The National General Practice The

Syndromic Classification of the International League Against Epilepsy Applied to Epilepsy in a General Population

Mark Manford, MRCP; Yvonne M. Hart, MRCP; Josemir W. A. S.

this prospective, population-based study of 594 cases of newly diagnosed epilepsy, proportions in categories as defined by the International League Against Epilepsy (ILAE) were as follows: (1) localization-related epilepsies: 1.1* idiopathic, 1.2%; 1.2* symptomatic, 16.2%; and 1.3 cryptogenic, 24.6%; (2) generalized epilepsies: 2.1* idiopathic \s=b\ In

(idiopathic generalized epilepsy) with 3-Hz spike and wave: absence epilepsy, 2.2%;juvenile myoclonic epilepsy, 1.5%; and nonspecific idiopathic generalized epilepsy, 5.6%; symptomatic generalized epilepsies, 1.5%; 2.3.2* specific syndromes with generalized epilepsy, 0.3%; 3.2 seizures without unequivocal focal or generalized features, 32%; 4.1 situation-related syndromes, isolated seizures, 2.3.1*

9.9%; seizures due

Only 33.6%

to acute toxic

in

or

metabolic cause,*

diagnostic ILAE categories (asterisks) and many rare syndromes were not represented. The remainder (66.4%) were in various nonspecific categories. Only 24% of localization-related epilepsies could be clinically localized to a single ILAE-proposed site of origin and of these best localized cases, 14% had strongly discordant imaging or electroencephalograms. These major problems in applying the ILAE classification to epilepsy in the general population and its underemphasis of modern imaging techniques are discussed. 4.5%.

were

(Arch Neurol. 1992;49:801-808)

shared and distinctive features of remains a fundamental principle in their and is essential for coherent investigation. The International League Against Epilepsy (ILAE) pro¬ posed a basic division of epilepsies1-2 that was refined re¬ cently3 to include numerous, narrowly defined syndromes and several nonspecific categories into which all general¬ ized and partial epileptic seizures should fall (Table 1). The

recognition of The diseases classification

idiopathic generalized epilepsies (IGE) are classified based

the age of onset and combination of seizure types. Par¬ tial seizures are attributed to restricted sites of the cerebral cortex, predominantly according to their clinical features (Table 2), with supportive evidence from electroencephaon

Accepted

Study of Epilepsy

for publication April 6, 1992. From the Chalfont Centre for Epilepsy, Buckinghamshire, England. Reprint requests to Chalfont Centre for Epilepsy, Chalfont St Peter, Gerrards Cross, Buckinghamshire, England SL9 ORJ (Dr Manford).

Sander, MD; Simon

D.

Shorvon,

FRCP

lography (EEG), although it is acknowledged that many partial seizures occur in the absence of specific interictal, and sometimes also ictal, EEG change. The principles were established based on the literature, ictal telemetry record¬ ings, and the experience of a panel of experts, all sources derived primarily from patients seen in referral centers. Patients attending these centers may represent a selected and atypical group; in particular, those referred for con¬ sideration of focal surgery may have more easily localiz¬

able seizures than patients elsewhere. If the model is to be meaningful in pathophysiologic and clinical terms, it should account for all seizures, not only those occurring in patients with severe disease, patients from tertiary referral centers, or refractory patients. The National General Practice Study of Epilepsy (NGPSE) is a prospective, population-based incidence study, identifying patients at the time of first diagnosis, avoiding the potential bias of hospital-based studies.4"6 By attempting to categorize these cases according to the ILAE classification, this study aims to do the following: to iden¬ tify the proportion of epilepsy in the general population that falls into the clearly defined syndromes or the nonspecific categories of the ILAE; to estimate the relative incidence of different ILAE syndromes; to assess the clin¬ ical criteria of the ILAE for anatomic localization of localization-related epilepsies; to identify cases with dis¬ cordance of localization by clinical, EEG, and imaging methods; and to review the criteria for defining epileptic syndromes. In addition to discussing epileptic syndromes, patients are also categorized by seizure type, as defined by the ILAE,2 and by seizure etiology. METHODS

study have been described general practitioners notified the

Details of the methods of the

elsewhere.4"6 In summary, 275

study of all patients older than 1 month old in whom a new di¬ agnosis of definite or possible epileptic seizures was made dur¬ ing a 3-year prospective recruitment phase. The practices were

located around the country in urban and rural areas to avoid de¬ mographic sources of bias. Patients were followed up by the study at 6 months and then at yearly intervals; to date, follow-up is from 4 to 7 years. Details of hospital and specialist assessment and re¬ sults of investigations were also obtained. The study population is thus an unselected cohort of patients with newly diagnosed epilepsy, identified at general population level, in whom com-

Table 1.—Patients

Grouped According to the International League Against Epilepsy Classification of Epileptic Syndromes2 No. of Cases (%)

epilepsies

1

Localization-related

1.1

Idiopathic (with age-related onset)

252(31)

Benign childhood epilepsy with centrotemporal spikes Childhood epilepsy with occipital paroxysms

1.2

1.3 2

Primary reading epilepsy Symptomatic Chronic progressive epilepsia partialis continua of childhood Syndromes characterized by seizures with specific modes of precipitation Temporal, frontal, parietal, and occipital lobe epilepsies Cryptogenic Temporal, frontal, parietal, and occipital lobe epilepsies Generalized epilepsies and syndromes

2.1

Idiopathic (with age-related onset) Benign myoclonic epilepsy in infancy Childhood absence epilepsy/juvenile absence epilepsy* Juvenile myoclonic epilepsy (impulsive petit mal) Epilepsy with generalized tonic-clonic seizures on awakening Syndromes characterized by seizures with specific modes of precipitation Other idiopathic generalized epilepsies

2.2

Cryptogenic

or

symptomatic (in order of age)

West syndrome (infantile spasms) Lennox-Gastaut syndrome Epilepsy with myoclonic astatic seizures Epilepsy with myoclonic absences

2.3 2.3.1

2.3.2 3

3.1

3.2 4 4.1

Symptomatic Nonspecific etiology Early myoclonic encephalopathy Early infantile epileptic encephalopathy with suppression burst Other symptomatic generalized epilepsies Epilepsies due to specific neurologic diseases Epilepsies undetermined whether focal or generalized With both generalized and focal seizures Severe myoclonic epilepsy in infancy Epilepsy with continuous spike waves during slow wave sleep Acquired epileptic aphasia (Landau-Kleffner syndrome) Other undetermined epilepsies Without unequivocal focal or generalized features Special syndromes Situation-related epilepsies Febrile convulsions Isolated seizures or status epilepticus Seizures due to an acute toxic or metabolic event

7 (0.9) 0 (0) 0 (0)

96(11.8) 0 (0) 0 (0) 96 (11.8) 146 (17.9)

66(8.1) 55 (6.8) 0 (0) 1 3 (1.6) 9 (1.1) 0 (0) 0 (0) 33 (4.1) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 11 (1.4)

0 0 0 9

(0) (0) (0) (1.1) 2 (0.2) 190(23.3) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 190(23.3) 306 (37.6) 220 (27.0) 59 (7.2) 27 (3.3)

Total 814(100) "Classified separately in the International League Against Epilepsy classification. Seizures occurring before 1 month of age were excluded from the National General Practice Study of Epilepsy, including benign neonatal convulsions (category 2.1), benign neonatal familial convulsions (cat¬ egory 2.1), and neonatal seizures (category 3.1).

prehensive clinical details have been obtained. Considerable em¬ phasis in the design of the study was placed on avoiding sources of selection bias in the identification of the study group and in obtaining comprehensive clinical data from primary and second¬ ary care sources; the study has been uniquely successful in these regards. We believe, therefore, that the study group is truly rep¬ resentative of newly diagnosed epilepsy as it occurs in a general population. A total of 1195 patients were notified to be in the study and were classified by the study panel.5 Of these, 104 were excluded because of previously diagnosed epilepsy or neonatal seizures. Seventy-nine cases were diagnosed as nonepileptic seizure disor¬ ders, mostly syncope or psychogenic attacks, and a further 198 cases of possible, but not definite epilepsy, are excluded from this analysis. Two hundred twenty had febrile seizures and the remaining 594 patients were classified as having definite epilep-

represents a small increase in the number of definite cases of epilepsy in the NGPSE since previous reports,5'6 because of reclassification of some previously uncertain cases, in the light of new data. Patients' characteristics are given in more detail by Sander et al.5 These 814 patients were categorized according to the ILAE classification of epileptic syndromes,3 ap¬ plying criteria summarized in Table 3. Localization-related sei¬ zure origin was classified as conforming to a single ILAE category, a region constituting two or more neighboring ILAE categories, as lateralizable, or as unrealizable within the ILAE classification (Table 2). Patients were also categorized by seizure type according to the ILAE classification2 and by seizure etiology. Etiologic factors were classed as definitely significant, eg, glioma, or probably significant, eg, moderate perinatal trauma. Vascular disease was accepted only as definitely significant where there was a clear history of central nervous system vascular tic seizures. This

Table

2.—Summary of the International League Against Epilepsy Classification of Manifestations2 Localization-Related Seizure

Region Supplementary motor

Clinical Seizure Pattern

Cortical

Cingulate

Frontopolar Orbitofrontal Dorsolateral (premotor

cortex)

Opercular

Postural, simple focal

motor

Mesial

temporal

Lateral

temporal

Parietal

Occipital

Mastication, salivation, swallowing, and speech

arrest with epigastric aura, fear, and autonomie phe¬ ipsilateral and gustatory hallucination is common Contralateral tonoclonic movements according to somatotopy, speech arrest, and swallowing with fre¬ quent generalization; ipsilateral leg involved in paracentral seizures Autonomie or psychic phenomena with gustatory or olfactory sensations and epigastric sensations; in complex partial seizures; speech and motor arrest with oroalimentary automatism As mesial temporal with additional somatosensory, visual, or auditory manifestations Somatosensory manifestations and loss of muscle tone, with intra-abdominal sensations; visual mani¬ festations are often formed hallucinations; sometimes negative sensory phenomena Visual hallucinations, formed or unformed, with eye and head movements and distorted visual percep¬

partial clonic facial

seizures may be

tion

events—stroke or transient ischemie attack—or evidence of cere¬ brovascular disease on neuroradiologic imaging. Extracranial vascular diseases, eg, myocardial infarction, were considered probable or possible indicators of cerebrovascular disease (see Sander et al5).

RESULTS

Classification of Epileptic Syndromes (Table 1) Localization-Related Epilepsies (Categories 1.1, 1.2, and 1.3).—Two hundred forty-five patients experienced epilepsy that was localization related based on clinical features or EEG findings. Of these, 14 had strong EEG ev¬ idence of partial onset without any focal clinical clues; in 10 the EEG showed temporal spikes. An additional seven patients were included in this category who had general¬ ized seizures with no historical clues and an unremarkable EEG but focal abnormalities on computed tomographic

(CT)

scan.

Benign epilepsy with centrotemporal spikes (BECT) was strongly suspected in seven children based on electroclinical features, although not all had undergone sleep studies or neuroimaging. No other idiopathic, partial epilepsies

identified. A cause was identified in 39.2% of the other 245 cases of localization-related epilepsies. Generalized Epilepsies (Category 2.1).—In 41 patients, a diagnosis of IGE, with 3-Hz spike and wave, could be made based on a typical appearance of the EEG, associated with generalized seizures (Table 4). In only 19 of these was there a cluster of seizure types that allowed a syndromic classification to be made. A further three patients had a clinical picture suggestive of juvenile myoclonic epilepsy, but EEG data were absent or nonspecific. One girl, aged 4 years, had absence seizures with an EEG suggesting but not diagnostic of IGE, and 10 patients had tonoclonic sei¬ zures, with an EEG suggesting a generalized epilepsy, without the classic 3-Hz appearance. The remaining 22 patients had a typical 3-Hz EEG appearance but experi¬ enced only tonoclonic seizures, with no particular diurnal were

vocalization, speech arrest, fencing, and complex focal with urinary

Complex focal with initial automatisms with sexual features, vegetative signs, changes in mood and af¬ fect, and urinary incontinence Initial loss of contact, adversive and subsequent contraversive movements of head and eyes, axial clonic jerks, falls, and autonomie signs with frequent generalized tonoclonic seizures Complex focal with initial automatisms or olfactory hallucinations, autonomie signs, and urination Simple focal tonic with versive movements and aphasia and complex focal with initial automatisms nomena;

Primary

tonic with

incontinence

in five of these patients there was only a single seizure during the follow-up period. Of 13 patients with absence epilepsy, 10 (77%) were fe¬ male. Other types were nearly evenly distributed between the sexes. The age of onset of absence epilepsy ranged from 4 to 15 years and was significantly younger than the onset of IGE without absences (P