HIGH IL-1RA PLASMA LEVEL AS PROTECTIVE FACTOR IN BALINESE CHILDREN WITH IDIOPATHIC GENERALIZED EPILEPSY.
HIGH IL-1RA PLASMA LEVEL AS PROTECTIVE FACTOR IN BALINESE
CHILDREN WITH IDIOPATHIC GENERALIZED EPILEPSY
1Anna
Marita Gelgel., 2A.A.G.Sudewa Djelantik., 3Thomas Eko Purwata, 4Junita
1
Department of Neurology Faculty of Medicine Udayana University,Bali-Indonesia
2
Department of Clinical Pathology Faculty of Medicine Udayana University, Bali-Indonesia
3
Department of Neurology Faculty of Medicine Udayana University,Bali-Indonesia
4
Department of Biology Udayana University, Bali-Indonesia
Abstract
Idiopathic generalized epilepsies (IGEs) are the commonest group of epilepsies in children
and adolescents. Their type and characteristic of syndromes follow the classification of The
International League Against Epilepsy (ILAE) 1989. (1) Seizures as the hallmark of the syndromes
resulted from the imbalance between excitatory and inhibitory neurotransmitter.(2).
IL-1RA is an inhibitory neurotransmitter that counter act the function of IL-1 and stimulate
after the expression of IL-1
plasma. This study was aimed to investigate the plasma level of
IL-1RA using standard Elisa method in Balinese children with IGEs (25 pateinets) compare to
Balinese children withou IGEs (25 helathy children). They were matched for age and sex and met
inclusion and exclusion criterions. The results was (with Mc-Nemar test) high IL-1RA plasma
level in Balinese children with IGEs have significantly relationship ( p=0,013) with OR 0,214
(CI 95%=0,059-0,458), and have protective factor of 0,214 times in prevention the development
of seizures in Balinese children with IGEs.
Key words; IGEs, IL-1RA, Elisa test.
1
Introduction
Idiopathic generalized epilepsies (IGEs) are a distinct group of epilepsies, clearly defined in the
1989 International Classification of Epileptic Syndromes and Epilepsies of International Legue
Against Epilepsy. This classification established an important dichotomy between the idiopathic
epilepsies on the one hand, and the symptomatic or cryptogenic epilepsies on the other1
Although it is now clearly understood that IGEs are primarily of genetic origin, the
observations about this disorders still on progress. In the twentieth century, epileptologists all over
the world have conducted many experiments with animal models of epilepsy and human
specimens from temporal lobe epilepsy (TLE). They found that in epileptic events there are
evidences of inflammation play an important role and some cytokines such as excitatory and
inhibitory neurotransmitters significantly found in plasma in acute phase following seizures with
greater level than normally situations.1,2
The IGEs constitute approximately 15–20% of all epilepsies. They affect all races equally and
may have a slight predilection for women. Seizures usually, but not always, have an onset early
in life, from childhood to early adulthood. In fact, IGEs are the most frequent group of epilepsies
with an adolescent onset.2
Interleukin-1β (IL-1β) significantly exacerbates seizure activity when intracerebrally injected
in rodents shortly before the induction of hippocampal seizures or SE. On the contrary, Interleukin
1 Receptor Antagonist (IL-1RA), a naturally occurring molecule that antagonizes the effect of
endogenous IL-1β, has powerful anticonvulsant activity, and IL-1RA over expressing mice display
a reduced susceptibility to seizures. However, the role of IL-1RA in disease, pathogenesis, and the
relationship between host protection and disease remains unclear.2
2
IL-1RA is structurally related to IL-1α and IL-1β and competes with these molecules for
occupation of IL1 cell surface receptors. The presence of the IL-1RA allele II was ascociated with
enhanced IL-1β production in vitro. The results further suggest that the IL-1RA allele II as well as
the increased production of IL-1β might play a role in preventing febrile convulsions.3
Study of IL-1RA where intrahippocampal application of recombinant IL-1RA or its selective
endogenous overexpression in astrocytes under the control of glial acidic fibrillary protein
promoter potentially inhibits motor and electroencephalographic seizures induced by bicuculline
methiodide in mice. This resulys demonstrate that IL-1RA mediates potent anticonvulsant effects
acting on IL-1R type I and suggest that the balance between brain IL-1β and IL-1RA represents a
crucial mechanism to control seizure generalization.4
In the present study, we therefore aimed to determine whether IL-1RA high plasma level in
Balinese children with IGE has protective factor.
Material and Methods.
Clnical Procedures
All subjects were of Balinese children with IGEs (25 patients) and control individuals (25 helathy
Balinese children) without IGs that were recruited consecutively from some hospitals around
Denpasar, Bali. The study protocol was approved by the Ethics Committee of Medical Faculty of
Udayana University/ Sanglah Hospital. Subjects participated in the study after providing informed
consent and being advised about their disease. Evaluation of each participant consisted of personal
and family medical histories, neurological examinations, and some metabolic tests. Exclusion
criteria for both groups were as follows; no history of under corticosteroid medications, no fever,
no sign of infections, no metabolic disturbances.
3
Sample collection
Venepuncture was performed to collect 3 ml peripheral blood from each subject into tubes and
were left to clot in room temperature for about 30 minutes and then were centrifuged at 3000 RPM
for 15 minutes. The level of IL-1RA was analysed using Elisa method in pg/ml. The cut off point
for the highest level of IL-1RA was determined by using ROC curve since there has no data for
IL-1RA level in Balinese children with IGE neither in Balinese healthy children.
Results
Twenty five Balinese children with IGE and twenty five healthy Balinese children were recruited
and their characteristics were shown in table 1.
Table 1. The Characteristic of subjects
Characteristic
Age (months)
Minimal (months)
Maximal (months)
Sex
Male
Female
Onset of seizure
> 4 days
< 4 days
No seizures
Family history
Aunty (mother)had seizure
Father had seizure
Mother had seizure
Aunty (father) had seizure
Grand mother had seizure
No seizures
Case (n= 25)
101,04±47,99
10
204
control (n= 25)
105,12±52,34
12
204
18 (72)
7 (18)
18 (72)
7 (18)
19 (76)
6 (24)
0 (0)
0 (0)
0 (0)
25 (100)
1 (4)
5 (20)
2 (8)
2 (8)
0 (0)
0 (0)
0 (0)
0 (0)
1 (4)
14 (56)
0 (0)
25 (100)
4
Each group consisted 18 males and 7 females with the rate of age in subjects group was
101,04±47,99 months with the youngest of 10 months and the oldest was 204 months versus in
control group with the rate of age was 105,12±52,34 months with the youngest age was 12 months
and the oldest was 204 months.
Abnormal distribution was found from case group which with onset of seizure to time of
examination >4 days were 19 patients versus 50-60% very weak, >60-70% weak, >70-80%
moderate, >80-90% fair, >90-100% good. From the ROC curve analysis we found that area under
the curve the results of IL-1RA level was 0,278 (CI 95%; 0,130-0,426) with p value=0,007.
Diagnostic examination with AUC was 0,278 which meant that if the examination was brought to
100 patients then will have the right conclusions in deciding whether there is a disease for only
around 27,8%. Based on this, we found that 436,75 was the best cut off point for evaluation IL1RA level in plasma with sensitivity 76% and spesifitivity 56%. Based on this optimum value
border we divided the IL-1RA level into two groups of hingh level IL-1RA if the level was >
436,75 pg/ml and normal level was ≤ 436,75 pg/ml. we studied the relationship between two group
with Mc-Nemar test and the result is shown in table 4. dihubungkan dengan kedua kelompok
kasus dan kontrol. Hasilnya akan terlihat pada tabel berikut.
Table 4. cross tabulation between IL-1 RA levels of two groups
control
IL-1RA
high
case
IL-1RA
high
4 (22,2)
(%)
IL-1RA
normal 14 (77,8)
(%)
Total
18 (100)
n (%)
IL-1RA
normal
P
value
CI 95%
OR
lower
border
upper
border
0,059
0,458
3 (42,9)
0,013
0,214
4 (57,1)
7 (100)
This study found that high level IL-1RA (Mc-Nemar test) have significant relationship with
p=0,013 with OR; 0,214 (CI 95%=0,059-0,458), that is meant that high IL-1RA level has the
protective factor 0,214 times to prevent the excisting of seizures in the case group.
7
Discussion
IGEs have cumulative incidence of approximately 0,7% in the general population; they
account for about 40% of all epilepsies up to age 40 and have a general frequency of around 1520% of all epilepsies.1 There is no data for the IGE incidence in Bali, but from age characteristic
this study revealed that the youngest age was 10 months while the oldest was 18 years old.
This study also showed that male (18 pateints/ 72%) more affected than female (7
patients/18%). For most but not all incidence studies, sex-specific differences in incidence are not
statistically significant. 5
From the onset of seizures until patients seeking medical advice we divided into two
groups; group with 4 days. It is based on the level of IL-1RA in plasma that
reaches it”s highest level at 4th day of the seizure and will be dereased after 4th day. The expression
of IL-1RA depends on the expression of IL-1 and maximum level of IL-1 is around the 4th day
and tend to decrease after it.6
It has been estimated that genetic factors contribute to at least 40% of all epilepsies as
mendelian modes of inheritance. Mothers transmitted the disorder to their offspring. In this study
we found that 5 (20%) fathers had seizure versus 2 (8%) mothers had seizures; 2 (8%) aunties
(from father’s side) and 1 (4%) aunty (from mother’s side), 1 (4%) grand mother has seizure and
14 (56%) patients IGEs without seizures.7
The rate of level IL-1RA was 560,33±360,76 with 25 percentile of 325,85, median 420,7
with 75 percentile of 721,90. The rate of IL-RA was 427,07±178,97 (case group), with 25
percentile of 325,60, median 365,40 and 75 percentile of 476,05. From control group the rate of
IL-1RA was 721,59±428,99, with 25 percentile of 389,70, median 600,10 and 75 percentile of
936,20. All data has normal spread. The IL-1RA level in case group were found higher compare
8
to control group. To see whether there was any difference between the two group, we made a pair
t test as showed in table 3 that the differences rate of IL-1RA level in two groups where in case
group it had higher IL-1RA level compare to the case group. To evaluate the relationship between
the rate of IL-1RA with the occurance of seizures we use pair t test and the result was found
significantly different between two group (p=0,007). The next step we used ROC table to stated
the optimal border value. The set a cut off point in IL-1RA level, we used receiver operating
characteristic (ROC) based on sensitivity and specificity value in a very optimal one based on ROC
analysis. The ROC curve connected sensitivity value and 1-specificity. Area under curve is used
to calculate diagnose accuracy. The diagonal line consists of sensitivity value=1-specificity. The
closer the ROC curve to diagonal line, the worst the result. The best of the cut off point is the
longest far left from normal line. The AUC value interpretation are; >50-60% very weak, >6070% weak, >70-80% moderate, >80-90% fair, >90-100% good. From the ROC curve analysis
we found that area under the curve the results of IL-1RA level was 0,278 (CI 95%; 0,130-0,426)
with p value=0,007. Diagnostic examination with AUC was 0,278 which meant that if the
examination was brought to 100 patients then will have the right conclusions in deciding whether
there is a disease for only around 27,8%. Based on this, we found that 436,75 was the best cut off
point for evaluation IL-1RA level in plasma with sensitivity 76% and spesifitivity 56%. Based on
this optimum value border we divided the IL-1RA level into two groups of hingh level IL-1RA if
the level was > 436,75 pg/ml and normal level was ≤ 436,75 pg/ml. we studied the relationship
between two group with Mc-Nemar test and the result is shown in table 4. This study found that
high level IL-1RA (Mc-Nemar test) have significant relationship with p=0,013 with OR; 0,214
(CI 95%=0,059-0,458), that is meant that high IL-1RA level has the protective factor 0,214 times
to prevent the excisting of seizures in the case group as it’s act merely to counter of excitatory
9
effect of IL-1 . In some studies in different disease the researches also showed the same results.
8, 9,10
References
1.Guerrini R, Shorvon SD, Andermann F, Andermann E. 2011. Introduction to the concept of genetic
epilepsy. In: Shorvon SD, Andermann F, Guerrini R. eds. The causes of epilepsy. Common and
uncommon causes in adults and children. Cambridge university press.UK;43-58
2.Vezzani AM., Peltola J, Janigor D. Inflammation. 2008. In: Engel J, Pedley.T.eds. Epilepsy. A
comprehensive Textbook. 2nd edition. Lippincott William & Wilkins. Philadelphia. 267-274
3. Jarrot B, Aprico A. 2010. Microglia: protective and pathogenic mediators.In: Kilpatrick T, Ransohoff
RM, Wesselingh S.eds. Inflammatory diseases of the central nervous system. Cambridge Univ
press.2010:21-24
3.Tsai FJ, Hsieh YY, chang CC, Lin CC, Tsai CH. 2002. Polymorphisms for interleukin 1b exon 5 and
interleukin 1 recepyor antagonist in Taiwanese children with febrile convulsions. Arch Pediatr adolesc
med.(156):545-8.
4.vezzani A, Moneta D, Conti M, Richichi C, Raviza T, Luigi AD, De simony MG, Sperks G, Jonsson J.
2000. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic
overexpression in mice. The Salk Institute for biological studies, La Jolla.
5.Banerjee PN, Hauser WA.2008. Incidence and prevalence.In; Engel J, Padley T. Engel J, Pedley.T.eds.
Epilepsy. A comprehensive Textbook. 2nd edition. Lippincott William & Wilkins. Philadelphia; 39-43
6.Lukasiuk Lukasiuk K., , Dingledine R., Lowenstein DH., Pitkonen A. 2008; Gene Expression Underlying
Changes in Network Excitability. In: Engel, J.ed. Epilepsy. A Comprehensive Textbook.2nd edition.
Lippincott Williams & Wilkins. Philadelphia. 307-19
7.
Berkovic
S.
Epilepsy
Reseach
Group.
Clinical
Genetic.
www.austinmedicine.unimelb.edu.au/research/epilepsy. download April 22nd 2014.
Availb
from;
8. Steinlein OK. 2001. Genes and mutations in idiopathic epilepsy. Am J Med. Genet, 106(2):139-45
9..McGeer PL, Schuizer M. McGeer EG. 1996. Arthritis and anti-inflammatory agents as possible
protective factors for Alzheimer’s disease. J Neurology vol 47:452-432
10.Touzani O, Boutin H, LeFeuvre R, Parker L, Miller A, Luheshi G, Rothwel N. 2002. Interleukin-1
influences ischemic brain damage in the mouse independentof the Interleukin-1 type receptor. J of
neuroscience vol 22(1):38-43
10
CHILDREN WITH IDIOPATHIC GENERALIZED EPILEPSY
1Anna
Marita Gelgel., 2A.A.G.Sudewa Djelantik., 3Thomas Eko Purwata, 4Junita
1
Department of Neurology Faculty of Medicine Udayana University,Bali-Indonesia
2
Department of Clinical Pathology Faculty of Medicine Udayana University, Bali-Indonesia
3
Department of Neurology Faculty of Medicine Udayana University,Bali-Indonesia
4
Department of Biology Udayana University, Bali-Indonesia
Abstract
Idiopathic generalized epilepsies (IGEs) are the commonest group of epilepsies in children
and adolescents. Their type and characteristic of syndromes follow the classification of The
International League Against Epilepsy (ILAE) 1989. (1) Seizures as the hallmark of the syndromes
resulted from the imbalance between excitatory and inhibitory neurotransmitter.(2).
IL-1RA is an inhibitory neurotransmitter that counter act the function of IL-1 and stimulate
after the expression of IL-1
plasma. This study was aimed to investigate the plasma level of
IL-1RA using standard Elisa method in Balinese children with IGEs (25 pateinets) compare to
Balinese children withou IGEs (25 helathy children). They were matched for age and sex and met
inclusion and exclusion criterions. The results was (with Mc-Nemar test) high IL-1RA plasma
level in Balinese children with IGEs have significantly relationship ( p=0,013) with OR 0,214
(CI 95%=0,059-0,458), and have protective factor of 0,214 times in prevention the development
of seizures in Balinese children with IGEs.
Key words; IGEs, IL-1RA, Elisa test.
1
Introduction
Idiopathic generalized epilepsies (IGEs) are a distinct group of epilepsies, clearly defined in the
1989 International Classification of Epileptic Syndromes and Epilepsies of International Legue
Against Epilepsy. This classification established an important dichotomy between the idiopathic
epilepsies on the one hand, and the symptomatic or cryptogenic epilepsies on the other1
Although it is now clearly understood that IGEs are primarily of genetic origin, the
observations about this disorders still on progress. In the twentieth century, epileptologists all over
the world have conducted many experiments with animal models of epilepsy and human
specimens from temporal lobe epilepsy (TLE). They found that in epileptic events there are
evidences of inflammation play an important role and some cytokines such as excitatory and
inhibitory neurotransmitters significantly found in plasma in acute phase following seizures with
greater level than normally situations.1,2
The IGEs constitute approximately 15–20% of all epilepsies. They affect all races equally and
may have a slight predilection for women. Seizures usually, but not always, have an onset early
in life, from childhood to early adulthood. In fact, IGEs are the most frequent group of epilepsies
with an adolescent onset.2
Interleukin-1β (IL-1β) significantly exacerbates seizure activity when intracerebrally injected
in rodents shortly before the induction of hippocampal seizures or SE. On the contrary, Interleukin
1 Receptor Antagonist (IL-1RA), a naturally occurring molecule that antagonizes the effect of
endogenous IL-1β, has powerful anticonvulsant activity, and IL-1RA over expressing mice display
a reduced susceptibility to seizures. However, the role of IL-1RA in disease, pathogenesis, and the
relationship between host protection and disease remains unclear.2
2
IL-1RA is structurally related to IL-1α and IL-1β and competes with these molecules for
occupation of IL1 cell surface receptors. The presence of the IL-1RA allele II was ascociated with
enhanced IL-1β production in vitro. The results further suggest that the IL-1RA allele II as well as
the increased production of IL-1β might play a role in preventing febrile convulsions.3
Study of IL-1RA where intrahippocampal application of recombinant IL-1RA or its selective
endogenous overexpression in astrocytes under the control of glial acidic fibrillary protein
promoter potentially inhibits motor and electroencephalographic seizures induced by bicuculline
methiodide in mice. This resulys demonstrate that IL-1RA mediates potent anticonvulsant effects
acting on IL-1R type I and suggest that the balance between brain IL-1β and IL-1RA represents a
crucial mechanism to control seizure generalization.4
In the present study, we therefore aimed to determine whether IL-1RA high plasma level in
Balinese children with IGE has protective factor.
Material and Methods.
Clnical Procedures
All subjects were of Balinese children with IGEs (25 patients) and control individuals (25 helathy
Balinese children) without IGs that were recruited consecutively from some hospitals around
Denpasar, Bali. The study protocol was approved by the Ethics Committee of Medical Faculty of
Udayana University/ Sanglah Hospital. Subjects participated in the study after providing informed
consent and being advised about their disease. Evaluation of each participant consisted of personal
and family medical histories, neurological examinations, and some metabolic tests. Exclusion
criteria for both groups were as follows; no history of under corticosteroid medications, no fever,
no sign of infections, no metabolic disturbances.
3
Sample collection
Venepuncture was performed to collect 3 ml peripheral blood from each subject into tubes and
were left to clot in room temperature for about 30 minutes and then were centrifuged at 3000 RPM
for 15 minutes. The level of IL-1RA was analysed using Elisa method in pg/ml. The cut off point
for the highest level of IL-1RA was determined by using ROC curve since there has no data for
IL-1RA level in Balinese children with IGE neither in Balinese healthy children.
Results
Twenty five Balinese children with IGE and twenty five healthy Balinese children were recruited
and their characteristics were shown in table 1.
Table 1. The Characteristic of subjects
Characteristic
Age (months)
Minimal (months)
Maximal (months)
Sex
Male
Female
Onset of seizure
> 4 days
< 4 days
No seizures
Family history
Aunty (mother)had seizure
Father had seizure
Mother had seizure
Aunty (father) had seizure
Grand mother had seizure
No seizures
Case (n= 25)
101,04±47,99
10
204
control (n= 25)
105,12±52,34
12
204
18 (72)
7 (18)
18 (72)
7 (18)
19 (76)
6 (24)
0 (0)
0 (0)
0 (0)
25 (100)
1 (4)
5 (20)
2 (8)
2 (8)
0 (0)
0 (0)
0 (0)
0 (0)
1 (4)
14 (56)
0 (0)
25 (100)
4
Each group consisted 18 males and 7 females with the rate of age in subjects group was
101,04±47,99 months with the youngest of 10 months and the oldest was 204 months versus in
control group with the rate of age was 105,12±52,34 months with the youngest age was 12 months
and the oldest was 204 months.
Abnormal distribution was found from case group which with onset of seizure to time of
examination >4 days were 19 patients versus 50-60% very weak, >60-70% weak, >70-80%
moderate, >80-90% fair, >90-100% good. From the ROC curve analysis we found that area under
the curve the results of IL-1RA level was 0,278 (CI 95%; 0,130-0,426) with p value=0,007.
Diagnostic examination with AUC was 0,278 which meant that if the examination was brought to
100 patients then will have the right conclusions in deciding whether there is a disease for only
around 27,8%. Based on this, we found that 436,75 was the best cut off point for evaluation IL1RA level in plasma with sensitivity 76% and spesifitivity 56%. Based on this optimum value
border we divided the IL-1RA level into two groups of hingh level IL-1RA if the level was >
436,75 pg/ml and normal level was ≤ 436,75 pg/ml. we studied the relationship between two group
with Mc-Nemar test and the result is shown in table 4. dihubungkan dengan kedua kelompok
kasus dan kontrol. Hasilnya akan terlihat pada tabel berikut.
Table 4. cross tabulation between IL-1 RA levels of two groups
control
IL-1RA
high
case
IL-1RA
high
4 (22,2)
(%)
IL-1RA
normal 14 (77,8)
(%)
Total
18 (100)
n (%)
IL-1RA
normal
P
value
CI 95%
OR
lower
border
upper
border
0,059
0,458
3 (42,9)
0,013
0,214
4 (57,1)
7 (100)
This study found that high level IL-1RA (Mc-Nemar test) have significant relationship with
p=0,013 with OR; 0,214 (CI 95%=0,059-0,458), that is meant that high IL-1RA level has the
protective factor 0,214 times to prevent the excisting of seizures in the case group.
7
Discussion
IGEs have cumulative incidence of approximately 0,7% in the general population; they
account for about 40% of all epilepsies up to age 40 and have a general frequency of around 1520% of all epilepsies.1 There is no data for the IGE incidence in Bali, but from age characteristic
this study revealed that the youngest age was 10 months while the oldest was 18 years old.
This study also showed that male (18 pateints/ 72%) more affected than female (7
patients/18%). For most but not all incidence studies, sex-specific differences in incidence are not
statistically significant. 5
From the onset of seizures until patients seeking medical advice we divided into two
groups; group with 4 days. It is based on the level of IL-1RA in plasma that
reaches it”s highest level at 4th day of the seizure and will be dereased after 4th day. The expression
of IL-1RA depends on the expression of IL-1 and maximum level of IL-1 is around the 4th day
and tend to decrease after it.6
It has been estimated that genetic factors contribute to at least 40% of all epilepsies as
mendelian modes of inheritance. Mothers transmitted the disorder to their offspring. In this study
we found that 5 (20%) fathers had seizure versus 2 (8%) mothers had seizures; 2 (8%) aunties
(from father’s side) and 1 (4%) aunty (from mother’s side), 1 (4%) grand mother has seizure and
14 (56%) patients IGEs without seizures.7
The rate of level IL-1RA was 560,33±360,76 with 25 percentile of 325,85, median 420,7
with 75 percentile of 721,90. The rate of IL-RA was 427,07±178,97 (case group), with 25
percentile of 325,60, median 365,40 and 75 percentile of 476,05. From control group the rate of
IL-1RA was 721,59±428,99, with 25 percentile of 389,70, median 600,10 and 75 percentile of
936,20. All data has normal spread. The IL-1RA level in case group were found higher compare
8
to control group. To see whether there was any difference between the two group, we made a pair
t test as showed in table 3 that the differences rate of IL-1RA level in two groups where in case
group it had higher IL-1RA level compare to the case group. To evaluate the relationship between
the rate of IL-1RA with the occurance of seizures we use pair t test and the result was found
significantly different between two group (p=0,007). The next step we used ROC table to stated
the optimal border value. The set a cut off point in IL-1RA level, we used receiver operating
characteristic (ROC) based on sensitivity and specificity value in a very optimal one based on ROC
analysis. The ROC curve connected sensitivity value and 1-specificity. Area under curve is used
to calculate diagnose accuracy. The diagonal line consists of sensitivity value=1-specificity. The
closer the ROC curve to diagonal line, the worst the result. The best of the cut off point is the
longest far left from normal line. The AUC value interpretation are; >50-60% very weak, >6070% weak, >70-80% moderate, >80-90% fair, >90-100% good. From the ROC curve analysis
we found that area under the curve the results of IL-1RA level was 0,278 (CI 95%; 0,130-0,426)
with p value=0,007. Diagnostic examination with AUC was 0,278 which meant that if the
examination was brought to 100 patients then will have the right conclusions in deciding whether
there is a disease for only around 27,8%. Based on this, we found that 436,75 was the best cut off
point for evaluation IL-1RA level in plasma with sensitivity 76% and spesifitivity 56%. Based on
this optimum value border we divided the IL-1RA level into two groups of hingh level IL-1RA if
the level was > 436,75 pg/ml and normal level was ≤ 436,75 pg/ml. we studied the relationship
between two group with Mc-Nemar test and the result is shown in table 4. This study found that
high level IL-1RA (Mc-Nemar test) have significant relationship with p=0,013 with OR; 0,214
(CI 95%=0,059-0,458), that is meant that high IL-1RA level has the protective factor 0,214 times
to prevent the excisting of seizures in the case group as it’s act merely to counter of excitatory
9
effect of IL-1 . In some studies in different disease the researches also showed the same results.
8, 9,10
References
1.Guerrini R, Shorvon SD, Andermann F, Andermann E. 2011. Introduction to the concept of genetic
epilepsy. In: Shorvon SD, Andermann F, Guerrini R. eds. The causes of epilepsy. Common and
uncommon causes in adults and children. Cambridge university press.UK;43-58
2.Vezzani AM., Peltola J, Janigor D. Inflammation. 2008. In: Engel J, Pedley.T.eds. Epilepsy. A
comprehensive Textbook. 2nd edition. Lippincott William & Wilkins. Philadelphia. 267-274
3. Jarrot B, Aprico A. 2010. Microglia: protective and pathogenic mediators.In: Kilpatrick T, Ransohoff
RM, Wesselingh S.eds. Inflammatory diseases of the central nervous system. Cambridge Univ
press.2010:21-24
3.Tsai FJ, Hsieh YY, chang CC, Lin CC, Tsai CH. 2002. Polymorphisms for interleukin 1b exon 5 and
interleukin 1 recepyor antagonist in Taiwanese children with febrile convulsions. Arch Pediatr adolesc
med.(156):545-8.
4.vezzani A, Moneta D, Conti M, Richichi C, Raviza T, Luigi AD, De simony MG, Sperks G, Jonsson J.
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