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Regional specificity of localized cortical lesions in West syndrome
Regional Specificity of Localized Cortical Lesions in West Syndrome Shin-Ichiro Hamano, MD*, Manabu Tanaka, MD*, Sakiko Kawasaki, MD,*† Takahiro Nara, MD*, Hideki Horita, MD†, Yoshikatsu Eto, MD†, and Saburo Kohno, MD* West syndrome, although classified as a generalized epilepsy, is associated with localized cerebral lesions in some cases. However, similar localized cortical abnormalities usually can result in partial epilepsy, instead of West syndrome. We performed this study to determine the additional factors that result in West syndrome instead of partial epilepsy in patients with localized cerebral lesions. We reviewed the pathologic features, topographic localization, and side of unilaterally defined cerebral lesions in relation to the seizure types in 39 epileptic patients, including five patients who presented with West syndrome. The lesions of all five patients with West syndrome involved the temporal or occipital lobes (or both). Among the nine with an occipital lesion, four had West syndrome. In the 19 with a temporal lesion, three had West syndrome. However, in the 16 patients with a frontal lesion, none exhibited epileptic spasms. In four of the five with West syndrome the lesions were on the right side; 23 had lesions on the right, 16 had them on the left. Temporooccipital lesions and lesions on the right were related to the genesis of West syndrome, which would be in close correlation with normal brain maturation. © 2000 by Elsevier Science Inc. All rights reserved. Hamano S-I, Tanaka M, Kawasaki S, Nara T, Horita H, Eto Y, Kohno S. Regional specificity of localized cortical lesions in West syndrome. Pediatr Neurol 2000;23: 219-224.
Introduction In West syndrome, although classified as a generalized epilepsy, focal ictal features are not uncommon [1,2]. Some previously reported patients had West syndrome associated with distinct localized cerebral lesions in neuroradiologic studies [2-15]. Some of those patients became
From the *Division of Neurology; Saitama Children’s Medical Center; Saitama; and †Department of Pediatrics; Jikei University School of Medicine; Tokyo, Japan.
© 2000 by Elsevier Science Inc. All rights reserved. PII S0887-8994(00)00173-9 ● 0887-8994/00/$20.00
seizure free and had good developmental outcomes after resection of the localized lesions. Chugani et al. [16] reported that the patients with infantile spasms and normal magnetic resonance imaging (MRI) findings who underwent surgical resection of cerebral lesions with abnormal features on positron emission tomography (PET), exhibited good outcomes in seizure control and development. These investigators proposed the hypothesis of a corticalsubcortical interaction through the raphe nuclei as the pathophysiology of West syndrome as being more emphasized in the role of cortical lesions than previously postulated [16-18]. However, similar localized cortical abnormalities from the neonatal period usually can result in partial epilepsy instead of West syndrome. Additional factors to induce or facilitate West syndrome must exist, and those factors might include features of the cortical lesions, such as the pathologic findings, topographic localization, and side, and may be crucial in the pathophysiology of West syndrome. To determine whether the pathologic features, topographic localization, and side of the cerebral lesions are associated with West syndrome, we studied these features in relation to the seizure types and the findings of electroencephalography (EEG) in 39 epileptic patients with an isolated lesion, including five patients who presented with West syndrome. Material and Methods From all patients with epilepsy referred to the Saitama Children’s Medical Center between April 1983 and September 1998, we selected those satisfying the following criteria: an isolated lesion confined to a unilateral cerebral hemisphere and not extending over the whole hemisphere on MRI studies (1.5-T Siemens Magnetom), including T1weighted (TR-540-600 ms, TE-15 ms), T2-weighted (TR-300-3,500 ms, TE-90-93 ms), and proton density-weighted (TR-3,000-3500 ms, TE10-19 ms) images in the axial, coronal, and sagittal views, and duration of follow-up more than 3 years. We excluded patients with phacomatosis, mesial temporal sclerosis, an arachnoid cyst, a lesion presumed to be an
Communications should be addressed to: Dr. Hamano; Division of Neurology; Saitama Children’s Medical Center; 2100 Magome, Iwatsuki, Saitama 339-8551 Japan. Received January 10, 2000; accepted April 15, 2000.
Hamano et al: West Syndrome With Focal Lesions 219
Table 1.
Pt. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
Clinical characteristics of patients
Sex
Onset Age of Seizure
Age at Evaluation
Male Female Male Female Male Female Male Male Female Female Male Male Female Male Female Female Male Female Male Female Male Male Female Male Male Male Male Male Male Male Male Female Female Female Male Female Male Male Female
10 yr 6 mo 1 mo 8 yr 8 mo 7 mo 2 yr 2 mo 2 yr 6 mo 3 yr 9 mo 1 yr 3 mo 1 yr 3 mo 7 yr 3 mo 2 yr 6 mo 8 mo 5 yr 1 mo 5 yr 9 mo 8 yr 5 mo 4 yr 10 yr 7 mo 7 yr 5 mo 3 yr 9 mo 13 yr 10 mo 11 yr 2 yr 1 mo 10 yr 8 mo 11 yr 8 mo 1 yr 5 mo 14 yr 10 mo 3 yr 2 mo 1 yr 9 mo 3 yr 8 mo 2 yr 11 mo 2 yr 2 mo 4 mo 7 yr 8 mo 4 mo 7 mo 10 yr 5 mo 3 mo 5 mo
14 yr 3 mo 13 yr 6 mo 17 yr 6 mo 15 yr 8 yr 3 mo 5 yr 6 mo 10 yr 7 mo 9 yr 11 mo 6 yr 6 mo 20 yr 2 mo 7 yr 9 mo 3 yr 8 mo 9 yr 5 mo 12 yr 13 yr 7 mo 7 yr 21 yr 6 mo 12 yr 6 mo 14 yr 5 mo 21 yr 6 mo 16 yr 11 mo 12 yr 9 mo 21 yr 6 mo 20 yr 11 mo 14 yr 10 mo 10 yr 9 mo 19 yr 5 mo 13 yr 8 mo 10 yr 6 mo 7 yr 7 mo 6 yr 9 mo 5 yr 9 mo 9 yr 6 mo 19 yr 9 mo 4 yr 3 mo 6 yr 11 mo 13 yr 8 mo 5 yr 11 mo 21 yr 1 mo
Abbreviations: aT ⫽ Anteriotemporal C ⫽ Central F ⫽ Frontal Fp ⫽ Frontpolar L ⫽ Left mT ⫽ Midtemporal
Lesions Type on MRI Studies Tumorous lesion Tumorous lesion Cortical heterotopia Focal atrophy Spot lesion in white Focal atrophy Spot lesion in white Tumorous lesion Tumorous lesion Tumorous lesion Cortical dysplasia Spot lesion in white Tumorous lesion Focal atrophy Focal atrophy Porencephary Spot lesion in white Focal atrophy Spot lesion in white Focal atrophy Focal atrophy Spot lesion in white Porencephary Porencephary Tumorous lesion Tumorous lesion Tumorous lesion Focal atrophy Focal atrophy Focal atrophy Cortical dysplasia Porencephary Focal atrophy Focal atrophy Cortical heterotopia Porencephary Focal atrophy Cortical dysplasia Porencephary
matter
⫹(L-FFp) ⫹(L-F) ⫹(L-F) ⫹(L-F) ⫹(R-F) ⫹(L-C) ⫹(L-F) ⫹(R-FC)
⫹(L-O) ⫹(L-O)
⫹(R-CF)
⫹(R-O)
⫹(R-F,O) ⫹(R-F) ⫹(R-F,O)
⫹(L-FFp) ⫹(L-FC)
matter
matter
⫹(R-F) ⫹(R-F) ⫹(R-FCP) ⫹(L-PO) ⫹(G) ⫹(R-PC)
matter
matter
⫹(R-F) ⫹(R-mTP) ⫹(L-aT) ⫹(R-aT) ⫹(L-mT) ⫹(L-aTmT) ⫹(R-pTP) ⫹(R-OpT) ⫹(R-O) ⫹(L-OpT) ⫹(R-O) ⫹(L-O) ⫹(R-O)
⫹(L-F) ⫹(L-F) ⫹(R-F,O) ⫹(R-F,O)
⫹(L-PC)
⫹(R-F,O) ⫹(R-aT)
⫹(L-F,O) ⫹(L-F,P)
⫹(R-FFp) ⫹(R-F) ⫹(L-O,Fp) ⫹(R-F) ⫹(L-FC) ⫹(L-FCP) ⫹(R-FFp) ⫹(R-CP) ⫹(L-FCP) ⫹(R-CP) ⫹(L-F)
⫹(R-mT,F)
⫹(L-O) ⫹(L-OP,F) ⫹(R-O,F) ⫹(L-FFP,O)
O ⫽ Occipital P ⫽ Parietal Pt. No. ⫽ Patient number pT ⫽ Posteriotemporal R ⫽ Right
insult after a perinatal period, or a lesion exhibiting progressive changes on MRI during a follow-up period. The medical records of these patients were reviewed for the age at onset of epilepsy, seizure types, interictal EEG recordings, including, if applicable, ictal recordings, neurologic status, and long-term outcome of epilepsy. Thirty-nine patients met these criteria. The patients (23 males and 16 females) ranged in age from 3 years, 8 months to 21 years, 6 months (mean ⫽ 12 years, 6 months) at the time of the evaluation. The follow-up periods ranged from 3 to 13.4 years (mean ⫽ 6.9).
Results The average age at the onset of epilepsy was 4 years, 9 months (range ⫽ 1 month to 14 years, 10 months).
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Complications included mental retardation in 18 patients, hemiplegia in 11 patients, behavioral disorders in one patient, and tics in one patient (Table 1). MRI findings conformed to six categories: focal atrophy in 13 patients; a tumorous lesion in nine patients; porencephaly in six patients; a spot lesion in the white matter that was a small oval lesion with low intensity on T1-weighted and high intensity on T2-weighted images and probably indicated gliosis in the white matter in six patients; cortical dysplasia in three patients, and cortical heterotopia in two patients. Of these patients, Patient 38 underwent lesionectomy, and the lesion was pathologically diagnosed as focal
cortical dysplasia. The other patients had not been treated surgically. The presumed diagnosis of patients having a tumorous lesion, on the basis of MRI and computed tomography, was as follows: astrocytoma in Patients 1, 8, 9, 13, and 27; ganglioglioma in Patients 25 and 26; cavernous hemangioma in Patient 2; and dysembryoplastic neuroepithelial tumor in Patient 10. All patients presented with a partial seizure; 15 patients also had secondarily generalized seizures (Table 1 and Table 2). Epileptic spasms preceded or followed partial seizures in five patients (Patients 24, 33, 35, 38, and 39) manifesting hypsarrhythmia who were diagnosed with West syndrome; three of them were male. In Patient 38, ocular deviation to the left proceeded to epileptic spasms, and the seizures were intractable to antiepileptic drugs and adrenocorticotropin. His development was severely retarded, and he could neither sit alone nor speak a word at 4 years of age. After the lesionectomy at 4 years, 7 months of age, his development improved slightly, and seizures were not observed for 9 months. His seizures recurred daily from 5 years, 4 months of age. The partial seizures of the other patients with West syndrome followed epileptic spasms, which disappeared after administration of adrenocorticotropin or antiepileptic drugs. The partial seizures of the four patients with West syndrome occurred at the age of 13 years, 5 months in Patient 24, 1 year, 1 month in Patient 33, 2 years, 10 months in Patient 35, and 8 years, 11 months Patient 39. The partial seizures of Patients 24 and 39 had been controlled through antiepileptic drugs for the previous 2 years. The partial seizures of Patient 33 occurred monthly; those of patients 35 and 38 occurred daily. Ictal EEGs recorded in Patients 3 and 38 revealed that the initial discharge on the onset of partial seizures corresponded with the lesions detected on MRI. In the 27 patients, including Patients 3 and 38, the interictal discharges corresponded to the lesions. Five patients had no paroxysmal discharge on the interictal EEG recording through the follow-up period. Paroxysmal discharges in the other ipsilateral regions were less often observed in the patients with a frontal lesion; they were more common in the patients with a lesion in other regions. Contralateral paroxysmal discharges to the lesions were observed in 15 patients independently of the localization of the lesions. Table 2 presents the topographic localization of the lesions of the 39 patients. Of all 39 patients, 16 patients had lesions in the frontal lobe, 11 patients had lesions in the parietal lobe, 19 patients had lesions in the temporal lobe, and nine patients had lesions in the occipital lobe. The lesions of all five patients with West syndrome were in the temporal or occipital lobes (or both). Among the nine patients with a lesion in the occipital lobe, four patients were diagnosed with West syndrome. In the 19 patients with a lesion in the temporal lobe, three patients had West syndrome. However, in the 15 patients with a lesion in the frontal or parietal lobes (or both) without involvement of the temporal and occipital lobes, none
Table 2.
Topography of lesions and type of seizures
, partial seizures only. , partial seizures and secondarily generalized seizures. , epileptic spasms with or without partial seizures.
exhibited epileptic spasms. The side of the brain with the lesion was the right in the four patients with West syndrome; 23 patients had the lesion on the right side and 16 patients on the left side. Discussion Although this is a relatively small series of 39 epileptic patients with a varied localized cerebral lesion, some particular features are apparent. West syndrome was more common in the patients with a temporo-occipital lesion than in those with a frontal lesion and occurred more often in patients with lesions localized on the right than the left hemisphere. West syndrome associated with a defined localized lesion such as a tumor or porencephaly, has been
Hamano et al: West Syndrome With Focal Lesions 221
Table 3.
Topography of lesions of West syndrome with localized lesions previously reported
previously reported. Table 3 presents the topographic localization and diagnosis of the lesion of the patients with West syndrome who had been previously reported [2-12, 14,15]. In 17 patients, five had a lesion without obvious involvement of the cerebral cortex. The lesions involved
the basal ganglia, lateral ventricle, optic nerve, thalamus, and hypothalamus [3-5,12,15]. The data in Table 3 revealed that temporal involvement was common in West syndrome associated with localized cerebral lesions and that lesions were more often on the right than the left
Table 4. Topography of lesions on positron emission tomography study of West syndrome by Chugani et al. [16]
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hemisphere. Chugani et al. [16] reported 23 patients with intractable infantile spasms, including 13 patients with normal MRI findings, who had a good outcome after resection of the lesions. The patients were evaluated by PET studies. The lesions in seven patients extended to the whole cerebral hemisphere or were bilateral. Among the other 16 patients, only two patients had frontal lesions. However, 15 of the 16 patients had lesions that involved a temporal lobe, 13 patients had involvement in an occipital lobe, and 14 patients exhibited an abnormality in a parietal lobe on PET studies (Table 4). Although the difference in the side was not significant, temporo-occipital involvement was common in the study by Chugani et al. [16]. All but three patients had a good outcome after resection of these lesions, as evaluated by PET, and the resected lesions exhibited pathologic abnormalities [16]. It is likely that the lesions revealed by PET were not transient abnormalities and that they were the crucial lesions in terms of the epileptic spasms, irrespective of the normal MRI findings. The study of 24-hour ambulatory EEG monitoring in infantile spasms accompanied with partial seizures revealed that partial seizures originated from the temporal and rolandic regions and originated more often from the right hemisphere in most cases [19]. Koo and Hwang [20] studied the onset age of infantile spasms in 93 patients with focal cerebral findings, including functional lesions detected by PET, single positron emission tomography, and EEG. Their conclusions were that occipital lesions were associated with the earliest age of onset of spasms, and that frontal lesions were rare and associated with the latest onset of spasms. These results are substantially consistent with our results. West syndrome is an age-dependent epilepsy occurring in infancy. The high incidence of West syndrome with partial seizures that originate from a (centro-)temporooccipital region could be a result of normal brain maturation. Myelination in normal brain develops from the central regions toward each pole of the cerebral lobes, and occipital poles myelinate before the fronto-temporal poles [21]. Kato and Okuyama [22] reported that the distribution of cerebral blood flow began from the cerebellums, thalamus, basal ganglia, and central regions. Thereafter, the distribution of the cerebral blood flow developed to the cerebral cortices in a posteroanterior direction [22]. Other functional changes are also similar to these. Frontal lobes are the latest to mature in infancy in respect to the cerebral glucose metabolism [23,24]. The development on the EEG is also similar in that the development is from the occipital regions to the frontal regions [25]. The maturational changes of the cerebral cortices might proceed in the posteroanterior direction, except for the central regions. This circumscribed evidence supports the topographic specificity of temporo-occipital regions occurring in West syndrome, derived from this study. If a localized cerebral lesion will produce or facilitate infantile spasms, the region around the lesion must mature to a certain extent to provide neurons and neuronal connections with another
significant region for producing infantile spasms, such as a diencephalon and a brainstem in which the maturation precedes the cerebral cortices. In other words, West syndrome might occur when an irritative region in the cerebral cortex would be connected with the diencephalon and brainstem through an abnormal neuronal circuit in the critical developmental stage during infancy. Therapy for West syndrome, such as steroid therapy, could immediately inhibit the development of an abnormal neuronal circuit and cause the spasms to disappear. Maeda et al. [26,27] reported frequent involvement in the temporal or occipital regions (or both) by PET study in patients with idiopathic West syndrome. The hypometabolic lesions might include a lesion too small to detect by MRI. Otherwise, the transient hypometabolism in patients with good outcome would mean inhibition of the development of an abnormal circuit between irritable regions and brainstem to demonstrate a successful treatment. Furthermore, we should also recognize the region around the central sulcus as probably being a specific region, where maturation develops earlier than in the other frontal region in respect to myelination and cerebral blood flow [21,22]. The data in Tables 2 and 3 also suggest that the lesions on the right side correlate with West syndrome more closely than those on the left. The right predominance occurring West syndrome is probably caused by a developmental discrepancy between both cerebral hemispheres [28]. The developmental discrepancy is thought to be related to the sex of the patient [28]. However, our study did not reveal any sex difference in the occurrence of West syndrome because of the small number of patients. Additional studies involving a large number of patients are needed. The outcome of West syndrome with focal cortical lesions was reported to be usually unfavorable [3,20]. We hope that these investigations will be useful for the elucidation of the pathophysiology of West syndrome, from which adequate therapeutic options will be derived. We would like to thank Eric Johnson, Professor of Jichi Medical School, for editing our manuscript and Ms. N. Hadate for her useful support and persistent encouragement.
References [1] Yamamoto N, Watanabe K, Negoro T, et al. Partial seizures evolving to infantile spasms. Epilepsia 1988;29:34-40. [2] Carrazana EJ, Lombroso CT, Mikati M, Helmers S, Holmes GL. Facilitation of infantile spasms by partial seizures. Epilepsia 1993; 34:97-109. [3] Gastaut H, Gastaut JL, Re´gis H, et al. Computerized tomography in the study of West’s syndrome. Dev Med Child Neurol 1978;20:21-7. [4] Branch CE, Dyken PR. Choroid plexus papilloma and infantile spasms. Ann Neurol 1979;5:302-4. [5] Kurokawa T, Goya N, Fukuyama Y, Suzuki M, Seki T, Ohtahara S. West syndrome and Lennox-Gastaut syndrome: A survey of natural history. Pediatrics 1980;65:81-8. [6] Gabriel YH. Unilateral hemispheric ganglioglioma with infantile spasms. Ann Neurol 1980;7:287-8.
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[7] Sugiyama Y, Kajima T, Kamimura Y, et al. Intracranial cavernous hemangioma in the first decade of life (in Japanese). Nerv Syst Child 1981;6:107-16. [8] Mimaki T, Ono J, Yabuuchi H. Temporal lobe astrocytoma with infantile spasms. Ann Neurol 1983;14:695-6. [9] Hashimoto M, Tanaka T, Ohgami S, Yonemasu Y, Takahashi S. Intracerebral cavernous hemangioma in a child with Lennox-Gastaut syndrome transformed from West’s syndrome (in Japanese). Nerv Syst Child 1986;11:355-60. [10] Miyake S, Yamashita S, Yamada M, et al. Unilateral hemispheric neoplasm and infantile spasms (in Japanese). No To Hattatsu 1986;18:316-21. [11] Palm DG, Brandt M, Korinthenberg R. West syndrome and Lennox Gastaut syndrome in children with porencephalic cysts: Longterm follow-up after neurosurgical treatment. In: Niedermeyer E, Degen R, eds. The Lennox-Gastaut syndrome. New York: Alan R. Liss, 1988:419-26. [12] Ruggieri V, Caraball R, Fejerman N. Intracranial tumors and West syndrome. Pediatr Neurol 1989;5:327-9. [13] Shields WD, Chugani HT, Shewmon DA, Peacock W. Focal central nervous system lesions as a cause of infantile spasms. Cleve Clin J Med 1989;56:S-291. [14] Uthman BM, Reid SA, Wilder BJ, Andriola MR, Beydoun AA. Outcome for West syndrome following surgical treatment. Epilepsia 1991;32:668-71. [15] Asanuma H, Wakai S, Tanaka T, Chiba S. Brain tumors associated with infantile spasms. Pediatr Neurol 1995;12:361-4. [16] Chugani HT, Shewmon DA, Shields WD, et al. Surgery for intractable infantile spasms: Neuroimaging perspectives. Epilepsia 1993; 34:764-71. [17] Chugani HT, Shewmon DA, Sankar R, Chen BC, Phelps ME. Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography. Ann Neurol 1992;31:212-9.
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[18] Chugani HT, Da Silva E, Chugani DC. Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography. Ann Neurol 1996;39:643-9. [19] Plouin P, Dulac O, Jalin C, Chiron C. Twenty-four-hour ambulatory EEG monitoring in infantile spasms. Epilepsia 1993;34:68691. [20] Koo B, Hwang P. Localization of focal cortical lesions influences age of onset of infantile spasms. Epilepsia 1996;37:1068-71. [21] Kinney HC, Brody BA, Kloman AS, Gilles FH. Sequence of central nervous system myelination in human infancy. II. Patterns of myelination in autopsied infants. J Neuropathol Exp Neurol 1988;47: 217-34. [22] Kato T, Okuyama K. Assessment of maturation and impairment of the brain by I-123 iodoamphetamine SPECT and MR imaging in children. Showa Univ J Med Sci 1993;5:99-114. [23] Chugani HT, Phelps ME. Maturational changes in cerebral function in infants determined by 18FDG positron emission Tomography. Science 1986;231:840-3. [24] Chugani HT, Phelps ME, Mazziotta JC. Positron emission tomography study of human brain function development. Ann Neurol 1987;22:487-97. [25] Gasser T, Jennen-Steinmetz C, Sroka L, Verleger R, Mo¨cks J. Development of the EEG of school-age children and adolescents. II. Topography. Electroencephalogr Clin Neurophysiol 1988;69:100-9. [26] Maeda N, Watanabe K, Negoro T, et al. Transient focal cortical hypometabolism in idiopathic West syndrome. Pediatr Neurol 1993;9: 430-4. [27] Maeda N, Watanabe K, Negoro T, et al. Evolutional changes of cortical hypometabolism in West’s syndrome. Lancet 1994;343:1620-3. [28] de Lacoste M-C, Horvath DS, Woodward DJ. Possible sex differences in the developing human fetal brain. J Clin Exp Neuropsychol 1991;13:831-46.
Introduction In West syndrome, although classified as a generalized epilepsy, focal ictal features are not uncommon [1,2]. Some previously reported patients had West syndrome associated with distinct localized cerebral lesions in neuroradiologic studies [2-15]. Some of those patients became
From the *Division of Neurology; Saitama Children’s Medical Center; Saitama; and †Department of Pediatrics; Jikei University School of Medicine; Tokyo, Japan.
© 2000 by Elsevier Science Inc. All rights reserved. PII S0887-8994(00)00173-9 ● 0887-8994/00/$20.00
seizure free and had good developmental outcomes after resection of the localized lesions. Chugani et al. [16] reported that the patients with infantile spasms and normal magnetic resonance imaging (MRI) findings who underwent surgical resection of cerebral lesions with abnormal features on positron emission tomography (PET), exhibited good outcomes in seizure control and development. These investigators proposed the hypothesis of a corticalsubcortical interaction through the raphe nuclei as the pathophysiology of West syndrome as being more emphasized in the role of cortical lesions than previously postulated [16-18]. However, similar localized cortical abnormalities from the neonatal period usually can result in partial epilepsy instead of West syndrome. Additional factors to induce or facilitate West syndrome must exist, and those factors might include features of the cortical lesions, such as the pathologic findings, topographic localization, and side, and may be crucial in the pathophysiology of West syndrome. To determine whether the pathologic features, topographic localization, and side of the cerebral lesions are associated with West syndrome, we studied these features in relation to the seizure types and the findings of electroencephalography (EEG) in 39 epileptic patients with an isolated lesion, including five patients who presented with West syndrome. Material and Methods From all patients with epilepsy referred to the Saitama Children’s Medical Center between April 1983 and September 1998, we selected those satisfying the following criteria: an isolated lesion confined to a unilateral cerebral hemisphere and not extending over the whole hemisphere on MRI studies (1.5-T Siemens Magnetom), including T1weighted (TR-540-600 ms, TE-15 ms), T2-weighted (TR-300-3,500 ms, TE-90-93 ms), and proton density-weighted (TR-3,000-3500 ms, TE10-19 ms) images in the axial, coronal, and sagittal views, and duration of follow-up more than 3 years. We excluded patients with phacomatosis, mesial temporal sclerosis, an arachnoid cyst, a lesion presumed to be an
Communications should be addressed to: Dr. Hamano; Division of Neurology; Saitama Children’s Medical Center; 2100 Magome, Iwatsuki, Saitama 339-8551 Japan. Received January 10, 2000; accepted April 15, 2000.
Hamano et al: West Syndrome With Focal Lesions 219
Table 1.
Pt. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
Clinical characteristics of patients
Sex
Onset Age of Seizure
Age at Evaluation
Male Female Male Female Male Female Male Male Female Female Male Male Female Male Female Female Male Female Male Female Male Male Female Male Male Male Male Male Male Male Male Female Female Female Male Female Male Male Female
10 yr 6 mo 1 mo 8 yr 8 mo 7 mo 2 yr 2 mo 2 yr 6 mo 3 yr 9 mo 1 yr 3 mo 1 yr 3 mo 7 yr 3 mo 2 yr 6 mo 8 mo 5 yr 1 mo 5 yr 9 mo 8 yr 5 mo 4 yr 10 yr 7 mo 7 yr 5 mo 3 yr 9 mo 13 yr 10 mo 11 yr 2 yr 1 mo 10 yr 8 mo 11 yr 8 mo 1 yr 5 mo 14 yr 10 mo 3 yr 2 mo 1 yr 9 mo 3 yr 8 mo 2 yr 11 mo 2 yr 2 mo 4 mo 7 yr 8 mo 4 mo 7 mo 10 yr 5 mo 3 mo 5 mo
14 yr 3 mo 13 yr 6 mo 17 yr 6 mo 15 yr 8 yr 3 mo 5 yr 6 mo 10 yr 7 mo 9 yr 11 mo 6 yr 6 mo 20 yr 2 mo 7 yr 9 mo 3 yr 8 mo 9 yr 5 mo 12 yr 13 yr 7 mo 7 yr 21 yr 6 mo 12 yr 6 mo 14 yr 5 mo 21 yr 6 mo 16 yr 11 mo 12 yr 9 mo 21 yr 6 mo 20 yr 11 mo 14 yr 10 mo 10 yr 9 mo 19 yr 5 mo 13 yr 8 mo 10 yr 6 mo 7 yr 7 mo 6 yr 9 mo 5 yr 9 mo 9 yr 6 mo 19 yr 9 mo 4 yr 3 mo 6 yr 11 mo 13 yr 8 mo 5 yr 11 mo 21 yr 1 mo
Abbreviations: aT ⫽ Anteriotemporal C ⫽ Central F ⫽ Frontal Fp ⫽ Frontpolar L ⫽ Left mT ⫽ Midtemporal
Lesions Type on MRI Studies Tumorous lesion Tumorous lesion Cortical heterotopia Focal atrophy Spot lesion in white Focal atrophy Spot lesion in white Tumorous lesion Tumorous lesion Tumorous lesion Cortical dysplasia Spot lesion in white Tumorous lesion Focal atrophy Focal atrophy Porencephary Spot lesion in white Focal atrophy Spot lesion in white Focal atrophy Focal atrophy Spot lesion in white Porencephary Porencephary Tumorous lesion Tumorous lesion Tumorous lesion Focal atrophy Focal atrophy Focal atrophy Cortical dysplasia Porencephary Focal atrophy Focal atrophy Cortical heterotopia Porencephary Focal atrophy Cortical dysplasia Porencephary
matter
⫹(L-FFp) ⫹(L-F) ⫹(L-F) ⫹(L-F) ⫹(R-F) ⫹(L-C) ⫹(L-F) ⫹(R-FC)
⫹(L-O) ⫹(L-O)
⫹(R-CF)
⫹(R-O)
⫹(R-F,O) ⫹(R-F) ⫹(R-F,O)
⫹(L-FFp) ⫹(L-FC)
matter
matter
⫹(R-F) ⫹(R-F) ⫹(R-FCP) ⫹(L-PO) ⫹(G) ⫹(R-PC)
matter
matter
⫹(R-F) ⫹(R-mTP) ⫹(L-aT) ⫹(R-aT) ⫹(L-mT) ⫹(L-aTmT) ⫹(R-pTP) ⫹(R-OpT) ⫹(R-O) ⫹(L-OpT) ⫹(R-O) ⫹(L-O) ⫹(R-O)
⫹(L-F) ⫹(L-F) ⫹(R-F,O) ⫹(R-F,O)
⫹(L-PC)
⫹(R-F,O) ⫹(R-aT)
⫹(L-F,O) ⫹(L-F,P)
⫹(R-FFp) ⫹(R-F) ⫹(L-O,Fp) ⫹(R-F) ⫹(L-FC) ⫹(L-FCP) ⫹(R-FFp) ⫹(R-CP) ⫹(L-FCP) ⫹(R-CP) ⫹(L-F)
⫹(R-mT,F)
⫹(L-O) ⫹(L-OP,F) ⫹(R-O,F) ⫹(L-FFP,O)
O ⫽ Occipital P ⫽ Parietal Pt. No. ⫽ Patient number pT ⫽ Posteriotemporal R ⫽ Right
insult after a perinatal period, or a lesion exhibiting progressive changes on MRI during a follow-up period. The medical records of these patients were reviewed for the age at onset of epilepsy, seizure types, interictal EEG recordings, including, if applicable, ictal recordings, neurologic status, and long-term outcome of epilepsy. Thirty-nine patients met these criteria. The patients (23 males and 16 females) ranged in age from 3 years, 8 months to 21 years, 6 months (mean ⫽ 12 years, 6 months) at the time of the evaluation. The follow-up periods ranged from 3 to 13.4 years (mean ⫽ 6.9).
Results The average age at the onset of epilepsy was 4 years, 9 months (range ⫽ 1 month to 14 years, 10 months).
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Complications included mental retardation in 18 patients, hemiplegia in 11 patients, behavioral disorders in one patient, and tics in one patient (Table 1). MRI findings conformed to six categories: focal atrophy in 13 patients; a tumorous lesion in nine patients; porencephaly in six patients; a spot lesion in the white matter that was a small oval lesion with low intensity on T1-weighted and high intensity on T2-weighted images and probably indicated gliosis in the white matter in six patients; cortical dysplasia in three patients, and cortical heterotopia in two patients. Of these patients, Patient 38 underwent lesionectomy, and the lesion was pathologically diagnosed as focal
cortical dysplasia. The other patients had not been treated surgically. The presumed diagnosis of patients having a tumorous lesion, on the basis of MRI and computed tomography, was as follows: astrocytoma in Patients 1, 8, 9, 13, and 27; ganglioglioma in Patients 25 and 26; cavernous hemangioma in Patient 2; and dysembryoplastic neuroepithelial tumor in Patient 10. All patients presented with a partial seizure; 15 patients also had secondarily generalized seizures (Table 1 and Table 2). Epileptic spasms preceded or followed partial seizures in five patients (Patients 24, 33, 35, 38, and 39) manifesting hypsarrhythmia who were diagnosed with West syndrome; three of them were male. In Patient 38, ocular deviation to the left proceeded to epileptic spasms, and the seizures were intractable to antiepileptic drugs and adrenocorticotropin. His development was severely retarded, and he could neither sit alone nor speak a word at 4 years of age. After the lesionectomy at 4 years, 7 months of age, his development improved slightly, and seizures were not observed for 9 months. His seizures recurred daily from 5 years, 4 months of age. The partial seizures of the other patients with West syndrome followed epileptic spasms, which disappeared after administration of adrenocorticotropin or antiepileptic drugs. The partial seizures of the four patients with West syndrome occurred at the age of 13 years, 5 months in Patient 24, 1 year, 1 month in Patient 33, 2 years, 10 months in Patient 35, and 8 years, 11 months Patient 39. The partial seizures of Patients 24 and 39 had been controlled through antiepileptic drugs for the previous 2 years. The partial seizures of Patient 33 occurred monthly; those of patients 35 and 38 occurred daily. Ictal EEGs recorded in Patients 3 and 38 revealed that the initial discharge on the onset of partial seizures corresponded with the lesions detected on MRI. In the 27 patients, including Patients 3 and 38, the interictal discharges corresponded to the lesions. Five patients had no paroxysmal discharge on the interictal EEG recording through the follow-up period. Paroxysmal discharges in the other ipsilateral regions were less often observed in the patients with a frontal lesion; they were more common in the patients with a lesion in other regions. Contralateral paroxysmal discharges to the lesions were observed in 15 patients independently of the localization of the lesions. Table 2 presents the topographic localization of the lesions of the 39 patients. Of all 39 patients, 16 patients had lesions in the frontal lobe, 11 patients had lesions in the parietal lobe, 19 patients had lesions in the temporal lobe, and nine patients had lesions in the occipital lobe. The lesions of all five patients with West syndrome were in the temporal or occipital lobes (or both). Among the nine patients with a lesion in the occipital lobe, four patients were diagnosed with West syndrome. In the 19 patients with a lesion in the temporal lobe, three patients had West syndrome. However, in the 15 patients with a lesion in the frontal or parietal lobes (or both) without involvement of the temporal and occipital lobes, none
Table 2.
Topography of lesions and type of seizures
, partial seizures only. , partial seizures and secondarily generalized seizures. , epileptic spasms with or without partial seizures.
exhibited epileptic spasms. The side of the brain with the lesion was the right in the four patients with West syndrome; 23 patients had the lesion on the right side and 16 patients on the left side. Discussion Although this is a relatively small series of 39 epileptic patients with a varied localized cerebral lesion, some particular features are apparent. West syndrome was more common in the patients with a temporo-occipital lesion than in those with a frontal lesion and occurred more often in patients with lesions localized on the right than the left hemisphere. West syndrome associated with a defined localized lesion such as a tumor or porencephaly, has been
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Table 3.
Topography of lesions of West syndrome with localized lesions previously reported
previously reported. Table 3 presents the topographic localization and diagnosis of the lesion of the patients with West syndrome who had been previously reported [2-12, 14,15]. In 17 patients, five had a lesion without obvious involvement of the cerebral cortex. The lesions involved
the basal ganglia, lateral ventricle, optic nerve, thalamus, and hypothalamus [3-5,12,15]. The data in Table 3 revealed that temporal involvement was common in West syndrome associated with localized cerebral lesions and that lesions were more often on the right than the left
Table 4. Topography of lesions on positron emission tomography study of West syndrome by Chugani et al. [16]
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hemisphere. Chugani et al. [16] reported 23 patients with intractable infantile spasms, including 13 patients with normal MRI findings, who had a good outcome after resection of the lesions. The patients were evaluated by PET studies. The lesions in seven patients extended to the whole cerebral hemisphere or were bilateral. Among the other 16 patients, only two patients had frontal lesions. However, 15 of the 16 patients had lesions that involved a temporal lobe, 13 patients had involvement in an occipital lobe, and 14 patients exhibited an abnormality in a parietal lobe on PET studies (Table 4). Although the difference in the side was not significant, temporo-occipital involvement was common in the study by Chugani et al. [16]. All but three patients had a good outcome after resection of these lesions, as evaluated by PET, and the resected lesions exhibited pathologic abnormalities [16]. It is likely that the lesions revealed by PET were not transient abnormalities and that they were the crucial lesions in terms of the epileptic spasms, irrespective of the normal MRI findings. The study of 24-hour ambulatory EEG monitoring in infantile spasms accompanied with partial seizures revealed that partial seizures originated from the temporal and rolandic regions and originated more often from the right hemisphere in most cases [19]. Koo and Hwang [20] studied the onset age of infantile spasms in 93 patients with focal cerebral findings, including functional lesions detected by PET, single positron emission tomography, and EEG. Their conclusions were that occipital lesions were associated with the earliest age of onset of spasms, and that frontal lesions were rare and associated with the latest onset of spasms. These results are substantially consistent with our results. West syndrome is an age-dependent epilepsy occurring in infancy. The high incidence of West syndrome with partial seizures that originate from a (centro-)temporooccipital region could be a result of normal brain maturation. Myelination in normal brain develops from the central regions toward each pole of the cerebral lobes, and occipital poles myelinate before the fronto-temporal poles [21]. Kato and Okuyama [22] reported that the distribution of cerebral blood flow began from the cerebellums, thalamus, basal ganglia, and central regions. Thereafter, the distribution of the cerebral blood flow developed to the cerebral cortices in a posteroanterior direction [22]. Other functional changes are also similar to these. Frontal lobes are the latest to mature in infancy in respect to the cerebral glucose metabolism [23,24]. The development on the EEG is also similar in that the development is from the occipital regions to the frontal regions [25]. The maturational changes of the cerebral cortices might proceed in the posteroanterior direction, except for the central regions. This circumscribed evidence supports the topographic specificity of temporo-occipital regions occurring in West syndrome, derived from this study. If a localized cerebral lesion will produce or facilitate infantile spasms, the region around the lesion must mature to a certain extent to provide neurons and neuronal connections with another
significant region for producing infantile spasms, such as a diencephalon and a brainstem in which the maturation precedes the cerebral cortices. In other words, West syndrome might occur when an irritative region in the cerebral cortex would be connected with the diencephalon and brainstem through an abnormal neuronal circuit in the critical developmental stage during infancy. Therapy for West syndrome, such as steroid therapy, could immediately inhibit the development of an abnormal neuronal circuit and cause the spasms to disappear. Maeda et al. [26,27] reported frequent involvement in the temporal or occipital regions (or both) by PET study in patients with idiopathic West syndrome. The hypometabolic lesions might include a lesion too small to detect by MRI. Otherwise, the transient hypometabolism in patients with good outcome would mean inhibition of the development of an abnormal circuit between irritable regions and brainstem to demonstrate a successful treatment. Furthermore, we should also recognize the region around the central sulcus as probably being a specific region, where maturation develops earlier than in the other frontal region in respect to myelination and cerebral blood flow [21,22]. The data in Tables 2 and 3 also suggest that the lesions on the right side correlate with West syndrome more closely than those on the left. The right predominance occurring West syndrome is probably caused by a developmental discrepancy between both cerebral hemispheres [28]. The developmental discrepancy is thought to be related to the sex of the patient [28]. However, our study did not reveal any sex difference in the occurrence of West syndrome because of the small number of patients. Additional studies involving a large number of patients are needed. The outcome of West syndrome with focal cortical lesions was reported to be usually unfavorable [3,20]. We hope that these investigations will be useful for the elucidation of the pathophysiology of West syndrome, from which adequate therapeutic options will be derived. We would like to thank Eric Johnson, Professor of Jichi Medical School, for editing our manuscript and Ms. N. Hadate for her useful support and persistent encouragement.
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