] Marsh E, Melamed SE, Barron T, Clancy RR. Migrating partial seizures in infancy: expanding the phenotype of a rare seizure syndrome. Epilepsia 2005;46:568–72. [7] Hmaimess G, Kadhim H, Nassogne MC, Bonnier C, van Rijckevorsel K. Levetiracetam in a neonate with malignant migrating partial seizures. Pediatr Neurol 2006;34:55–9. [8] Hahn A, Heckel M, Neubauer BA. Pronounced microcephaly in a patient with malignant migrating partial seizures in infancy. Epileptic Disord 2007;9:94–7. [9] Jocic-Jakubi B, Lagae L. Malignant migrating partial seizures in Aicardi syndrome. Dev Med Child Neurol 2008;50:790–2. [10] Caraballo RH, Fontana E, Darra F, Cassar L, Negrini F, Fiorini E, et al. Migrating focal seizures in infancy: analysis of the electroclinical patterns in 17 patients. J Child Neurol 2008;23:497–506. [11] Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special references to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res 2006;70S:S58–67. [12] Djukic A, Lado FA, Shinnar S, Moshe SL. Are myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independet each other? Epilepsy Res 2006;70S:S68–76. [13] Donat Jane F. Topical review article: the age-dependent epileptic encephalopathies. J Child Neurol 1992;7:7–21.