ORIGINAL ARTICLE

Clinical characteristics and use of antiepileptic drugsamong adolescents with uncomplicated epilepsy at a referralcenter in Novi Sad, Serbia

Ksenija Gebauer-Bukurov • Ksenija Bozic •

Slobodan Sekulic

Received: 7 June 2011 / Accepted: 3 August 2011 / Published online: 26 January 2012

� Belgian Neurological Society 2012

Abstract The study aimed to investigate the type and

etiology of epileptic seizures and the use of antiepileptic

drugs for the treatment of various forms of epileptic sei-

zures among adolescents with active but uncomplicated

epilepsy at a tertiary referral center in Novi Sad, Serbia.

The study design was cross sectional. Data were obtained

from patients and medical records. A total of 103 adoles-

cents (39 males and 64 females) with active but uncom-

plicated epilepsy were included. Patients with primary

generalized seizures had significantly better control of

epilepsy than those with partial seizures with or without

secondary generalization. A total of 80 (77.7%) adoles-

cents had no known underlying etiology based on initial

diagnosis and evaluation. All adolescents were classified

into known idiopathic syndromes (54.4%), non-classifiable

cryptogenic etiology (23.3%), and secondary epilepsy

attributed to MRI-identified lesions (22.3%). Eighty-eight

percent of adolescents were taking monotherapy and 64.8%

of these were taking valproate. New antiepileptic drugs

(AEDs), topiramate and lamotrigine, the only drugs avail-

able free of charge at the Serbian market, were used in

19.4% of patients. A total of 57.3% adolescents were sei-

zure-free, 24.2% had occasional seizures, and 18.5% had

seizures despite AED treatment.

Keywords Adolescents � Epilepsy � Seizure � Seizure

control � Antiepileptic drugs

Introduction

In the recent literature, there are few studies of adolescents

with chronic diseases; adolescents are rarely observed as a

separate group and more frequently as part of adult or

pediatric populations.

Studies of epilepsies in adolescents have shown that this

period often means changes in the epilepsy itself, diffi-

culties in controlling seizures, and poor compliance [1, 2].

The risk of social isolation and stigmatization that can have

a negative impact on quality of life is higher in adolescents

and young adults. Seizure control can thus be especially

important for this group of patients, although sometimes

difficult to achieve.

Choice of treatment for epilepsy is influenced by many

factors. These include efficacy of different drugs in dif-

ferent seizure types and syndromes, tolerability, factors

related to the characteristics of the patients, cost-benefit

ratio, and also drug availability in the country [3, 4].

The current treatment of epilepsy includes a variety of

older and newer antiepileptic drugs (AEDs). The new AEDs

have been shown in clinical studies to offer important

improvements in the safety, side-effect profile, and risk of

interactions. Several clinical trials have demonstrated that

new agents offer similar efficacy compared with ‘‘old AEDs’’

[5–8]. New AEDs are usually investigated as an add-on

therapy in randomized clinical trials and, therefore, labeled as

second-line therapy. At the time the study was conducted,

there were only two new AEDs (topiramate and lamotrigin)

available free of charge at the Serbian market, and one more

(levetiracetam) was introduced in 2010. According to the

recommendations of the Serbian Medical Products Agency,

new AEDs are used if treatment with conventional and

cheaper AEDs has failed. A similar approach is taken in

several developed countries in Europe [9].

K. Gebauer-Bukurov (&) � K. Bozic � S. Sekulic

Department of Child Neurology and Epilepsy,

Clinic for Neurology, Clinical Center of Vojvodina,

Hajduk Veljka 1, 21 000 Novi Sad, Serbia

e-mail: gebauerbukurov.ksenija@gmail.com

123

Acta Neurol Belg (2012) 112:147–154

DOI 10.1007/s13760-012-0008-2

The aim of the study was to investigate the type and

etiology of epileptic seizures, and utilization of AEDs for

the treatment of various forms of epileptic seizures among

adolescents with active but uncomplicated epilepsy in a

tertiary referral center in Novi Sad, Serbia, and to compare

the drug utilization pattern with those from other countries.

Methods and materials

Definitions

Uncomplicated epilepsy was defined as epilepsy with no

initially associated neurological impairment and mental

retardation. The diagnosis of epilepsy was defined as a his-

tory of at least two unprovoked epileptic seizures. In order to

take part in the study, an adolescent should have had at least

one epileptic seizure during the previous 5 years (active

epilepsy) and been taking AEDs for at least 12 months. The

classification of epileptic seizures and syndromes was based

on the clinical semiology and electroencephalographic

(EEG) findings according to the International League

Against Epilepsy guidelines (Commission on Classification

1989) [10]. The patients were categorized by etiology into

three groups: symptomatic, cryptogenic, and idiopathic.

Idiopathic epilepsies are characterized by their age-related

onset, clinical and EEG characteristics, and a presumed

genetic etiology. There are childhood absence epilepsy,

juvenile myoclonic epilepsy, juvenile absence epilepsy, and

‘‘other generalized epilepsy’’. Cryptogenic refers to epilepsy

in which there is no identifiable underlying etiology and the

form of epilepsy is not one of the specific idiopathic syn-

dromes. Symptomatic etiology refers to brain disorder

associated with an increased risk of epilepsy confirmed on

magnetic resonance imaging (MRI). Classification of sei-

zures control was based on the type and number of seizures

experienced in the past 12 months [11]:

1. Good control–no seizures during the past 12 months

2. Partial control–low seizure frequency: 1–20 simple

partial or 1–4 complex partial or 1 GTK or 1–20

absence or 1–20 myoclonic seizures

3. Poor control–high seizure frequency: [20 simple

partial or [4 complex partial or [1 GTK or [20

absence or [20 myoclonic seizures.

Adolescents were defined as youth from 12 to 22 years

of age. We included young persons aged 18–22 years in the

sample since they were still followed-up at our department

of child neurology and the majority still lived with their

parents and were attending school.

Novi Sad is the capital and regional center of the

Autonomous Province of Vojvodina, with a total area of

235.6 km2. The population of Novi Sad in 2002 was

299,294 with approximately 40,000 in the age group

12–22. The city has a Children’s University Hospital pro-

viding care and treatment of inpatients and outpatients aged

0–18 years, and a University Hospital with a child neu-

rology department at the Clinic for Neurology, treating

children over 4 years of age and adolescents and young

adults under the age of 25. The study was carried out at the

Department of Child Neurology of the Clinic for

Neurology.

Subjects

The study was cross sectional. Study subjects were ado-

lescents aged 12–22 with the diagnosis of epilepsy, who

were admitted as inpatients or outpatients at the Clinic for

Neurology, Department of Child Neurology, during the

period from July 1, 2007 to July 1, 2008. The majority of

patients were treated in our center from the beginning and

some of the patients were previously treated at the Chil-

dren’s University Hospital. The data were collected from

medical records and clinical examinations. Detailed histo-

ries were obtained from all patients and their parents. Each

patient underwent EEG with a 16-channel recorder using

the international 10–20 system, routinely including 5 min

of hyperventilation and photic stimulation, and sleep record

when needed. Computed tomography (CT) and/or MRI

were performed in all partial seizures and in all patients in

whom a structural lesion was suspected. A detailed analysis

of epilepsies and epileptic syndromes was made in all

patients. Exclusion criteria were additional neurological

impairment and mental retardation. A structured protocol

was used to collect the following clinical information:

• demographic data

• age at onset and duration of epilepsy

• seizure type (clinical and EEG finding)

• etiology

• seizure frequency

• AED treatment (mono or polytherapy, new or

conventional AEDs).

Results were recorded in both EXCELL and SPSS 11.0

for Windows. The analysis was completed using SPSS.

Groups of adolescents were compared for significance

using the Chi-square statistical test, and p \ 0.05 was

considered statistically significant.

Results

A total of 103 adolescents (39 males and 64 females) were

observed for epilepsy during the study period.

Dominant seizure types were primary generalized tonic–

clonic seizures (TCS) (40.7%), followed by partial seizures

148 Acta Neurol Belg (2012) 112:147–154

123

with secondary generalization (19.4%). In only one case

the seizure type could not be classified. Distribution of

seizure types by gender, age, duration of epilepsy, seizure

control, usage and range of prescribed daily dosage (PDD)

of AEDs are shown in Table 1.

Fifty-nine adolescents (57.3%) were seizure free,

25 (24.2%) had occasional seizures, and 19 (18.5%) had

seizures despite AED treatment.

A total of 80 out of 103 adolescents (77.7%) had no

known underlying etiology, based on initial diagnosis and

evaluation. According to clinical and EEG findings, 56

(70%) patients out of 80 had idiopathic syndromes and

therefore idiopathic etiology. Childhood absence epilepsy

(CAE) was identified in 4 (7.1%), juvenile absence epi-

lepsy (JAE) in 7 (12.5%), and juvenile myoclonic epilepsy

(JME) in 12 (21.4%). However, the most frequent epileptic

syndrome was epilepsy with generalized TCS on awaken-

ing, seen in 19 (33.9%) cases. In 14 (25%) patients with

idiopathic generalized epileptic (IGE) syndromes, there

was a clear clinical history as well as generalized EEG

discharges of primary generalized seizures. All of these

patients had a normal MRI and were classified as ‘‘other

primary generalized epilepsies not defined above’’. A

majority of the patients with IGE (71.4%) achieved com-

plete seizure control.

The remaining 24 patients (30%) had cryptogenic eti-

ology with no identifiable underlying etiology, and the

form of epilepsy, based on clinical and EEG findings, could

not be classified as one of the specific idiopathic syn-

dromes. Complete seizure control was achieved in 41.7%

of those patients.

According to positive MRI findings, 23 out of 103

patients (22.3%) were classified as symptomatic etiology

and 37.5% of these were seizure free. Seizure control

results in relation to underlying pathologies are shown in

Table 2.

No differences between the three epilepsy subgroups

(idiopathic, cryptogenic and symptomatic) were observed

regarding gender (v2 = 1.745, p = 0.418) and duration of

epilepsy (v2 = 7.001, p = 0.537). The groups did, how-

ever, differ in control of seizures (v2 = 10.707, p = 0.030)

and the use of AEDs (v2 = 14.402, p = 0.001) (Table 3).

Eighty-eight percent of all studied adolescents were

taking monotherapy and 64.8% of these were taking val-

proate. New AEDs, topiramate and lamotrigine, were used

by 20 (19.4% of all patients), and by 12 in monotherapy.

The patients on monotherapy had significantly better con-

trol of epilepsy than those on polytherapy (v2 = 15.514,

p = 0.000). Complete seizure control was achieved in 11

patients (55%) on new AEDs. However, there was no

significant difference in control of epileptic seizures

between patients on conventional and those on new AEDs.

Except one, all patients with IGE were on monotherapy.

The use of AEDs in relation to age, duration of epilepsy (in

years), etiology, and seizure control are summarized in

Table 4.

Discussion

This study aimed to provide a cross-sectional view of the

characteristics of epilepsy among adolescents in an epi-

lepsy referral center in Serbia. In the epilepsy literature

there are few studies focusing on adolescents, although this

period often means changes in the epilepsy condition and

difficulties in controlling epilepsy. Chronic disease and its

treatment put extensive behavioral demands on adoles-

cents. Adolescents with chronic illness are forced to con-

sider the limitations resulting from their illness. They are

rarely seen as a separate age group, but are considered as

either children or adults. This can cause difficulties in

unveiling the special needs and problems related to ado-

lescence. Our neurology clinic is primarily a clinic for

adult patients, comprising one children’s department where

the majority of adolescents with epilepsy are treated. For

this reason, we support those authors that advocate the need

for special adolescent clinics in order to meet the special

needs of adolescents with chronic disorders such as epi-

lepsy. Adolescent epilepsy per se should not be more dif-

ficult to control than epilepsy in other age groups.

Most prevalence studies on epilepsy in children show a

dominance of boys [12–15]. However, the dominance of

girls that was found in the present study is in agreement

with other reports dealing with specific childhood ages and

studies of IGEs [16–18].

We found that the ILAE system was useful in classify-

ing our patient population. We were able to classify all of

our patients, although a lot of them were classified in

syndromes that were not clearly defined. This applies pri-

marily to the patients with cryptogenic etiology that could

not fit in one of the clinically described cryptogenic epi-

lepsies. Cryptogenic was used to denote epilepsy in which

there was no identifiable underlying etiology and the form

of epilepsy was not one of the idiopathic syndromes. Fur-

thermore, ‘‘other primary generalized syndromes’’ were not

clearly defined either. If a patient had exclusively grand

mal seizures and the seizures occurred without any relation

to circadian rhythm, and the criteria for idiopathic gen-

eralized epilepsy were met including generalized EEG

discharges, the patient was classified as ‘‘other primary

generalized epilepsies not defined above’’.

In our study 45.3% of all patients were classified as

idiopathic generalized epilepsies. Despite the relatively

clear diagnostic criteria, the proportion of IGE syndromes

has varied considerably in different surveys of childhood

epilepsy, ranging from 1.7% in Japan [19] to 42.2% in the

Acta Neurol Belg (2012) 112:147–154 149

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150 Acta Neurol Belg (2012) 112:147–154

123

Netherlands [20]. The great proportion of patients with

idiopathic etiology in our study reflects the patient popu-

lation—neurologically normal adolescents with no initially

associated neurological impairment or mental retardation.

Another possible explanation for the great proportion of

idiopathic epilepsy is that a few patients with extremely

rapid secondary generalization of seizures, in whom it was

clinically impossible to detect focal onset and with no focal

Table 2 Seizure control in relation to etiology and epilepsy syndrome

Seizure control Good Partial Poor Total

N (%) 59 (57.3) 25 (24.3) 19 (18.4) 103 (100)

Etiology

Idiopathic 40 (71.4) 8 (14.3) 8 (14.3) 56 (100)

Childhood absence epilepsy 4 (100) 0 0 4 (100)

Juvenile absence epilepsy 5 (71.4) 2 (28.6) 0 7 (100)

Juvenile myoclonic epilepsy 8 (66.7) 1 (8.3) 3 (25) 12 (100)

Epilepsy with grand mal seizures on awakening 14 (73.7) 3 (15.8) 2 (10.5) 19 (100)

Other generalized idiopathic epilepsy 9 (64.3) 2 (10.5) 3 (21.4) 14 (100)

Cryptogenic 10 (41.7) 9 (37.5) 5 (20.8) 24 (100)

Symptomatic 8 (34.8) 10 (43.5) 5 (21.7) 23 (100)

Cortical dysplasia 3 (50) 0 3 (50) 6 (100)

MTLE with HS 2 (66.7) 1 (33.3) 0 3 (100)

Nodular heterotopia 1 (100) 0 0 1 (100)

Cortical atrophy 0 1 (100) 0 1 (100)

Post-infectious 0 3 (100) 0 3 (100)

Cerebrovascular disease 0 1 (33.3) 2 (66.7) 3 (100)

Cysts and gliosis 2 (40) 3 (60) 0 5 (100)

Tumor 0 1 (100) 0 1 (100)

MTLE with HS mesial temporal lobe epilepsy with hippocampal sclerosis

Table 3 Differences in gender, age, years of epilepsy, control of epilepsy and use of AED between idiopathic, cryptogenic, and symptomatic

subgroups

N (%) Idiopathic Cryptogenic Symptomatic Total Chi square p value

Gender

Male 21 (53.9) 7 (17.9) 11 (28.2) 39 (100) v2 = 1.745 p = 0.418

Female 35 (54.7) 17 (26.6) 12 (18.7) 64 (100)

Duration of epilepsy in years

\1 7 (43.7) 6 (37.5) 3 (18.8) 16 (100) v2 = 7.001 p = 0.537

1–2 13 (52) 7 (28) 5 (20) 25 (100)

3–5 21 (63.7) 4 (12.1) 8 (24.2) 33 (100)

6–9 13 (59.1) 5 (22.7) 4 (18.2) 22 (100)

[10 2 (28.6) 2 (28.6) 3 (42.8) 7 (100)

Seizure control

Good 40 (67.8) 10 (16.9) 9 (15.3) 59 (100) v2 = 10.707 p = 0.030

Partial 8 (32) 9 (36) 8 (32) 25 (100)

Poor 8 (42.1) 5 (26.3) 6 (31.6) 19 (100)

AED

Conventional 46 (55.4) 21 (25.3) 16 83 (100) v2 = 2.605 p = 0.272

New 10 (50) 3 (15) 7 (35) 20 (100)

AED

Monotherapy 54 (60%) 21 (23.3) 15 (16.7) 90 (100) v2 = 14.402 p = 0.001

Polytherapy 2 (15.4) 3 (23.1) 8 (61.5) 13 (100)

Acta Neurol Belg (2012) 112:147–154 151

123

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152 Acta Neurol Belg (2012) 112:147–154

123

discharges on EEG, might have been misdiagnosed as

having the syndrome of general tonic–clonic seizures on

awakening or ‘‘other primary generalized epilepsy’’.

Among the idiopathic subgroup, JME were diagnosed in

21.4% of cases, which also reflects the age of the study

population. In epidemiological surveys the prevalence of

JME varies from 3.1 to 11.9% [21]. These results show a

clear association between the age ranges of the study group

and the prevalence of this age-related syndrome. In studies

concerning childhood and adolescence the figures are much

higher than in studies including all ages. In studies among

patients with IGEs, 20–27% have been diagnosed with

JME [21, 22], which is in agreement with our results

(21.4%).

Dominant seizure types in our sample were primary

generalized TCS (40.8%) followed by partial seizures with

secondary generalization (19.4%). This seizure profile

appears to be similar to other studies of adolescents. The

prevalence of partial seizures, in children, has been

reported to be higher than that of generalized seizures [16],

or equally frequent. We can conclude that the prevalence of

partial seizures in studies of children may be attributed to

the high frequency of benign epilepsy with centrotemporal

spikes (BECTs). However, there were no BECT patients

observed in our sample. One of the reasons for this is most

probably the very fact that the observed sample group

included adolescents, aged 12–22; at that age the patients

with BECT are mostly undergoing spontaneous remissions.

Our study suggests that the treatment of adolescents

with epilepsy was not optimal. More than 40% of adoles-

cents reported seizures during the previous 12 months,

suggesting that treatment was less effective in comparison

with similar studies of adult or child populations [23–26]. It

is well known that the remission rate depends on the eti-

ology of the seizures. In several long-term prospective

studies, Sillanpaa et al. [26, 27] found 5-year terminal rates

for idiopathic, cryptogenic, and remote symptomatic sei-

zures to be 95, 68, and 45%, respectively. In a study

including children and adults Annegers et al. [28] found the

remission rate of 42% after follow-up of 1 year. In our

study a complete seizure control for 1 year was achieved in

71.4% of patients from the idiopathic group, 41.7% from

the cryptogenic, and 37.5% from the symptomatic group.

In our sample, valproate was the most commonly used

antiepileptic drug in monotherapy as well as in poly-

therapy. Patients treated with a combination of AEDs often

have a poorer epilepsy control compared with those on

monotherapy, which is also in accordance with our study.

We found that traditional AEDs strongly dominated treat-

ment. The oldest drug, phenobarbital, had a limited use in

only one patient in this population, but it is still used in our

hospital in the ‘‘older’’ patient groups. New AEDs, topi-

ramate, and lamotrigine, the only drugs available free of

charge at the national market were primarily used as

add-on therapy, which is in accordance with the recom-

mendations of the Serbian Medical Product Agency. New

AEDs are exceptionally approved by the agency to be used

as monotherapy only in special patient populations (women

of child-bearing potential or adverse effects of conven-

tional AEDs).

One of the reasons for the less optimal treatment could

be the fact that new AEDs are underused and many other

new AEDs are still not available in our country. Brodie

and French [29] have suggested that a wider use of new

AEDs can improve the situation for many epilepsy

patients. Several studies have also demonstrated that new

drugs are equally effective as the older ones and that

several of the new drugs have a better side-effect profile

and a lower risk of interaction [5, 7, 8, 30]. Our study

shows a low utilization of new AEDs and we can con-

clude that therapeutic possibilities were not fully exploi-

ted. The reason could be unsatisfactory health care

service. A better understanding of the economic aspects

should lead to further improvements in epilepsy care by

targeting limited resources in the most beneficial way for

the patients [31].

Another reason for the less optimal treatment can be that

adolescents have a poorer compliance than other age

groups. A number of studies have demonstrated that

approximately 50% of adolescents with long-term condi-

tions fail to comply with their treatment recommendations

[1, 2, 32–34]. On the other hand, it is a common belief that

adolescents with epilepsy show good compliance with their

medication since the neglect of medical treatment may

cause epileptic seizures. Good motivation, a strong sense of

normality, support from parents and physicians, a positive

attitude towards the disorder and treatment, as well as no

fear of seizures lead to good compliance. All of these

factors should be considered and implemented in the care

of adolescents with epilepsy.

Conclusion

Many adolescents with uncomplicated epilepsy have sei-

zures despite antiepileptic treatment. Poor compliance,

insufficient use of new AEDs, and unsatisfactory health-

care systems, insufficiently targeting special needs, and

problems related to adolescence are the possible reasons

for suboptimal treatment at tertiary epilepsy centers in the

twenty-first century.

Acknowledgments This study was supported by the Serbian Min-

istry of Education and Science, Grant Number 175006/2011. The

study was approved by the local Ethics Committees.

Conflict of interest None.

Acta Neurol Belg (2012) 112:147–154 153

123

References

1. Kyngas H (2000) Compliance with health regimens of adoles-

cents with epilepsy. Seizure 9:598–604

2. Besag FMC (1996) Modern management of epilepsy: adoles-

cents. Baillieres Clin Neurol 5:803–820

3. Perucca E (1996) Principles of drug treatment. In: Shorvon S,

Dreifus F, Fish D, Thomas D (eds) The treatment of epilepsy.

Blackwell Science, Oxford

4. Shorvon S (1997) Antiepileptic drug monotherapy versus poly-

therapy: economic aspects. Epilepsia 38:S17–S20

5. French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T

et al (2004) Efficacy and tolerability of the new antiepileptic

drugs. I. Treatment of new-onset epilepsy: report of the TTA and

QSS Subcommittees of the American Academy of Neurology and

the American Epilepsy Society. Epilepsia 45:401–409

6. French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T

et al (2004) Efficacy and tolerability of the new antiepileptic

drugs. II. Treatment of refractory epilepsy: report of the TTA and

QSS Subcommittees of the American Academy of Neurology and

the American Epilepsy Society. Epilepsia 45:410–423

7. Perucca E (2005) An introduction to antiepileptic drugs. Epi-

lepsia 4:31–37

8. Schmidt D, Elger CE (2004) What is the evidence that

oxcarbazepine and carbamazepine are distinctively different

antiepileptic drugs? Epilepsy Behav 5:627–635

9. Boon P (2008) Impact of reimbursement restrictions on the

choice of antiepileptic drugs: Belgian Study on Epilepsy Treat-

ment (BESET). Seizure 17:350–357

10. Commission on Classification and Terminology of the Interna-

tional League against Epilepsy (1989) Proposal for revised

classification of epilepsies and epileptic syndromes. Epilepsia

30:389–399

11. Cramer JA, Westbrook LE, Devinsky O, Perrine K, Glassman MB

et al (1999) Development of the quality of epilepsy inventory for

adolescents: the QOLIE-AD-48. Epilepsia 40:1114–1121

12. Cowan LD, Bodensteiner JB, Leviton A, Doherty L (1989)

Prevalence of the epilepsies in children and adolescents. Epi-

lepsia 30:94–106

13. Joensen P (1986) Prevalence, incidence, and classification of

epilepsy in the Faroes. Acta Neurol Scand 74:150–155

14. Rwiza HT, Kilonzo GP, Haule J, Matuja WB, Mteza I et al

(1992) Prevalence and incidence of epilepsy in Ulanga, a rural

Tanzanian district: a community-based study. Epilepsia 33:

1051–1056

15. Giuliani G, Terziani S, Senigaglia AR, Luccioni G, Foschi N et al

(1992) Epilepsy in an Italian community as assessed by a survey

for prescriptions of antiepileptic drugs: epidemiology and pat-

terns of care. Acta Neurol Scand 85:23–31

16. Sidenvall R, Forsgren L, Heijbel J (1996) Prevalence and char-

acteristics of epilepsy in children in Northern Sweden. Seizure

5:139–146

17. Hauser WA, Annegers JF, Kurland LT (1991) Prevalence of

epilepsy in Rochester, Minnesota: 1940–1980. Epilepsia 32:

429–445

18. Mullins GM, O’Sullivan SS, Neligan A, McCarthy A, McNamara B

et al (2007) A study of idiopathic generalized epilepsy in an Irish

population. Seizure 16:204–210

19. Oka E, Ishida S, Ohtsuka Y, Ohtahara S (1995) Neuroepidemi-

ological study of childhood epilepsy by application of interna-

tional classification of epilepsies and epileptic syndromes (ILAE

1989). Epilepsia 36:658–661

20. Callenbach PM, Geerts AT, Arts WF et al (1998) Familial

occurrence of epilepsy in children with newly diagnosed multiple

seizures: Dutch study of epilepsy in childhood. Epilepsia 39:

331–336

21. Thomas P, Genton P, Geliesse P, Wolf P (2002) Juvenile myo-

clonic epilepsy. In: Roger J, Bureau M, Dravet C et al (eds)

Epileptic syndromes in infancy, childhood and adolescence, 3rd

edn. John Libbey, London

22. Genton P, Gelisse P, Thomas P (2000) Juvenile myoclonic epi-

lepsy today: current definitions and limits. In: Schmitz B, Sander

T (eds) Juvenile myoclonic epilepsy: the Janz syndrome.

Wrightson Biomedical Publishing, Petersfield

23. Camfield PR, Camfield CS (2000) Treatment of children with

‘‘ordinary’’ epilepsy. Epileptic Disord 2:45–51

24. Eriksson KJ, Koivikko MJ (1997) Prevalence, classification and

severity of epilepsy and epileptic syndromes in children. Epi-

lepsia 38:1275–1282

25. Cockerell OC, Johnson AL, Sander JW, Shorvon SD (1997)

Prognosis of epilepsy: a review and further analyses of the first

nine years of the British National General Practice Study of

Epilepsy, a prospective population-based study. Epilepsia 38:

31–46

26. Sillanpaa M, Jalava M, Kaleva O, Shinnar S (1998) Long-term

prognosis of seizures with onset in childhood. N Engl J Med

338:1715–1722

27. Sillanpaa M (2000) Long term outcome of epilepsy. Epileptic

Disord 2:79–88

28. Annegers JF, Hauser WA, Elveback LR (1979) Remission of

seizures and relapses in patient with epilepsy. Epilepsia 20:

729–737

29. Brodie MJ, French JA (2000) Management of epilepsy in ado-

lescents and adults. Lancet 22:323–329

30. Landmark CJ, Ryter E, Johannessen SI (2007) Clinical use of

antiepileptic drugs at a referral centre for epilepsy. Seizure

16:356–364

31. Pachlatko C (1999) The relevance of health economics to epi-

lepsy care. Epilepsia 40:S3–S7

32. Michaud PA, Frappier JY, Pless IB (1991) Compliance in ado-

lescents with chronic disease. Arthritis Care Res 8:329–336

33. Adams S, Pill R, Jones A (1997) Medication, chronic illness and

identity: the perspective of people with asthma. Soc Sci Med

45:189–201

34. Kyngas H, Hentinen M, Koivukangs P, Ohinmaa A (1996) Young

diabetics’ compliance in the framework of the MIMC model.

J Adv Nurs 24:997–1005

154 Acta Neurol Belg (2012) 112:147–154

123