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Generalized spike-and-wave patterns in children: clinical correlates
Generalized Spike-and-Wave Patterns in Children: Clinical Correlates Beatriz Martı´nez-Mene´ndez, MD, PhD*, Angel Pe´rez Sempere, MD, PhD†, Pilar de la Pen˜a Mayor, MD‡, Rogelio Simo´n de las Heras, MD§, ´ lvarez-Tejerina, MD‡, and Fernando Mateos-Beato, MD, PhD§ Julian A All electroencephalograms performed in our institution between 1980 and 1990 were reviewed. The clinical characteristics of children with epilepsy and generalized spike-and-wave (SW) patterns were analyzed. The SW patterns were classified according to their frequency. Electroencephalograms of 154 children with epilepsy revealed SW patterns. Absence seizures were the most common first seizure, but partial seizures were frequent. More than 40% had several types of seizures. Sixty percent of the epileptic syndromes were generalized, but almost 25% were partial. The typical SW pattern was associated with absence seizures, a normal examination and computed tomographic scan, idiopathic generalized epilepsies, monotherapy, freedom from seizures, and lack of recurrence. The slow SW pattern was associated with West syndrome; a younger age at seizure onset; atonic, myoclonic, tonic, and partial simple seizures; an abnormal examination and computed tomographic scan; cryptogenic or symptomatic generalized epilepsy or symptomatic partial epilepsy; polytherapy; and poor seizure control. The fast SW pattern was associated with secondary generalized, partial, tonic-clonic, and complex partial seizures; a normal computed tomographic scan; cryptogenic partial epilepsy; isolated seizures; and seizure recurrence. Epilepsy with a typical SW pattern should be considered benign, epilepsy with a slow SW pattern malignant, and epilepsy with a fast SW pattern treacherous. © 2000 by Elsevier Science Inc. All rights reserved. Martı´nez-Mene´ndez B, Pe´rez Sempere A, de la Pen˜a ´ lvarez-Tejerina J, Mayor P, Simo´n de las Heras R, A Mateos-Beato F. Generalized spike-and-wave patterns in children: Clinical correlates. Pediatr Neurol 2000;22: 23-28.
From the *Pediatric Neurology Unit; Section of Neurology; H.U. de Getafe; †Neurology Unit; Hospital de la Vega Baja; Orihuela, Alicante; ‡Electroencephalography Unit; Section of Neurology; § Pediatric Neurology Unit; Section of Neurology; Hospital 12 de Octubre; Madrid, Spain.
© 2000 by Elsevier Science Inc. All rights reserved. PII S0887-8994(99)00115-0 ● 0887-8994/00/$20.00
Introduction The classification of epileptic seizures is useful in the diagnosis and treatment of patients with epilepsy [1]. However, the seizure type provides only limited information about the prognosis and therapeutic decisions. The International Classification of the Epilepsies and the Epileptic Syndromes [2] considers not only the semiology of the seizures but also other factors, such as the age of onset and the possible etiology. This classification is useful in epileptology, especially for pediatric patients [3]. The generalized spike-and-wave (SW) patterns were first described in a patient with absence seizures [4]. The SW patterns have been differentiated on the basis of their frequency [5-9], and they have been evaluated according to the different pathologic situations associated with them. However, this study is the first to analyze the clinical characteristics of children with epilepsy and the electrical-clinical correlation of the different electroencephalographic patterns in childhood using the international classifications. Subjects and Methods The authors reviewed all of the electroencephalograms (EEGs) (n ⫽ 39,322) performed between January 1980 and December 1990 in the EEG unit of Hospital 12 de Octubre, Madrid, Spain. This hospital serves a population of about 650,000 and was the only center in this area where the technique could be utilized. The SW pattern was observed in 1,068 EEGs from 654 patients, 213 of whom (33%) were younger than 14 years of age. Adequate information was available for only 170 patients, 16 of whom did not have epilepsy and were not included in the present study. The patients who had experienced only febrile seizures were not considered to have epilepsy. The mean follow-up time for the included patients was 4.5 years (S.D. ⫽ 2.86). The patient’s files were reviewed by the same pediatric neurologist, and all relevant information regarding personal and family history, clinical characteristics, and electroencephalographic data was analyzed.
Communications should be addressed to: Dr. Martı´nez-Mene´ndez; U. Neuropediatrı´a; S. Neurologı´a; H.U. Getafe; Ctra de Toledo Km 12,400; 28905-Gefate; Madrid, Spain. Received February 12, 1999; accepted August 26, 1999.
Martı´nez-Mene´ndez et al: Clinical Correlates of Spike-and-Wave Patterns 23
Table 1.
Table 2.
Patients’ histories
Pathologic pregnancy Pathologic delivery Asphyxia Pathologic neonatal period Neonatal seizures Abnormal psychomotor development West syndrome Febrile seizures Head trauma Central nervous system infection Learning difficulties
Common associations of seizures
n
%
Association
n
%
4 16 12 6 3 16 6 22 2 2 28*
2.6 10.4 7.8 3.9 1.95 10.4 3.9 14.3 1.3 1.3 18.2
Absence ⫹ T-C Myoclonic ⫹ T-C SP ⫹ T-C Myoclonic ⫹ Absence CP ⫹ T-C CP ⫹ SP SP ⫹ Sec. generalized
27 22 19 17 8 8 6
17.6 17.5 12.4 11.1 5.2 5.2 3.9
Abbreviations: CP ⫽ Complex partial Sec. ⫽ Secondary
SP ⫽ Simple partial T-C ⫽ Tonic-clonic
* Two of these children presented with progressive mental deterioration.
The 39,322 EEGs had all been recorded with the ALVAR (Paris, France), model XVI TR, with 16 channels, using the 10-20 International System [10], with bipolar and referential montages. All EEGs were reviewed by the same electroencephalographers. The EEG study included background, focal paroxysmal discharges, generalized paroxysmal discharges, with or without focal onset, asymmetric discharges, and association of focal and generalized epileptiform abnormalities. A SW was defined as a generalized paroxysmal discharge, clearly distinguished from background, consisting of a spike followed by a wave [11]. The SWs were classified according to their frequencies into three groups: typical, three cycles per second; slow, less than three cycles per second; and fast, more than three cycles per second. Continuous variables were compared using Student’s unpaired t test. Discrete variables were compared using the chi-square test and odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at P ⬍ 0.05. All probabilities are two-tailed values.
Results The EEGs of 154 children with epilepsy revealed SW patterns. The mean age at seizure onset was 6 years, 6 months (S.D. 3.7; range ⫽ 0-14 years). The mean age at the first EEG was 7 years, 6 months (S.D. 3.6; range ⫽ 0.83-14 years). The sex distribution was about 1:1 (53% females and 47% males). The patients’ medical histories are recorded in Table 1. Eighteen percent of the children had learning difficulties at school, and 14% also had febrile seizures. The family history of epilepsy and febrile seizures was investigated among first-degree
Figure 1. Distribution of frequencies according to the type of first and total seizures. Sec.: secondary.
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and second-degree relatives; 10% of first-degree relatives had epilepsy. The most frequent type of seizure at presentation for the first seizure was absence seizures (35.5%), followed by tonic-clonic seizures (27%), complex partial seizures (14%), secondary generalized seizures (8%), and simple partial seizures (6%) (Fig 1). Two patients (1.31%) presented with complex partial status epilepticus. Only 33 of the patients (21.4%) consulted with physicians after their first seizure; 59% of them had experienced tonic-clonic seizures, 21.9% complex partial seizures, 18.7% secondary generalized seizures, and 3.1% simple partial seizures. Of the 121 children (78.6%) who consulted with physicians after their second seizure, 11 (9.1%) requested medical consultation after a tonic-clonic seizure or an episode of status epilepticus, although they had previously had absence or partial seizures. More than 40% of the patients had several types of seizures. The global distribution of seizures (Fig 1) was different than the distribution of the first seizures. The most common type was tonic-clonic seizures (48%), followed by absence seizures (46%), complex partial seizures (20.5%), myoclonic seizures (18%), and simple partial seizures (18%). Thirteen children (8.4%) had status epilepticus of one type or another at some time during their illness. The most common associations of seizures were absence seizures or myoclonic seizures with tonicclonic seizures (Table 2). The classification of the patients according to the
⫽ 2.98) or fast SW patterns (mean ⫽ 7 years, S.D. ⫽ 3.9) (P ⬍ 0.001). The typical SW pattern was associated with learning difficulties less frequently than the other SW patterns (OR ⫽ 0.33; 95% CI ⫽ 0.12-0.92%). The typical SW pattern was usually associated with only one type of seizure (OR ⫽ 3.3; 95% CI ⫽ 1.57-6.92%), especially absence seizures (OR ⫽ 13.7) (Tables 3 and 4). The neurologic examination was usually normal (OR ⫽ 4.25; 95% CI ⫽ 1.65-12.3%) as was the cranial computed tomography (CT) scan (OR ⫽ 15.6; 95% CI ⫽ 1.48101%). The typical SW pattern was mainly associated with the idiopathic generalized epilepsies (OR ⫽ 9.24) and had the best outcome (Tables 3 and 4). The slow SW pattern was associated with West syndrome (OR ⫽ 37.1; 95% CI ⫽ 4.11-335%), pathologic pregnancy (OR ⫽ 7.69; 95% CI ⫽ 1.43-50%), abnormal psychomotor development (OR ⫽ 7.14; 95% CI ⫽ 2.520%), learning difficulties (OR ⫽ 6.1; 95% CI ⫽ 2.3515.7%), and the presence of more than one seizure type (OR ⫽ 5.25; 95% CI ⫽ 1.96-14.28%), especially atonic, myoclonic, tonic, and partial seizures (Tables 3 and 4). The neurologic examination and cranial CT scan were abnormal more frequently (OR ⫽ 7.69; 95% CI ⫽ 3.13-20% and OR ⫽ 54; 95% CI ⫽ 6.25-500%, respectively) than with other SW patterns. The slow SW pattern was primarily associated with symptomatic partial epilepsies (OR ⫽ 25.2), cryptogenic or symptomatic generalized
Figure 2. Distribution of frequencies according to epileptic syndromes. Sec: secondary. Special S.: special syndrome; PGE: uncertain epilepsies between partial or generalized; SGE: symptomatic generalized epilepsies; CSGE: cryptogenic or symptomatic generalized epilepsies; IGE: idiopathic generalized epilepsies; CPE: cryptogenic partial epilepsies; SPE: symptomatic partial epilepsies; IPE: idiopathic partial epilepsies.
International Classification of Epileptic Syndromes (Fig 2) was as follows: idiopathic generalized epilepsy (49%), cryptogenic partial epilepsy (13%), idiopathic partial epilepsy (8%), undetermined whether partial or generalized (8%), cryptogenic or symptomatic generalized (8%), special syndromes (8%), symptomatic partial epilepsy (3%), and symptomatic generalized epilepsy (3%). Children with slow SW patterns were younger at the onset of seizures (mean ⫽ 3.7 years, S.D. ⫽ 3.17) than children with typical SW patterns (mean ⫽ 7.1 years, S.D.
Table 3.
Seizure types, epileptic syndromes, and outcomes according to SW pattern correlation
Seizure types Absence Tonic-clonic Tonic Myoclonic Atonic Simple partial Complex partial Secondary generalized Epileptic syndromes IPE SPE CPE IGE CSGE SGE PGE Special syndromes Outcomes Seizure free Recurrence
OR
Typical SW 95% CI
OR
95% CI
OR
95% CI
13.7 0.16 0.34 0.19 0.05 0.27 0.27 0.27
5.99-31.3 0.08-0.35 0.04-2.99 0.05-0.65 0.01-0.77 0.09-0.83 0.1-0.76 0.08-0.97
0.68 1.64 5.95 6.37 26.2 4.2 1.03 0.93
0.28-1.67 0.68-3.96 1.13-31.5 2.42-16.8 7.3-94.3 1.58-11.2 0.35-3.03 0.25-3.47
0.12 3.68 0.53 0.91 0.36 0.99 2.8 5.77
0.06-0.25 1.88-7.21 0.94-2.97 0.39-2.13 0.11-1.18 0.42-2.36 1.21-6.42 1.58-21
0.558 0.274 0.164 9.24 0.061 1.43 0.863 0.325
0.14-2.15 0.03-2.33 0.04-0.73 4.19-20.4 0.01-0.92 0.37-5.55 0.25-3.01 0.07-1.53
0.46 25.2 0.206 0.228 24.8 3.76 1.87 0.357
0.06-3.73 2.68-237 0.03-1.6 0.08-0.65 6.04-102 0.59-23.8 0.47-7.49 0.045-2.86
2.34 0.264 12.8 0.306 0.338 1.67 1.89 6.21
0.67-8.15 0.03-2.42 2.88-57.6 0.157-0.6 0.09-1.3 0.27-10.3 0.43-8.21 1.31-29.4
9.15 0.151
2-41 0.29-0.77
0.15 0.3
0.05-0.42 0.04-2.74
Abbreviations: CI ⫽ Confidence interval CPE ⫽ Cryptogenic partial epilepsies CSGE ⫽ Cryptogenic or symptomatic generalized epilepsies IGE ⫽ Idiopathic generalized epilepsies IPE ⫽ Idiopathic partial epilepsies
Slow SW
OR PGE SGE SPE SW
⫽ ⫽ ⫽ ⫽ ⫽
Fast SW
0.9 11.8
0.4-2.05 2.32-61
Odds ratio Uncertain epilepsies between partial and generalized Symptomatic generalized epilepsies Symptomatic partial epilepsies Spike-and-wave
Martı´nez-Mene´ndez et al: Clinical Correlates of Spike-and-Wave Patterns 25
Table 4.
Variables associated with the typical, slow, and fast SW
Typical SW Absence of learning difficulties Single type of seizure Absence seizures (inversely associated with the rest of seizure types) Normal neurologic examination Normal cranial CT scan Idiopathic generalized epilepsy Control of seizures with monotherapy Seizure free Absence of recurrence after drug withdrawal Slow SW Pathologic pregnancy Psychomotor developmental abnormalities Learning difficulties West syndrome More than one type of seizure Younger age at seizure onset Atonic, myoclonic, tonic, and partial simple seizures Normal neurologic examinaton Abnormal cranial CT scan Cryptogenic or symptomatic generalized epilepsy or symptomatic partial epilepsy Polytherapy Poor control of seizures Absence of recurrence after drug withdrawal Fast SW Partial seizures with secondary generalization, tonic-clonic, and partial complex seizures Normal cranial CT scan Cryptogenic partial epilepsies or isolated seizures Recurrence of seizures after drug withdrawal Abbreviations: CT ⫽ Computed tomography SW ⫽ Spike-and-wave
epilepsy (OR ⫽ 24.8) (Tables 3 and 4), and poor seizure control (Tables 3 and 4). The fast SW pattern was associated with tonic-clonic, partial complex, and secondary generalized seizures but was infrequently associated with absence seizures (Tables 3 and 4). The fast SW pattern was also associated with normal cranial CT (OR ⫽ 3.55; 95% CI ⫽ 1.14-11.11%) and cryptogenic partial epilepsy (OR ⫽ 12.8) (Tables 3 and 4). Patients with a fast SW pattern had the highest risk of recurrence (Tables 3 and 4). It was not possible to demonstrate an association between the different discharge types and some of the studied variables (sex, childbirth type, asphyxia, pathologic neonatal period, neonatal seizures, febrile seizures, head trauma, infections of the central nervous system, family history of epilepsy, family history of febrile seizures, and other EEG variables). Discussion The present study covers the entire pediatric age group. The age distribution at the onset of seizures demonstrated a higher rate of onset in the first year, a smaller rate of onset in the second year, and similar rates in the following years. Other investigators obtained a similar age distribu-
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tion among patients with epilepsy in general [12-16]. The rate of epilepsy onset is considered to be highest in the first year after birth and gradually declines after 10 years of age [16,17]. In this study the incidence of epilepsy in the children with SW patterns declined after 8 years of age. We intuitively linked SW patterns to absence seizures. In fact, this seizure type was the most frequent one of the first seizures in this study (36%), but tonic-clonic seizures were more common in the whole series (44%), and even partial seizures accounted for 37% of seizures. A great number of children had several types of seizures. The most frequent associations were absence and tonic-clonic seizures and myoclonic and tonic-clonic seizures. Nineteen percent of the patients with SW patterns had only partial seizures. It is difficult to compare the results of this study with previous ones because of methodologic problems. In general terms, all the seizure types had a higher frequency in the classic works [18,19]. However, in the study of Silverman, [18] partial seizures were almost nonexistent, and in the study of Lunndervold et al. [19] the frequency of partial seizures was important. Gastaut [8] in his study of generalized SW bursts did not even mention partial seizures. When the distribution of the frequencies of the different epileptic syndromes was analyzed [2], 60% of them were classified as generalized and nearly 50% were considered idiopathic, but almost 25% were partial epileptic syndromes. It was difficult to differentiate between partial and generalized in 8% of the patients, and the remaining 8% were special syndromes. The authors could not compare these results with other studies because, to their knowledge, no equivalent study has been published. Among patients with epilepsy in general, however, partial epilepsies predominate, and a great variability exists with regard to the uncertain epileptic syndromes and special syndromes [17,20-25]. The correlation of the three different types of SW patterns with the clinical characteristics and outcome of the patients is not well established. According to Gastaut [8] the presence of a family history of epilepsy was frequent in patients with typical SW patterns, relatively frequent in persons with fast SW patterns, and uncommon in patients with slow SW patterns. However, the authors could not demonstrate any association between the type of SW pattern and variables, such as sex, childbirth type, asphyxia, febrile seizures, neonatal seizures, head trauma, or central nervous system infections; all were associated in the classic studies with the slow SW pattern [8,19]. No series of patients with different SW types has been published to date. For this reason, we could only compare data with infantile absence seizures or the Lennox-Gastaut syndrome. Standard textbooks state that absence seizures are more frequent in girls, that a family history of epilepsy is common, and that the patient’s personal medical history is irrelevant. On the other hand the Lennox-Gastaut syndrome is more frequent in males without a family history of epilepsy, and frequently the investigators discovered significant medical diseases in the patient’s med-
ical history [26-28]. However, as stated previously, we did not encounter these associations with the typical SW and slow SW patterns. In the present study the only variables that were associated with a SW pattern were pathologic pregnancy (eight times more common in the children with a slow SW pattern), retarded psychomotor development (eight times more common in the patients with a slow SW pattern), personal history of West syndrome (37 times more frequent in the children with a slow SW pattern), and learning difficulties. The slow SW pattern has generally been related to the Lennox-Gastaut syndrome [28-31]. The association of the slow SW pattern with West syndrome is also well known, although it had not been previously quantified. Learning difficulties are associated with the slow SW pattern in the same way as they are with the Lennox-Gastaut syndrome [6,7,30-33], in which intellectual deficits appear in a high percentage of patients. When the age at which the first seizures occurred was analyzed, we observed that seizures began at a younger age in children with a slow SW pattern than in children with typical or fast SW patterns. The slow SW pattern was also associated with a child having more than one seizure type (OR ⫽ 5) and with atonic seizures (OR ⫽ 26), myoclonic seizures (OR ⫽ 6), tonic seizures (OR ⫽ 6), and simple partial seizures (OR ⫽ 4). The authors documented a strong correlation between the slow SW pattern and cryptogenic or symptomatic generalized epilepsy (OR ⫽ 25), which demonstrates the association of this EEG pattern with the Lennox-Gastaut syndrome and confirms the findings of the classic works [6,33] by statistical methods. This correlation was not unique because the slow SW pattern also had a similar association with symptomatic partial epilepsies. As is widely known, absence seizures are associated with the typical SW pattern. The authors determined a strong correlation between the typical SW pattern and the presence of absence seizures (OR ⫽ 13.7) and idiopathic generalized epilepsies (OR ⫽ 9.2). The results of cranial CT paralleled those of the neurologic examination (i.e., normal results in the typical and fast SW patterns and abnormal in the slow SW pattern). The data regarding the fast SW pattern may be more interesting because they are less well known. The fast SW pattern was associated with secondary generalized partial seizures (OR ⫽ 6), tonic-clonic seizures (OR ⫽ 4), and partial complex seizures (OR ⫽ 3). Cranial CT was usually normal. The fast SW pattern was also associated with the cryptogenic partial epilepsies and the isolated seizures and was inversely associated with the idiopathic generalized epilepsies. We observed an association between slow and fast SW patterns and partial epilepsy. The slow SW pattern was not only associated with cryptogenic or symptomatic generalized epilepsy but also with symptomatic partial epilepsy. This association of SW patterns and partial epilepsies is especially intense in the case of the fast SW pattern, in
which the association is only demonstrated with partial epilepsies and isolated seizures. That children with a typical SW pattern were almost 10 times as likely to be seizure free and had few recurrences (OR ⫽ 0.15) than those children with atypical SW patterns may indicate that it is a more benevolent illness. In this study the possibility of children with a slow SW pattern to be free of seizures was scarce (OR ⫽ 0.15). However, if they were able to be without medication the possibility that their illness would not recur was higher. Children with a fast SW pattern had a higher risk of recurrence (OR ⫽ 12). In conclusion, although generalized epilepsies predominate among children with epilepsy associated with SW patterns, a significant number of these patients suffer from partial epilepsies. The epilepsy of children with a typical SW pattern can be considered benign in contrast to the epilepsy of children with a slow SW pattern, which can be considered malignant. The epilepsy course of children with a fast SW pattern can be difficult to predict because the pattern was associated with either isolated seizures or seizure recurrence.
References [1] International League Against Epilepsy. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501. [2] International League Against Epilepsy. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for Classification of Epilepsies and Epileptic Syndromes. Epilepsia 1989;30:389-99. [3] Dulac O. Epileptic syndromes in infancy and childhood: Recent advances. Epilepsia 1995;36 (Suppl 1):S51-7. [4] Gibbs FA, Davis H, Lennox WG. The electroencephalogram in epilepsy and in conditions of impaired consciousness. Arch Neurol Psychiatry (Chicago) 1935;34:1133-48. [5] Gibbs FA, Gibbs EL, Lennox WG. The influence of blood sugar level on the wave and spike formation in petit mal epilepsy. Arch Neurol Psychiatry (Chicago). 1939;47:1111-6. [6] Lennox WG, Davis JP. Clinical correlates of the fast and the slow spike-wave electroencephalogram. Pediatrics 1950;5:626-44. [7] Gastaut H, Roger J, Soulayrol R, et al. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia 1966;7:139-79. [8] Gastaut H. Clinical and electroencephalographic correlates of generalized spike and wave bursts occurring spontaneously in man. Epilepsia 1968;9:179-84. [9] Niedermeyer E. The Lennox-Gastaut syndrome: A severe type of childhood epilepsy. D Z Nervenheilk 1969;195:263-83. [10] Jasper HH. The ten-twenty electrode system of the International Federation. Electroencephalogr Clin Neurophysiol 1958;10:371-3. [11] Chatrian GF, Bergamini Y, Dondey M, Klass EW, LennoxBuchtal M, Peterse´n Y. A glossary of terms most commonly used by clinical electroencephalographers. Electroencephalogr Clin Neurophysiol 1974;37:538-48. [12] Annegers JF. The epidemiology of epilepsy. In: Wyllie E, ed. The treatment of epilepsy: Principles and practices. Philadelphia: Lea & Febiger, 1993;157-64. [13] Nieto M, Pita E. Aspectos epidemiolo´gicos. In: Nieto M, ed. Epilepsias y sı´ndromes epile´pticos en el nin˜o. Granada: Universidad de Granada, 1993;37-46.
Martı´nez-Mene´ndez et al: Clinical Correlates of Spike-and-Wave Patterns 27
[14] Hauser WA. The prevalence and incidence of convulsive disorders in children. Epilepsia 1994;35 (Suppl 2):S1-6. [15] Murphy CC, Trevathan E, Yeargin-Allsopp M. Prevalence of epilepsy and epileptic seizures in 10 year old children: Results from the Metropolitan Atlanta Developmental Disability Study. Epilepsia 1995; 36:866-72. [16] Camfield CS, Camfield PR, Gordon K, Wirell E, Dooley JM. Incidence of epilepsy in childhood and adolescence: A population-based study in Nova Scotia from 1977 to 1985. Epilepsia 1996;37:19-23. [17] Eriksson KJ, Koivikko MJ. Prevalence, classification, and severity of epilepsy and epileptic syndromes in children. Epilepsia 1997;38:1275-82. [18] Silverman D. Clinical correlates of the spike-wave complex. Electroencephalogr Clin Neurophysiol 1954;6:663-9. [19] Lundervold A, Henriksen GF, Fegersten L. The spike wave complex. A clinical correlation. Electroencephalogr Clin Neurophysiol 1959;11:13-22. [20] Loiseau J, Loiseau P, Guyot M, Duche B, Dartigues JF, Aublet B. Survey of seizure disorders in the French Southwest. Y. Incidence of Epileptic Syndromes. Epilepsia 1990;31:391-6. [21] Loiseau P, Duche´ B, Loiseau J. Classification of epilepsies and syndromes in two different samples of patients. Epilepsia 1991;32:303-9. [22] Shah KN, Rajadhyaksha SB, Shah VS, Shah NS, Desai VG. Experience with the International League Against Epilepsy Classification of epileptic seizures (1981) and epilepsies and epileptic syndromes (1989) in epileptic children in a developing country. Epilepsy 1992;33: 1072-7. [23] Ohtsuka Y, Ohno S, Oka E, Ohtahara S. Classification of epilepsies and epileptic syndromes of childhood according to the 1989 ILAE classification. J Epilepsy 1993;6:272-6. [24] Manford M, Hart YM, Sander JWAS. The syndrome classifi-
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cation of the International League Against Epilepsy applied to epilepsy in a general population. Arch Neurol 1992;49:801-8. [25] Oka E, Ishida S, Ohtsuka Y, Ohtahara S. Neuroepidemiological study of chilhood epilepsy by application of international classification of epilepsies and epileptic syndromes (ILAE, 1989). Epilepsia 1995;36: 658-61. [26] Loiseau P. Chilhood absence epilepsy. In: Roger J, ed. Epileptic syndromes in infancy, chilhood and adolescence. London: John Libbey, 1992:135-50. [27] Beaumanoir A. The Lennox-Gastaut syndrome. In: Roger J, ed. Epileptic syndromes in infancy, chilhood and adolescence. London: John Libbey, 1992:115-32. [28] Rodrı´guez Barrionuevo AC, Bauzano Poley E. Sı´ndrome de Lennox-Gastaut. In: Rodriguez AC, ed. Diagno´stico y tratamiento de la epilepsia en la infancia. Madrid: Me´dicos SA, 1995:182-9. [29] Blume WT. Lennox-Gastaut syndrome. In: Lu¨ders H, Lesser RP, eds. Epilepsy: Electroclinical syndromes. London: Springer-Verlag, 1989:73-92. [30] Trevathan E, Murphy CC, Yeargin-Allsopp M. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. Epilepsia 1997;38:1283-8. [31] Wheless JW, Contantinou JE. Lennox-Gastaut syndrome. Pediatr Neurol 1997;17:203-11. [32] Markand ON. Slow spike-wave activity in EEG and associated clinical features: Often called “Lennox” or “Lennox-Gastaut” syndrome. Neurology 1977;27:746-57. [33] Blume WT, David RB, Go´mez MR. Generalized sharp and slow wave complexes. Associated clinical features and long-term followup. Brain 1973;96:289-306.
From the *Pediatric Neurology Unit; Section of Neurology; H.U. de Getafe; †Neurology Unit; Hospital de la Vega Baja; Orihuela, Alicante; ‡Electroencephalography Unit; Section of Neurology; § Pediatric Neurology Unit; Section of Neurology; Hospital 12 de Octubre; Madrid, Spain.
© 2000 by Elsevier Science Inc. All rights reserved. PII S0887-8994(99)00115-0 ● 0887-8994/00/$20.00
Introduction The classification of epileptic seizures is useful in the diagnosis and treatment of patients with epilepsy [1]. However, the seizure type provides only limited information about the prognosis and therapeutic decisions. The International Classification of the Epilepsies and the Epileptic Syndromes [2] considers not only the semiology of the seizures but also other factors, such as the age of onset and the possible etiology. This classification is useful in epileptology, especially for pediatric patients [3]. The generalized spike-and-wave (SW) patterns were first described in a patient with absence seizures [4]. The SW patterns have been differentiated on the basis of their frequency [5-9], and they have been evaluated according to the different pathologic situations associated with them. However, this study is the first to analyze the clinical characteristics of children with epilepsy and the electrical-clinical correlation of the different electroencephalographic patterns in childhood using the international classifications. Subjects and Methods The authors reviewed all of the electroencephalograms (EEGs) (n ⫽ 39,322) performed between January 1980 and December 1990 in the EEG unit of Hospital 12 de Octubre, Madrid, Spain. This hospital serves a population of about 650,000 and was the only center in this area where the technique could be utilized. The SW pattern was observed in 1,068 EEGs from 654 patients, 213 of whom (33%) were younger than 14 years of age. Adequate information was available for only 170 patients, 16 of whom did not have epilepsy and were not included in the present study. The patients who had experienced only febrile seizures were not considered to have epilepsy. The mean follow-up time for the included patients was 4.5 years (S.D. ⫽ 2.86). The patient’s files were reviewed by the same pediatric neurologist, and all relevant information regarding personal and family history, clinical characteristics, and electroencephalographic data was analyzed.
Communications should be addressed to: Dr. Martı´nez-Mene´ndez; U. Neuropediatrı´a; S. Neurologı´a; H.U. Getafe; Ctra de Toledo Km 12,400; 28905-Gefate; Madrid, Spain. Received February 12, 1999; accepted August 26, 1999.
Martı´nez-Mene´ndez et al: Clinical Correlates of Spike-and-Wave Patterns 23
Table 1.
Table 2.
Patients’ histories
Pathologic pregnancy Pathologic delivery Asphyxia Pathologic neonatal period Neonatal seizures Abnormal psychomotor development West syndrome Febrile seizures Head trauma Central nervous system infection Learning difficulties
Common associations of seizures
n
%
Association
n
%
4 16 12 6 3 16 6 22 2 2 28*
2.6 10.4 7.8 3.9 1.95 10.4 3.9 14.3 1.3 1.3 18.2
Absence ⫹ T-C Myoclonic ⫹ T-C SP ⫹ T-C Myoclonic ⫹ Absence CP ⫹ T-C CP ⫹ SP SP ⫹ Sec. generalized
27 22 19 17 8 8 6
17.6 17.5 12.4 11.1 5.2 5.2 3.9
Abbreviations: CP ⫽ Complex partial Sec. ⫽ Secondary
SP ⫽ Simple partial T-C ⫽ Tonic-clonic
* Two of these children presented with progressive mental deterioration.
The 39,322 EEGs had all been recorded with the ALVAR (Paris, France), model XVI TR, with 16 channels, using the 10-20 International System [10], with bipolar and referential montages. All EEGs were reviewed by the same electroencephalographers. The EEG study included background, focal paroxysmal discharges, generalized paroxysmal discharges, with or without focal onset, asymmetric discharges, and association of focal and generalized epileptiform abnormalities. A SW was defined as a generalized paroxysmal discharge, clearly distinguished from background, consisting of a spike followed by a wave [11]. The SWs were classified according to their frequencies into three groups: typical, three cycles per second; slow, less than three cycles per second; and fast, more than three cycles per second. Continuous variables were compared using Student’s unpaired t test. Discrete variables were compared using the chi-square test and odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at P ⬍ 0.05. All probabilities are two-tailed values.
Results The EEGs of 154 children with epilepsy revealed SW patterns. The mean age at seizure onset was 6 years, 6 months (S.D. 3.7; range ⫽ 0-14 years). The mean age at the first EEG was 7 years, 6 months (S.D. 3.6; range ⫽ 0.83-14 years). The sex distribution was about 1:1 (53% females and 47% males). The patients’ medical histories are recorded in Table 1. Eighteen percent of the children had learning difficulties at school, and 14% also had febrile seizures. The family history of epilepsy and febrile seizures was investigated among first-degree
Figure 1. Distribution of frequencies according to the type of first and total seizures. Sec.: secondary.
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and second-degree relatives; 10% of first-degree relatives had epilepsy. The most frequent type of seizure at presentation for the first seizure was absence seizures (35.5%), followed by tonic-clonic seizures (27%), complex partial seizures (14%), secondary generalized seizures (8%), and simple partial seizures (6%) (Fig 1). Two patients (1.31%) presented with complex partial status epilepticus. Only 33 of the patients (21.4%) consulted with physicians after their first seizure; 59% of them had experienced tonic-clonic seizures, 21.9% complex partial seizures, 18.7% secondary generalized seizures, and 3.1% simple partial seizures. Of the 121 children (78.6%) who consulted with physicians after their second seizure, 11 (9.1%) requested medical consultation after a tonic-clonic seizure or an episode of status epilepticus, although they had previously had absence or partial seizures. More than 40% of the patients had several types of seizures. The global distribution of seizures (Fig 1) was different than the distribution of the first seizures. The most common type was tonic-clonic seizures (48%), followed by absence seizures (46%), complex partial seizures (20.5%), myoclonic seizures (18%), and simple partial seizures (18%). Thirteen children (8.4%) had status epilepticus of one type or another at some time during their illness. The most common associations of seizures were absence seizures or myoclonic seizures with tonicclonic seizures (Table 2). The classification of the patients according to the
⫽ 2.98) or fast SW patterns (mean ⫽ 7 years, S.D. ⫽ 3.9) (P ⬍ 0.001). The typical SW pattern was associated with learning difficulties less frequently than the other SW patterns (OR ⫽ 0.33; 95% CI ⫽ 0.12-0.92%). The typical SW pattern was usually associated with only one type of seizure (OR ⫽ 3.3; 95% CI ⫽ 1.57-6.92%), especially absence seizures (OR ⫽ 13.7) (Tables 3 and 4). The neurologic examination was usually normal (OR ⫽ 4.25; 95% CI ⫽ 1.65-12.3%) as was the cranial computed tomography (CT) scan (OR ⫽ 15.6; 95% CI ⫽ 1.48101%). The typical SW pattern was mainly associated with the idiopathic generalized epilepsies (OR ⫽ 9.24) and had the best outcome (Tables 3 and 4). The slow SW pattern was associated with West syndrome (OR ⫽ 37.1; 95% CI ⫽ 4.11-335%), pathologic pregnancy (OR ⫽ 7.69; 95% CI ⫽ 1.43-50%), abnormal psychomotor development (OR ⫽ 7.14; 95% CI ⫽ 2.520%), learning difficulties (OR ⫽ 6.1; 95% CI ⫽ 2.3515.7%), and the presence of more than one seizure type (OR ⫽ 5.25; 95% CI ⫽ 1.96-14.28%), especially atonic, myoclonic, tonic, and partial seizures (Tables 3 and 4). The neurologic examination and cranial CT scan were abnormal more frequently (OR ⫽ 7.69; 95% CI ⫽ 3.13-20% and OR ⫽ 54; 95% CI ⫽ 6.25-500%, respectively) than with other SW patterns. The slow SW pattern was primarily associated with symptomatic partial epilepsies (OR ⫽ 25.2), cryptogenic or symptomatic generalized
Figure 2. Distribution of frequencies according to epileptic syndromes. Sec: secondary. Special S.: special syndrome; PGE: uncertain epilepsies between partial or generalized; SGE: symptomatic generalized epilepsies; CSGE: cryptogenic or symptomatic generalized epilepsies; IGE: idiopathic generalized epilepsies; CPE: cryptogenic partial epilepsies; SPE: symptomatic partial epilepsies; IPE: idiopathic partial epilepsies.
International Classification of Epileptic Syndromes (Fig 2) was as follows: idiopathic generalized epilepsy (49%), cryptogenic partial epilepsy (13%), idiopathic partial epilepsy (8%), undetermined whether partial or generalized (8%), cryptogenic or symptomatic generalized (8%), special syndromes (8%), symptomatic partial epilepsy (3%), and symptomatic generalized epilepsy (3%). Children with slow SW patterns were younger at the onset of seizures (mean ⫽ 3.7 years, S.D. ⫽ 3.17) than children with typical SW patterns (mean ⫽ 7.1 years, S.D.
Table 3.
Seizure types, epileptic syndromes, and outcomes according to SW pattern correlation
Seizure types Absence Tonic-clonic Tonic Myoclonic Atonic Simple partial Complex partial Secondary generalized Epileptic syndromes IPE SPE CPE IGE CSGE SGE PGE Special syndromes Outcomes Seizure free Recurrence
OR
Typical SW 95% CI
OR
95% CI
OR
95% CI
13.7 0.16 0.34 0.19 0.05 0.27 0.27 0.27
5.99-31.3 0.08-0.35 0.04-2.99 0.05-0.65 0.01-0.77 0.09-0.83 0.1-0.76 0.08-0.97
0.68 1.64 5.95 6.37 26.2 4.2 1.03 0.93
0.28-1.67 0.68-3.96 1.13-31.5 2.42-16.8 7.3-94.3 1.58-11.2 0.35-3.03 0.25-3.47
0.12 3.68 0.53 0.91 0.36 0.99 2.8 5.77
0.06-0.25 1.88-7.21 0.94-2.97 0.39-2.13 0.11-1.18 0.42-2.36 1.21-6.42 1.58-21
0.558 0.274 0.164 9.24 0.061 1.43 0.863 0.325
0.14-2.15 0.03-2.33 0.04-0.73 4.19-20.4 0.01-0.92 0.37-5.55 0.25-3.01 0.07-1.53
0.46 25.2 0.206 0.228 24.8 3.76 1.87 0.357
0.06-3.73 2.68-237 0.03-1.6 0.08-0.65 6.04-102 0.59-23.8 0.47-7.49 0.045-2.86
2.34 0.264 12.8 0.306 0.338 1.67 1.89 6.21
0.67-8.15 0.03-2.42 2.88-57.6 0.157-0.6 0.09-1.3 0.27-10.3 0.43-8.21 1.31-29.4
9.15 0.151
2-41 0.29-0.77
0.15 0.3
0.05-0.42 0.04-2.74
Abbreviations: CI ⫽ Confidence interval CPE ⫽ Cryptogenic partial epilepsies CSGE ⫽ Cryptogenic or symptomatic generalized epilepsies IGE ⫽ Idiopathic generalized epilepsies IPE ⫽ Idiopathic partial epilepsies
Slow SW
OR PGE SGE SPE SW
⫽ ⫽ ⫽ ⫽ ⫽
Fast SW
0.9 11.8
0.4-2.05 2.32-61
Odds ratio Uncertain epilepsies between partial and generalized Symptomatic generalized epilepsies Symptomatic partial epilepsies Spike-and-wave
Martı´nez-Mene´ndez et al: Clinical Correlates of Spike-and-Wave Patterns 25
Table 4.
Variables associated with the typical, slow, and fast SW
Typical SW Absence of learning difficulties Single type of seizure Absence seizures (inversely associated with the rest of seizure types) Normal neurologic examination Normal cranial CT scan Idiopathic generalized epilepsy Control of seizures with monotherapy Seizure free Absence of recurrence after drug withdrawal Slow SW Pathologic pregnancy Psychomotor developmental abnormalities Learning difficulties West syndrome More than one type of seizure Younger age at seizure onset Atonic, myoclonic, tonic, and partial simple seizures Normal neurologic examinaton Abnormal cranial CT scan Cryptogenic or symptomatic generalized epilepsy or symptomatic partial epilepsy Polytherapy Poor control of seizures Absence of recurrence after drug withdrawal Fast SW Partial seizures with secondary generalization, tonic-clonic, and partial complex seizures Normal cranial CT scan Cryptogenic partial epilepsies or isolated seizures Recurrence of seizures after drug withdrawal Abbreviations: CT ⫽ Computed tomography SW ⫽ Spike-and-wave
epilepsy (OR ⫽ 24.8) (Tables 3 and 4), and poor seizure control (Tables 3 and 4). The fast SW pattern was associated with tonic-clonic, partial complex, and secondary generalized seizures but was infrequently associated with absence seizures (Tables 3 and 4). The fast SW pattern was also associated with normal cranial CT (OR ⫽ 3.55; 95% CI ⫽ 1.14-11.11%) and cryptogenic partial epilepsy (OR ⫽ 12.8) (Tables 3 and 4). Patients with a fast SW pattern had the highest risk of recurrence (Tables 3 and 4). It was not possible to demonstrate an association between the different discharge types and some of the studied variables (sex, childbirth type, asphyxia, pathologic neonatal period, neonatal seizures, febrile seizures, head trauma, infections of the central nervous system, family history of epilepsy, family history of febrile seizures, and other EEG variables). Discussion The present study covers the entire pediatric age group. The age distribution at the onset of seizures demonstrated a higher rate of onset in the first year, a smaller rate of onset in the second year, and similar rates in the following years. Other investigators obtained a similar age distribu-
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tion among patients with epilepsy in general [12-16]. The rate of epilepsy onset is considered to be highest in the first year after birth and gradually declines after 10 years of age [16,17]. In this study the incidence of epilepsy in the children with SW patterns declined after 8 years of age. We intuitively linked SW patterns to absence seizures. In fact, this seizure type was the most frequent one of the first seizures in this study (36%), but tonic-clonic seizures were more common in the whole series (44%), and even partial seizures accounted for 37% of seizures. A great number of children had several types of seizures. The most frequent associations were absence and tonic-clonic seizures and myoclonic and tonic-clonic seizures. Nineteen percent of the patients with SW patterns had only partial seizures. It is difficult to compare the results of this study with previous ones because of methodologic problems. In general terms, all the seizure types had a higher frequency in the classic works [18,19]. However, in the study of Silverman, [18] partial seizures were almost nonexistent, and in the study of Lunndervold et al. [19] the frequency of partial seizures was important. Gastaut [8] in his study of generalized SW bursts did not even mention partial seizures. When the distribution of the frequencies of the different epileptic syndromes was analyzed [2], 60% of them were classified as generalized and nearly 50% were considered idiopathic, but almost 25% were partial epileptic syndromes. It was difficult to differentiate between partial and generalized in 8% of the patients, and the remaining 8% were special syndromes. The authors could not compare these results with other studies because, to their knowledge, no equivalent study has been published. Among patients with epilepsy in general, however, partial epilepsies predominate, and a great variability exists with regard to the uncertain epileptic syndromes and special syndromes [17,20-25]. The correlation of the three different types of SW patterns with the clinical characteristics and outcome of the patients is not well established. According to Gastaut [8] the presence of a family history of epilepsy was frequent in patients with typical SW patterns, relatively frequent in persons with fast SW patterns, and uncommon in patients with slow SW patterns. However, the authors could not demonstrate any association between the type of SW pattern and variables, such as sex, childbirth type, asphyxia, febrile seizures, neonatal seizures, head trauma, or central nervous system infections; all were associated in the classic studies with the slow SW pattern [8,19]. No series of patients with different SW types has been published to date. For this reason, we could only compare data with infantile absence seizures or the Lennox-Gastaut syndrome. Standard textbooks state that absence seizures are more frequent in girls, that a family history of epilepsy is common, and that the patient’s personal medical history is irrelevant. On the other hand the Lennox-Gastaut syndrome is more frequent in males without a family history of epilepsy, and frequently the investigators discovered significant medical diseases in the patient’s med-
ical history [26-28]. However, as stated previously, we did not encounter these associations with the typical SW and slow SW patterns. In the present study the only variables that were associated with a SW pattern were pathologic pregnancy (eight times more common in the children with a slow SW pattern), retarded psychomotor development (eight times more common in the patients with a slow SW pattern), personal history of West syndrome (37 times more frequent in the children with a slow SW pattern), and learning difficulties. The slow SW pattern has generally been related to the Lennox-Gastaut syndrome [28-31]. The association of the slow SW pattern with West syndrome is also well known, although it had not been previously quantified. Learning difficulties are associated with the slow SW pattern in the same way as they are with the Lennox-Gastaut syndrome [6,7,30-33], in which intellectual deficits appear in a high percentage of patients. When the age at which the first seizures occurred was analyzed, we observed that seizures began at a younger age in children with a slow SW pattern than in children with typical or fast SW patterns. The slow SW pattern was also associated with a child having more than one seizure type (OR ⫽ 5) and with atonic seizures (OR ⫽ 26), myoclonic seizures (OR ⫽ 6), tonic seizures (OR ⫽ 6), and simple partial seizures (OR ⫽ 4). The authors documented a strong correlation between the slow SW pattern and cryptogenic or symptomatic generalized epilepsy (OR ⫽ 25), which demonstrates the association of this EEG pattern with the Lennox-Gastaut syndrome and confirms the findings of the classic works [6,33] by statistical methods. This correlation was not unique because the slow SW pattern also had a similar association with symptomatic partial epilepsies. As is widely known, absence seizures are associated with the typical SW pattern. The authors determined a strong correlation between the typical SW pattern and the presence of absence seizures (OR ⫽ 13.7) and idiopathic generalized epilepsies (OR ⫽ 9.2). The results of cranial CT paralleled those of the neurologic examination (i.e., normal results in the typical and fast SW patterns and abnormal in the slow SW pattern). The data regarding the fast SW pattern may be more interesting because they are less well known. The fast SW pattern was associated with secondary generalized partial seizures (OR ⫽ 6), tonic-clonic seizures (OR ⫽ 4), and partial complex seizures (OR ⫽ 3). Cranial CT was usually normal. The fast SW pattern was also associated with the cryptogenic partial epilepsies and the isolated seizures and was inversely associated with the idiopathic generalized epilepsies. We observed an association between slow and fast SW patterns and partial epilepsy. The slow SW pattern was not only associated with cryptogenic or symptomatic generalized epilepsy but also with symptomatic partial epilepsy. This association of SW patterns and partial epilepsies is especially intense in the case of the fast SW pattern, in
which the association is only demonstrated with partial epilepsies and isolated seizures. That children with a typical SW pattern were almost 10 times as likely to be seizure free and had few recurrences (OR ⫽ 0.15) than those children with atypical SW patterns may indicate that it is a more benevolent illness. In this study the possibility of children with a slow SW pattern to be free of seizures was scarce (OR ⫽ 0.15). However, if they were able to be without medication the possibility that their illness would not recur was higher. Children with a fast SW pattern had a higher risk of recurrence (OR ⫽ 12). In conclusion, although generalized epilepsies predominate among children with epilepsy associated with SW patterns, a significant number of these patients suffer from partial epilepsies. The epilepsy of children with a typical SW pattern can be considered benign in contrast to the epilepsy of children with a slow SW pattern, which can be considered malignant. The epilepsy course of children with a fast SW pattern can be difficult to predict because the pattern was associated with either isolated seizures or seizure recurrence.
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