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Juli September 2006 Vol. 25, No.3
Number of pre-treatment seizure as
prognostic factor of convylsive epilepsy
in childhood and young adult onset
Efek hipoglikemik daging buah
ma h kota dewa (Phaleria Macrocarpa
(Scheff.) Boerl.) terhadap kadar gula
darah pada manusia sehat setelah
pembebanan glukosa
Pengaruh olahraga aerobik terhadap
kadar estradiol pada wanita
pascamenopause : studi randomsasi
selama 12 minggu
The relationship between maternal blooc
zinc level and the size of newborn baby
Diagnosis dan penatalaksanaan
hand-arm vibration syndrome pada
pekerja pengguna alat yang bergetar
Nutrition and .immune system in the
elderly
Universa Medicina
Jurnal Kedokteran Trisakti
DAFTAR IS1
Halaman
Editorial : Psychosomatic medicine, past and future..
A. Prayitno
...............................................
Tips of Today
Life-threatening malfunction of implantable cardiac devices................................
Number of pre-treatment seizure as prognostic factor of convulsive epilepsy in
childhood and young adult onset.. ........................................................................
Rizaldy Pinzon, Harsono, Imam Rusdi
i
...
111
105
Efek hipoglikemik daging buah mahkota dewa (PhaleriaMacrocarpa (Scheff.) Boerl.)
terhadap kadar gula darah pada manusia sehat setelah pembebanan glukosa.. ............. 114.
Meiyanti, Hedi R. Dewoto, Fransiscus D. Suyatna
Pengaruh olahraga aerobik terhadap kadar estradiol pada wanita pascamenopause:
studi randomisasi selama 12 minggu.. ............................................................ 121
Martiem Mawi, Reza Tandean, Jemmy Hermawan, MR. Rachmawati,
Lie T. Merijanti, Nugroho Abikusno
fie relationship between maternal blood zinc level and the size of newborn baby.. ...... 127
Widagdo, Harmon Mawardi, Firda Fairuza, Meiharty B. ZulkiJli,
Tjahaya Bangun, Augustine Matatula, Slamet Zaeny
Diagnosis dm penatalaksanaan hand-arm vibration syndrome pada pekej a pengguna
alat yang bergetar.. ................................................................................... 133
Diana Sarnara
Nutrition and immune system in the elderly.. .................................................... 140
R i m K, Kusumaratna
Number of pre-treatment seizure as prognostic factor of
convulsive epilepsy in childhood and young adult onset
Rizaldy Pinzon", Harsono**, dan Imam Rusdi**
'Neurology Department, Dr. Haulussy District ~ o s ~ i t~aml b o n
"Neurology Department, Gadjah Mada University School of Medicine
ABSTRACT
Epilepsy is one of the most common neurological disorders with complex problem. The role of number of pretreatment seizure is not conclusive yet. A historical cohort design was conducted to evaluate the role of number ofpretreatment seizure as predictive factor of remission. The subjects were epilepsy patients with onset 2-25 years old with
convulsive seizure manfestation that at least had taken medication for 2 years. This study included 110 epilepsy
patients, consisted of 42.7% male and 57.3%female. Six months remission with 2 years medication were achieved in
86patients (78.2%). The sign $cant predictive factors for not achieving 6 months remission are seizure type, number
ofpre treatment seizure, and the presence of neurological dejcit. Twelve months remission were on[y achieved by 48
patients (43.6%). The sign$cant predictive factors for not achieving 12 months remission were high number ofpretreatment seizure, the presence of neurological dejcit, and the incompliance of treatment program. The average
numbers of breakthrough seizure were sign$cant[y higher in patients with high number of pre treatment seizure,
presence of neurological dejcit, partial type of epilepsy, and non-compliancepatients. Most epilepsy patient achieved
6 months remission with treatment, but on[y about hayof them achieved 12 months remission. High number of pre
treatment seizure was sign $cant poor predictive factors for achieving remission. The strongest poor prognostic
factors were the presence of neurological deficit.
Keywords: Epilep~y,childhood, young adult, pre treatment seizure
Jumlah bangkitan sebelum terapi rutin obat anti epilepsi sebagai
faktor prognosis epilepsi masa anak-anak dan dewasa muda
ABSTRAK
Epilepsi merupakan salah satu penyakit neurologi utama dengan masalah yang kompleks. Peran jumlah bangkitan
sebelum terapi rutin sebagai faktor prognosis sampai saat ini masih kontroversial. Sebuah rancangan kohort historikal
digunakan untuk menilai peran jumlah bangkitan sebelum terapi sebagai salah satu faktor prediktor remisi epilepsi.
Subyek penelitian adalah pasien epilepsi dengan onset pada usia 2-25 tahun, yang telah mendapat terapi minimal
selama 2 tahun. Hasil penelitian diperoleh dari 110 pasien epilepsi, terdiri dari 42,794 laki-laki dan 57,3% perempuan.
Remisi minimal 6 bulan dengan terapi 2 tahun tercapai pada 86 pasien (78,2%). Faktor prediktor tercapainya remisi
adalah tipe bangkitan, jumlah bangkitan sebelum terapi, dan ada tidaknya defisit neurologi penyerta. Remisi 12 bulan
tercapai pada 48 pasien (43,696). Faktor prediktor remisi yang penting adalah jumlah bangkitan sebelum terapi,
adanya defisit neurologi, dan kepatuhan terhadap program terapi. Jumlah bangkitan dalam program terapi secara
signifikan lebih tinggi pada kelompok dengan jumlah bangkitan sebelum terapi yang tinggi, pasien dengan defisit
neurologi, tipe epilepsi yang parsial, dan pasien yang tidak patuh. Sebagian besar pasien epilepsi dapat mencapai
remisi 6 bulan, namun hanya kurang lebih separuh pasien yang mencapai remisi 12 bulan. Jumlah bangkitan yang
tinggi sebelum terapi merupakan faktor prediktor buruk tercapainya remisi. Faktor prediktor yang paling bermalaa
untuk tidak tercapainya remisi adalah adanya defisit neurologi yang menyertai epilepsi.
Kata kunci: Epilepsi, anak-anak, dewasa muda, jumlah bangkitan sebelum terapi
Korespondensi : "Rizaldy Pinzon
Neurology Department
Dr M Haulussy District Hospital Ambon
Elnail : [email protected]
B'nzon, Warsono, %us&
INTRODUCTION
Prognostic factor of convuljive epihpsy
in childhood and young adult onset of convulsive
seizure.
Epilepsy is o n e o f t h e most common
neurological disorder with complex additional METHODS
problems.(')Epilepsy patients have greater
probability for being injured, death, social Research design
stigma, fear, anxiety, cognitive disturbance, and
Historical cohort design was used in this
psychiatric disorder.t2)Theestimated number of study. This design was used to follow up the
epilepsy patients worldwide in 2000 are 50 cohort that had been established in the past. A
million patients, 37 million patients among them good quality secondary data was needed to
are primary type, and 80% lives in developing support the historical cohort study.('*)
countries.(')Epilepsy is a chronic disorder that
commonly cause medical and quality of life Subjects
problem among the sufferer.(3)Epilepsy affect
The subjects of this study were childhood
the patients, the family, and the neighb~rhood.(~)and young adults onset with convulsive epilepsy
Adequate information should be given to the that have taken medication for at least 2 years.
patients and their family. Adequate information The point to start t h e follow up was the
is very important for enhancing the compliance beginning of medication administration. The
inclusion criteria were: (i) childhood and young
of therapeutic p r ~ g r a m . ' ~ , ~ )
The main concept of prognosis in epilepsy adult onset epilepsy (2-25 years old), (ii)
is the chance for achieving remission and convulsive type of seizure, (iii) had been taken
probability of premature death.(') The other medication for minimally 2 years, (iv) obtained
p r o g n o s t i c c o n c e p t s a r e q u a l i t y o f life, clinical service for the epilepsy in Sardjito
psychosocial status, the neurological function, General Hospital, (v) accompanied with parents
and ability for formal edu~ation.(~)Recurrent
and or relative at hospital visit, and (vi) had
prolonged seizure are believed for causing brain completed medical record. The exclusion criteria
damage. Epilepsy is also thought to be a are (i) subject who refused to join the study, and
progressive disease. The brain damage is caused (ii) the patients and the family were not sure
by prolonged exposure to the excitatory amino about the number of pre treatment seizure.
acid (particularly gl~tamate).'~)
The development
of new epileptic focus in recurrent and prolonged Clinical variable
seizure are believed to be facilitated phenomenon
The measurement of prognostic factors
(kindling model of epilepsy). Primary epileptic performed for each clinical variable, number of
focus can induce the surrounding brain area, and pre-treatment seizure, and compliance of
c a u s e s a b n o r m a l paroxysmal electrical treatment program. T h e clinical a n d
activity.('O)The recurrent electrical stimulation demographic factors that were measured were
also causes increasing brain sensitivity and sex, age, type of epilepsy, the origin of epilepsy,
permanent declining of seizure threshold.(") the presence of neurological deficit, and EEG
Previous studies showed that the role of number profile. Patients were classified into 2 main
of pre-treatment seizure as prognostic factors groups based on the number of pre-treatment
is still controversial.
seizure, namely high number of pre-treatment
The aim of this study is to measure the role seizure when the seizure exceeded 10 times
of pre-treatment seizure as prognostic factors before treatment.
Outcome
The primary outcome is minimally 6
months c o n t i n u o u s remission in 2 years
treatment. The secondary outcome is 12 months
continuous remission and average of months
with positive breakthrough seizure. The use of
6 months remission is based on the review of
Carpay, et al.(I3)which showed that 2 6 months
was a profile of good remission. Patients that
achieved 6 months continuous remission had
great probability of achieving full remission.
Statistical analysis
The probability for achieving remission
was described with relative risk, the precision
o f m e a s u r e m e n t w a s s h o w n with 9 5 %
confidence interval. The presence of
confounding factors were controlled by multiple
logistic regression analysis. The survival
analysis with Kaplan-Meier method use to
describe the probability for achieving remission
in particular time. The statistical package
programs used in this study were SPSS 10.0
and Epi Info 6.0.
RESULTS
Patients characteristic
The data were obtained from 110 patients
with convulsive epilepsy, consist of 47 (42.7%)
male and 63 (57.3%) female. The characteristic
of the patients were showed in Table 1.
More than 30% patients took their routine
medication after more than ten convulsive
seizure, and only 18.2% cases had been treated
after their first seizure. Among the group that
had been treated after their first seizure, most
of them had general tonic clonic seizure. In
contrast, of 11 patients with partial complex
seizure. 81.8% were treated after > I 0 times
s e i z u r e . T a b l e 2 s h o w e d n u m b e r o f pre
treatment seizure among the subjects.
Table 1. Characteristic of patients
Characteristic
Sex
male
female
Age at onset
.
<5 years old
5-12 years old
> 12 years old
Type of convulsive seizure
general
partial
idiopathic epilepsy
symptomatic epilepsy
Number of pre treatment
seizure
510
> 10
EEG recording
normal
abnormal
no data
The history of febrile seizure
present
absent
Family history of epilepsy
present
absence
History of status epilepticu
present
absence t
Neurological deficit
present
absence t
N
Percentage
47
63
42.7%
57.3%
32
38
40
29.1%
34.5%
36.4%
88
22
65
45
80%
20%
59.1%
40.9%
73
37
66.4%
33.6%
17
81
12
15.5%
73.6%
10.9%
31
79
28.2%
71.9%
13
97
11 3 %
88.2%
12
98
10.9%
89.1%
17
93
15.5%
84.5%
Table 2. Number of pre treatment convulsive
seizure among the study subjects
Number of pre
treatment seizure
N
Percentage
1 times
2 times
3-5 times
6- 10 times
> 10 times
20
21
20
12
37
18.2%
19.1%
18.2%
10.9%
33.6%
fi'nzon, 3ianon0, Rmd?
&ognostic factor of convuhive epilepsy
Table 3. The significant predictive factors for 6 months remission
Characteristic
Type of seizure
General tonic clonic
Simple partial
Complex partial
Number of pre-treatment seizure
5 10
> 10
Neurological deficit
Absence
Presence
*RR
=
Proportion of six
months remission
RR* (95% CI)
P
81.8%
81.8%
45.5%
l .OO (0.74 - 1.34)
0.56 (0.29 - 0.87)
0.68
0.013'
84.9%
64.9%
0.76 (0.59 - 0.98)
0.016'
82.8%
52.9%
0.63 (0.405 - 0.92)
0.006.
relative risk
Six months remission
Six months remission during treatment was
achieved in 86 patients (78.2%). Table 3 showed
the significant predictive factors for achieving
6 months remission. Table 3 showed that
complex partial seizure, high number of pretreatment s e i z u r e , and the presence of
neurological deficit were significantly poor
predictive factors for achieving 6 months
remission. Sex, age of onset, origin of epilepsy,
history of febrile seizure, history of status
epilepticus, family history of epilepsy,
compliance of therapeutic program, and, EEG
pattern were not significant predictive factors.
Twelve months remission
The 12 months remission during treatment
was achieved in 4 8 (43.6%) patients. Table 4
showed the significant prognostic factors for
achieving 12 months remission.
Table 4 showed that significant predictive
factors for 12 months remission were number
of pre treatment seizure, c o morbidity of
neurological deficit, and compliance of treatment
program. None of the patients with complex
partial seizure achieved 1 2 months remission
Table 4. The significant predictive factors for 1 2 months remission
Characteristic
Proportion of 12
months remission
RR* (95% CI)
P
50.7%
29.7%
0.587 (0.34-0.92)
0.036'
49.5%
1 1.8%
0.238 (0.06-0.889)
0.004.
5 1.4%
30.0%
0.583 (0.345-0.986)
0.029.
50%
36.4%
0%
0.73 (0.32-1.63)
NA
0.039
Number of pre-treatment seizure
5 10
> 10
Neurological deficit
Absence
Presence
Compliance of treatment
Compliance
Incompliance
Type of seizure
General tonic clonic
Simple partial
Complex partial
* RR = relative risk: NA=
not available
Table 5. Average of months with positive breakthrough seizure in
the first year of anti epileptic treatment
Characteristic
Mean rt SD
P
Type of seizure
General tonic clonic
Simple partial
Complex partial
Number of pre-treatment seizure
2.81 k 2.78
3.45 k 3.59
6.64 k 3.29
0.00 1'
2.86 k 2.60
4.03 =t3.29
0.0 16'
2 10
> 10
Neurological deficit
Presence
Absence
Compliance of treatment
Compliance
Non compliance
4.94 k 2.82
2.95 =t3.06
0.014'
2.76 k 3.03
4.13 k 3.07
Breakthrough seizure
Breakthrough seizure was defined a s
number of month with positive seizure during
an anti-epileptic treatment. The average number
of breakthrough seizure was significantly higher
in patients with partial type of epilepsy, high
number pre-treatment seizure, incompliance, and
the presence of neurological deficit (Table 5).
0.026'
N u m b e r o f pre-treatment seizure a n d the
probability for achieving remission
The proportion of six months remissions
were lower in patients with high number of pretreatment seizure. Similar result was shown in
12 months remission. (Table 6 and Table 7).
Table 6. The trends of 6 months remission rate in patients with number of pre-treatment seizure
Number of pre-treatment
seizure
1 times
2 times
3-5 times
6- 10 times
> 10 times
Six months remission
Yes
No
20 (100%)
0 (0%)
17(81%j
4 ( I9%)
18 (90%)
2 (1 0%)
7 (58.3%)
5 (4 1.7%)
24 (64.8%)
13 (35.2%)
p (chi square
for trend)
0.0 14
Table 7. The trends of 12 months remission rate in patients with number of pre-treatment seizure
Number of pre-treatment
seizure
1 times
2 times
3-5 'times
6-10 times
> 10 times
Twelve months remission
Yes
No
13 (65%)
12 (57.1%)
7 (35%)
5 (4 1.7%)
10 (27%)
7 (35%)
9 (42.9%)
13 (65%)
7 (58.3%)
27 (73%)
p (chi square
for trend)
0.0079
Prognosticfactor of convuhive epilepsy
Bnzon, Xatsono, msd?
1.2
1 0 -
8.
.6
-
-
No of seizure
I
4.
2
<I= 10
r
-
+
I
,,,r
-
J
,
r: > 10
,J
00.
C-,,,,,d
+
-2
0
2
a,
8
6
10
12
14
Time of remission (months)
Figure 1. The probability of achieving 6 months remission during first year therapy based on
the status of pre-treatment seizure
Patients with high number of pre-treatment
seizure also had significantly lower probability
for achieving 6 months remission during the
first Year of treatment (Figure 1).
Table 8. The multiple logistic regression for not achieving 6 months remission during treatment
Prognostic factors
High number of pre-treatment seizure
Complex partial seizure
The presence of neuroloaical deficit
B
1.104
1.323
1.440
SE
0.493
1.036
0.578
Exp (B) I OR*
3.017
3.755
4.220
95% CI
1.149 - 7.924
0.811-13.903
1.359 - 13.101
P
0.025'
0.202
0.013*
*OR = odds ratio
Table 9. The multiple logistic regression analysis for not achieving 12 months
remission during treatment
Prognostic factors
B
SE
Exp (B) I OR*
95% CI
The presence of neurological deficit
partial type of epilepsy High number of pre-treatment seizure
Non compliance of treatment program
*OR = odds ratio
2.086
1.440
0.548
1.071
0.817
0.639
0.465
0.475
8.056
4.222
1.730
2.917
1.623 - 39.975
1.207 - 14.766
0.682 - 4.387
1.173 - 7.257
P
0.01 1'
0.024~
0.248
0.02 I *
Multiple logistic regression analysis
Table 8 and 9 showed the significant
predictive factors of remission i n multiple
logistic regression analysis.
The multiple logistic regression analysis
showed that high number of pre-treatment
seizure and the presence of neurological deficit
were the poor prognostic factors for achieving
6 months remission.
The presence of neurological deficit,
partial type of epilepsy, and non compliance of
treatment program were the poor prognostic
factors for achieving 12 months remission.
aspartate (NMDA) receptor and excitatory
input, (ii) the loss of inhibition, and (iii)
neuronal reorganization.'") The experimental
study showed that recurrent seizure inhibit cell
multiplication, inhibited myelin accumulation,
and d i s r u p t e d i n t e r cell connection.(18)
Glutamate is a very important factor o f
neuronal damage, the neuronal damage is
primarily mediated by excessive glutamate
release, and not because of hypoxic theory.(I9)
lThe most vulnerable area of secondary
damage through recurrent and prolonged
seizure is limbic system. The sprouting and
permanent reorganization is primary noted in
DISCUSSION
mossy fibers synaptic c o n n e ~ t i o n . ( ' ~ There
.*~)
are 3 hypothesis of the role of mossy fibers: (i)
This study showed that high number of t h e damage o f mossy f i b e r s will induce
pre-treatment seizure was one of the prognostic sprouting and induce subsequent seizure, (ii)
factors in convulsive epilepsy. The role of the damage of mossy fibers will cause hypo
number of pre-treatment seizure was based on activity of inhibition function, and (iii) the
the theory that prolonged and recurrent seizure survive mossy fibers will change in nature, and
caused neuronal damage and development of very excitable and cause sub sequent seizure.(Ig)
new epileptic foci. The neuronal damage is
Based on the kindling theory, Reynolds(20)
mediated by excessive excitatory of amino suggested that anti epileptic drug must be
aCid.(10.11.14)
prescribed soon for preventing structural
S e i z u r e induced s u b s e q u e n t s e i z u r e change due to epilepsy. The prevention of
through facilitation phenomenon. This concept development of secondary epileptic foci can
known as kindling model of epilepsy. Electrical also be performed by optimal control of seizure.
abnormality from primary focus can induce the Poor medication program and seizure control
surrounding area and develop paroxysmal will cause chronic and refractory epilepsy.(I6)
e l e c t r i c a l a b n o r m a l i t y . ( l O 'T h e p r e v i o u s
The result of previous studies were still
experimental study showed that the neuronal
inconsistent. The prospective study of 479c h a n g e s s u r r o u n d i n g t h e f o c u s w e r e childhood onset epilepsy showed that patients
permanent.(IS)Thekindling phenomenon also who exceeded 10 times of pre-treatment seizure
observed in experimental s u b convulsive have lower probability of remission rate. The
s t i m u l a t i o n . T h e s e n s i t i v i t y o f neuron risk of breakthrough seizure is significantly
increased, and there will be permanent declining lower in patients with low number of preof seizure threshold.(g)
treatment seizure ( < l o ) (15% vs 52%, RR=
T h e process of developing secondary 0.28, p<0.001).(2') Other prospective study
epileptic foci also mediated by long term showed that the risk of refractory epilepsy was
potentiation mechanism and mirror effect.(I6) significantly higher in patients with > 20 times
The steps of development of secondary epileptic pre-treatment seizure (5 1% vs 29%, RR= 1.8,
foci were: (i) stimulation o f N-methyl d- p<0.00
There were significant linear trend
Prognosticfactor of convulsive epihpsy
finzon,Hanono, Kush
that high number of pre-treatment seizure was
associated with probability of refractory.
Other studies did not confirm the role of
pre-treatment seizure as prognostic factors.
)
Community based study by C o ~ k e r e l l (in~ ~792
epilepsy patients showed that high number of
pre-treatment seizure was not associated with
poor prognostic factors for 5-year remission.
Prospective study in 446 childhood onset
epilepsy showed that there was no significant
risk difference for achieving remission i n
patients with low (<25) and high number of pretreatment seizure ( R R = l . 17, 95% CI=0.791 .76).(24)
The clinical implications of this study are
that seizure must be recognized soon, and
optimal treatment is needed for preventing
chronic and intractable epilepsy. Early optimal
treatment is also needed for preventing injury,
premature death, cognitive impairment, and
psychosocial ~ t i g m a . ( ~ ~A. ' ~randomized
)
controlled trial compared the risk of recurrent
seizure between patients with early therapy (soon
after first seizure) and patients with late therapy
(after recurrent seizure). The result showed that
risk of recurrence in two year period was higher
in patients with late therapy (RR= 2.8,95% CI=
1.9-4.2).(") Study by Gilad, et a1.(28)in 87
general tonic clonic epilepsy showed that
probability of seizure free was significantly
higher (p<O.Ol) in patients with early treatment
program.
The other significant predictive factors of
remission are type of epilepsy, compliance of
treatment, and neurological deficit. Partial type
of epilepsy, particularly complex partial seizure
is associated with poor prognosis.(29)This study
failed to show that symptomatic epilepsy had
worse prognosis than idiopathic epilepsy. The
most reasonable reason was an inadequate
diagnosis of symptomatic epilepsy in this study.
In most cases diagnosis was only based on
history. In childhood onset of epilepsy the good
prognostic factors are: ( i ) the absence o f
neurological deficit, (ii) normal psychomotor
function, (iii) normal IQ, (iv).age of onset > 2
years old, (v) low number of pre-treatment
seizure, (vi) normal EEG recording, and (vii)
early response to treatment.c30)
The compliance of treatment program is
also an important factor. Simple and single
treatment r e g i m e n t w i l l i m p r o v e t h e
compliance.(3')A d e q u a t e c o u n s e l i n g a n d
information about long treatment program and
the importance of regular medication also
enhance the compliance.(32)There are four main
factors that enhancing the treatment compliance:
(i) support form the physicians, (ii) support form
the family, (iii) positive prospective of epilepsy,
and (iv) high motivation.(33)
CONCLUSIONS
Most epilepsy patients achieved 6 months
remission with treatment, but only about half of
them achieved 12 months remission. High
number of pre treatment seizure was one of the
significant poor predictive factors for achieving
remission. The other prognostic factors were
type of epilepsy, incompliance of treatment
program, and the presence of neurological
deficit. The strongest poor prognostic factors
were the presence of neurological deficit.
References
1.
2.
3.
4.
World Health Report. Epilepsy in the world health
report, mental health: new understanding, new
hope. Geneva: World Health Organization; 2001.
Shafer PO. Improving the quality of life in epilepsy:
non medical issues too often overlooked. Postgrad
Med Online 2002; 1 1 1: 1.
Mills N, Bachmann M, Harvey I, McGrowen M,
Hine 1. Patient's experience of epilepsy and health
care. Fam Pract 1997; 14: 1 17-23.
Meliala L. Aspek psikososial epilepsi. Simposium
penatalaksanaan mutakhir epilepsi. Yogyakarta;
1992.
Brodie MJ, Dichter MA. Antiepileptic drugs. N
Engl J Med 1996; 334: 168-75.
Smith D, Chadwick D. The management of
epilepsy. J Neurol Neurosurg Psychiatry 2001 ; 70:
ii 1 5 4 21.
Harsono. Epilepsi. 1" ed. Yogyakarta: Gadjah Mada
University Press, 200 1.
Dreifuss FE. Prognosis of childhood seizure
disorders: present and future. Epilepsia 1994; 35
(suppl2): S30-S4.
Sadzot B. Epilepsy: a progressive disease? Br Med
J 1997; 314: 91.
Morrell F. Secondary epileptogenesis in man. Arch
Neurol 1985; 42: 3 18-35.
Holmes GL. Epilepsy in the developing brain:
lessons fiom the laboratory and clinic. Epilepsia
1997; 38: 12-30.
Page RM, Cole GE, Timmreck TC. Basic
epidemiological methods and biostatistics. A
practical guide book. London: Jones and Bartlet
Publisher; 1996.
Carpay HA, Arts WFM, Geerts AT, Stroink .H.
Epilepsy in childhood: an audit of clinical practice.
Arch Neurol 1998; 55: 668-73.
Chapman AG. Glutamate and epilepsy, glutamate
and glutamine in the brain. J Nutr 2000; 130:
1043s-45s.
Holmes GL, Ben-Ari Y. The neurobiology and
consequences of epilepsy in developing brain.
Pediatr Res 200 1;49: 320-5.
Fong GCY. Fong JKY. Recent advances in the
diagnosis and management of epilepsy. Hong Kong
Med J 2001; 7: 73-84.
Browne TR. Holmes GL. Handbook of epilepsy,
2"ded. New York: Lippincott Williams; 2000.
Kulkarini SK. George B. Significance on long term
potentiation (LTP) in cognitive functions and
epilepsy. Indian J Pharmacother 1999; 3 1: 14-22.
Lowenstein DH. Alldredge BK. Status epilepticus.
N Engl J Med 1998; 338: 970-6.
Reynolds EH. Controversies in management: do
anticonwlsants alter the natural course of epilepsy?
Treatment should be started as early as possible.
Br Med J 1995; 3 10: 176-7.
Carnfield C, Camfield P, Gordon K, Dooley J. Does
the number of seizures before treatment influence
ease ofcontrol or remission of childhood epilepsy?
not if the number is 10 or less. Neurology 1996;
46: 41-4.
Kwan P, Brodie MJ. Early identification of
refractory epilepsy. N Engl J Med 2000; 342: 3149.
Cockerell OC, Johnson AL, Sander JWAS, Shorvon
SD. Prognosis of epilepsy: a review and further
analysis ofthe first nine years ofthe british national
general practice study of epilepsy. A prospective
population based study. Epilepsia 1997; 38: 3 146.
Arts WFM, Geerts AT, Brouwer OF, Peters ACB,
Stroink H, Donselaar CAV. The early prognosis of
epilepsy in childhood: the prediction of poor
outcome. The Dutch study of epilepsy in childhood.
Epilepsia 1999; 40: 726-34.
Sperling MR, Bucurescu G, Kim B. Epilepsy
management: issues in medical and surgical
treatment. Postgrad Med 1997; 102: 1.
Permca E, Beghi E, Dulac 0 , Shorvon S, Tomson
T. Assesing risk to benefit ratio in antiepileptic
drug therapy. Epilepsy Res 2000; 41: 107-39.
Berg AT, Shimar S, Levy SR, Testa FM, Rapaport
SS, Beckerman B, et al. Two year remission and
subsequent relapse in children with newly
diagnosed epilepsy. Epilepsia 200 1; 44: 1553-62.
Gilad R,Lamp1 Y, Gabbay V, Eshel Y, Pinhas IS.
Early treatment of a single generalized tonic clonic
seizure to prevent recurrence. Arch Neurol 1996;
53: 1149-52.
Singhvi JP, Sawhney IMS, Lai V, Pathak A,
Prabhakar S. Profile of intractable epilepsy in a
tertiary refereal centre. Neurol India 2000; 48: 35 16.
Placencia JG. Epilepsy in childhood, brain and
mind magazine, State University of Campinas,
Brazil; 1997.
Cavazos JE, Lum F, Spitz M. Seizure and epilepsy:
overview and classification. Med J 2002; 4: 3.
Beydoun A, Passaro EA. Appropriate use of
medications for seizures: guiding principles on the
path of efficacy. Postgrad Med 2002; 111: 69-82.
Kyngas H. Predictors of good compliance in
adolescents with epilepsy. Seizure 2001; 10: 5493.